On June 1, 2026 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a transformative pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies broadly to patients with cancer and autoimmune diseases, reported clinical data this weekend featuring its off-the-shelf CAR T-cell program FT836 at the American Society of Cancer Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago, IL, May 29 – June 2, 2026.

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"Early Phase 1 data for FT836 represents a truly exciting moment for patients with certain advanced solid tumors who have exhausted their treatment options" said Bob Valamehr, Ph.D., MBA, President and Chief Executive Officer of Fate Therapeutics. "In this preliminary stage of the study, we are seeing notable tumor reduction in KRASwt metastatic colorectal cancer patients after treatment with FT836, an observation that did not require conditioning chemotherapy with the inclusion of our Sword and Shield technology. This novel 9-point edited CAR T-cell product candidate is uniformly manufactured from a single clonal master cell bank, meaning we can produce FT836 at massive scale with consistency and have it available off-the-shelf and on-demand for broad access for cancer patients with unmet need. We believe FT836 has the potential to fundamentally change how solid tumor treatment is approached, especially in combination with standard-of-care therapies. We look forward to continuing to build on these early results as enrollment expands in the FT836 study."

Presentation Summary Includes:

Title: Preliminary Phase 1 Results of a MICA/B-targeted CAR T cell Designed to Overcome Solid Tumor Escape Mechanisms and Avoid the Requirement for Conditioning Chemotherapy

As of the April 20, 2026 data cutoff, nine patients have been enrolled across two regimens (Regimen C: FT836 + cetuximab, n=6 and Regimen E: FT836 + trastuzumab, n=3) with all patients evaluated for safety, and five available for initial efficacy assessment: (Regimen C, n=4 and Regimen E , n=1). Both regimens are administered without conditioning chemotherapy. Key findings include:

Favorable safety profile with no dose-limiting toxicities (DLTs), cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft versus host disease (GvHD) observed across any patient or dose level for all nine patients.
First-in-human evidence of FT836 trafficking to and persisting within tumor tissue without the use of conditioning chemotherapy, along with evidence of remodeling of the tumor immune microenvironment.
Preliminary anti-tumor activity in the two efficacy-evaluable heavily pre-treated KRAS wild-type (KRASwt) metastatic colorectal cancer (mCRC) patients, each with seven prior lines of therapy, including meaningful reductions in target lesion size and significant decreases in tumor biomarker expression, including carcinoembryonic antigen (CEA) expression. Based on these promising results, the Company plans to focus on this CRC patient population.

Sword and Shield Technology Facilitates CAR T-cell Activity without the Need for Conditioning Chemotherapy

FT836 incorporates Sword and Shield technology—a coordinated dual-engineering strategy designed to eliminate the need for lymphodepleting conditioning chemotherapy. The Sword component, an alloimmune-defense receptor (ADR), enables FT836 to selectively recognize and eliminate alloreactive host immune cells, including T cells, that would otherwise reject the allogeneic product. The Shield component, deletion of CD58, renders FT836 resistant to host immune cell surveillance, further supporting functional persistence of FT836. In previously presented preclinical data, these elements together enabled ~20–30x improvement in in vivo persistence in various allogeneic mouse models and ~5x selective containment of product-specific host immune responses, supporting the planning of clinical strategies without conditioning chemotherapy—a critical differentiator for patient tolerability and access.

FT836 Persistence in the Periphery and Tumor Tissue

A critical translational finding from this study is the first-in-human detection of FT836 in both peripheral blood and tumor tissue without conditioning chemotherapy. Using multi-parameter flow cytometry, FT836 cells were detected in the peripheral blood of patients with an intact host immune system following first dose, peaking at Day 4 and persisting for approximately another week. Strikingly, FT836 was subsequently detected in patient tumor biopsy at Day 22 by transgene-targeted RNAscope, which is well beyond their detection in the periphery, suggestive of efficient trafficking to tumor-bearing tissue and markedly prolonged tissue persistence relative to blood. This extended tissue residence, supported by CXCR2 trafficking receptor and TGFβ signal redirect receptor engineered into FT836, was accompanied by meaningful remodeling of the tumor immune microenvironment. Immunohistochemistry imaging from liver biopsy revealed that CD8+ T cells, which were spatially excluded from the tumor at baseline, were found adjacent to and in direct contact with tumor cells on-study; evidence of treatment-associated activation and recruitment of endogenous anti-tumor immunity.

Clinical Case Studies: Broad expression of MICA/B antigen and Anti-Tumor Activity in KRASwt Metastatic Colorectal Cancer

Screening biopsies from both patients confirmed broad expression of MICA/B and EGFR target antigens on tumor cells, validating the multi-antigen targeting rationale of FT836 plus cetuximab in mCRC.

Case 1: Regimen C DL1 — 19% Tumor Reduction; All target lesions reduced; 62% CEA Decline

A 45-year-old male with KRASwt metastatic CRC and lung, bone, and nodal disease received FT836 at 300 million cells/dose on Days 1 and 15 with cetuximab (no conditioning chemotherapy), following seven prior lines of therapy including prior cetuximab.

CEA tumor marker decreased from 487 ng/mL at screening to 185 ng/mL by Day 56 (62% reduction).
All RECIST target lesions decreased in size; overall 19% reduction in sum of diameters (70 mm → 55 mm) across lung and nodal lesions.
No FT836-related adverse events observed.

Case 2: Regimen C DL2 — 52% Liver Lesion Reduction; Stable Disease; Pain associated with tumor Resolved

A 53-year-old male with KRASwt metastatic CRC involving lung, liver, adrenal, and nodal disease received FT836 at 900 million cells/dose on Days 1, 8, and 15 with cetuximab (no conditioning chemotherapy), following seven prior lines of therapy including multiple cetuximab-containing regimens.

A liver target lesion demonstrated a 52% reduction in diameter; RECIST-assessed stable disease confirmed post data cutoff.
Cancer antigen (CA)19-9 decreased from 258 to 144 by Day 56 (44% reduction).
Tumor-related pain resolved during treatment.
No FT836-related adverse events observed.
About FT836

FT836 is the Company’s multipoint-edited CAR T-cell product candidate uniquely targeting major histocompatibility complex (MHC) proteins A (MICA) and B (MICB). The expression of MICA/B cell-surface proteins is induced by cellular stress or malignant transformation and is detectable across many types of cancer cells with limited expression on healthy tissue. At the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 40th Annual meeting held in November 2025, the Company presented preclinical data showing FT836 exhibited potent and durable CAR-dependent antigen-driven proliferation with robust activity across diverse solid tumors and that FT836 can be combined with standard of care chemotherapy to induce MICA/B surface expression for enhanced target recognition and additive antitumor activity. In addition, the Company presented immunohistochemistry analysis showing that MICA/B is expressed throughout tumor tissue in biopsy samples obtained from patients with various cancers, including colorectal cancer. FT836 is also the Company’s first product candidate to incorporate the novel Sword & ShieldTM technology, which utilizes the Company’s novel alloimmune defense receptor (ADR) alongside CD58 knockout (KO), to both target and evade host alloreactive immune cells for a comprehensive strategy to avoid the need for conditioning chemotherapy. In January 2025, the Company secured a $4 million award from the California Institute of Regenerative Medicine (CIRM) to support IND-enabling activities for FT836.

(Press release, Fate Therapeutics, JUN 1, 2026, View Source [SID1234666303])

On June 1, 2026 Convergent Therapeutics Inc., a clinical-stage biotechnology company developing next-generation radiopharmaceuticals for the treatment of cancer, reported interim data from Part 3 of its Phase 2 CONVERGE-01 study of Ac-225 rosopatamab tetraxetan (CONV01-α) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with Lu-177-PSMA radioligand therapy (Lu-PSMA). In the study, CONV01-α demonstrated promising anti-tumor activity, emerging durability, and a highly favorable tolerability profile, with clinically-manageable hematologic toxicity at the target dose and no renal toxicity or high-grade xerostomia (dry mouth).

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These data support Convergent’s plan to advance CONV01-α toward a pivotal Phase 3 study in the taxane chemotherapy and Lu-PSMA-exposed patient population, where there is an increasing unmet patient need. The data were presented today in an oral symposium at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

"Patients whose disease progresses after Lu-PSMA therapy represent a growing population in prostate cancer, with no clearly defined standard of care for what comes next," said Philip Kantoff, MD, co-founder and CEO of Convergent Therapeutics. "These CONVERGE-01 data begin to establish meaningful benchmarks in the Lu-PSMA-exposed setting, including antitumor activity, emerging durability, manageable safety, and a convenient two-dose regimen in a population where burden of prior treatments is already high. These data also support our central thesis that in the alpha era, the mechanism of delivery is tantamount to the payload. By pairing Actinium-225 with a PSMA-directed antibody designed for enhanced tumor retention and limited normal tissue exposure, we believe CONV01-α has the potential to become an important next-generation therapy for mCRPC and across the disease continuum."

This interim dataset from Part 3 of CONVERGE-01 reflects 35 patients with progressive mCRPC previously treated with Lu-177-PSMA radioligand therapy, a clinically challenging population with heavy prior treatment exposure. All patients had received prior androgen receptor pathway inhibitor therapy, 80% had received prior taxane chemotherapy, and all had received Lu-PSMA therapy, including 23% with 1-3 cycles. The study provides prospective Phase 2 data to inform the company’s planned pivotal development strategy.

CONVERGE-01 Part 3 Study Highlights Include:

Median rPFS was 8.4 months in the target dose range in a Lu-PSMA-exposed patient population
Among 25 patients evaluable for PSA response, 40% experienced a PSA decline of ≥50% with similar declines across dose groups and among the patients resistant to Lu-PSMA
No dose-limiting toxicities were observed at any dose level
No treatment-related adverse events led to treatment discontinuation
Clinically manageable hematologic toxicity was observed without renal toxicity
Despite the fact that 48% of the patients entered the study with a history of xerostomia, no high-grade xerostomia was observed with CONV01-α treatment; 77% of patients had Grade 0 or 1 xerostomia following treatment with CONV01-α
"These data are encouraging as Converge-01 demonstrates meaningful anti-tumor activity and emerging durability in patients who have already received Lu-PSMA therapy. These data are striking given that the regimen is comprised of only two treatments, and a reduced treatment burden is important in this very advanced population," said Michael J. Morris, MD, Prostate Cancer Section Head, Memorial Sloan Kettering Cancer Center, and CONVERGE-01 study Scientific Advisory Committee Co-Chair. "The safety profile observed in CONVERGE-01 shows manageable hematologic toxicity, and no renal toxicity or high-grade xerostomia. These data support the continued evaluation of this PSMA-targeted alpha radioantibody approach in the Lu-PSMA-exposed setting."

Supply of Reliable, High-Purity Actinium-225

Convergent has reliable access to Ac-225, a necessary requirement to ensure late-stage clinical development, pivotal studies, and future commercial readiness. A flexible, networked CMC process allows for integration of multiple sources of Ac-225 from redundant suppliers. The Company has also secured Phase 3 supply via a recently expanded agreement with NorthStar Medical Radioisotopes for domestically-generated Ac-225 and co-located drug product manufacturing.

"A reliable Ac-225 supply chain is essential to advancing alpha radiotherapies from early stage development through commercial supply," said Caitlyn Harvey, Senior Vice President of Technical Operations at Convergent Therapeutics. "In CONVERGE-01, no patients missed a dose due to Actinium supply, underscoring the strength of our Ac-225 supply and manufacturing infrastructure. We are continuing to build the foundation needed to support CONV01-α through pivotal development and potential commercial production."

About the CONVERGE-01 Trial
The CONVERGE-01 trial is a Phase 2, randomized, open-label, multicenter four-part study designed to assess the safety and efficacy of CONV01-α in patients with mCRPC. In Part 1, patients received radiolabelled rosopatamab tetraxetan to characterize the biodistribution of the radioantibody to target organs and prostate cancer lesions. Participants were then enrolled in either Part 2 (dose optimization), Part 3 (dose escalation), or Part 4 (extended dosing regimen) depending on their prior treatment history. Part 2 enrolled, and Part 4 continues to enroll participants naïve to Lu-PSMA. Part 3 enrolled participants who were previously exposed to Lu-PSMA-radioligand therapy. Participants received CONV01-α in a two-dose regimen administered on Days 1 and 15. Further details of the trial can be found at www.clinicaltrials.gov under NCT identifier: NCT06549465.

About CONV01-α
CONV01-α is a PSMA-targeted Ac-225 radioantibody that pairs antibody precision with the localized potency of alpha radiation. CONV01-α, which is being developed to improve the treatment of mCRPC, uses a humanized monoclonal antibody (rosopatamab) directed against PSMA, a well-established and highly expressed antigen in prostate cancer. CONV01-α is differentiated by its ability to precisely deliver actinium-225 (Ac-225) through this PSMA-targeting antibody, enabling precise short-range, high-energy alpha particle radiation that creates focused DNA damage within tumor cells while limiting exposure to surrounding tissues. Initial studies in more than 120 patients have established clinical proof-of-concept for CONV01-α, showing consistent antitumor activity and a differentiated safety profile. This selectivity, combined with strong tumor retention and minimal salivary and renal uptake, supports the potential of CONV01-α to be a clinically impactful therapy for PSMA-positive cancers.

(Press release, Convergent Therapeutics, JUN 1, 2026, View Source;in-Lu-PSMA-Exposed-Metastatic-Castration-Resistant-Prostate-Cancer-mCRPC [SID1234666302])

On June 1, 2026 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery and development of drugs for the treatment of cancer, reported that efficacy results from a subset of patients treated with iopofosine I 131 immediately post-Bruton Tyrosine Kinase inhibitor (BTKi) therapy in the Company’s Phase 2 CLOVER WaM clinical trial of iopofosine I 131 to treat relapsed or refractory (r/r) Waldenström macroglobulinemia (WM) will be highlighted today in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper) taking place May 29-June 2, 2026 in Chicago, Illinois.

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"We are highly encouraged by these results from the CLOVER WaM study, which demonstrate compelling efficacy and durable responses with iopofosine I 131 in the particularly challenging patient population that has progressed following BTKi therapy. I look forward to highlighting these positive outcomes at this year’s ASCO (Free ASCO Whitepaper)," said Jarrod Longcor, chief operating officer of Cellectar Biosciences. "Patients with immediate post-BTKi disease represent a distinct clinical population within WM that is characterized by limited responses and rapid disease progression after BTKi discontinuation. In addition, there is no FDA-approved treatment that reliably provides durable disease control in this setting. These outcomes give us even greater confidence in the potential of iopofosine to be effective in an earlier line setting as will be evaluated in the planned Phase 3 confirmatory study."

In the CLOVER WaM Phase 2 clinical trial, eligible WM patients received greater than two prior therapies and had symptomatic disease requiring therapy. Treatment consisted of two cycles of iopofosine I 131 administered at 15 mCi/m2 on days 1 and 15 of each 57-day cycle. The primary efficacy endpoint was major response rate (MRR). This subset analysis assessed a modified intent-to-treat (mITT) population (all patients who received ≥60 mCi total administered dose of iopofosine I 131), and whose immediately prior treatment was a BTKi. Data cut off for this analysis was January 16, 2026.

Highlights of the Data:

Iopofosine I 131 demonstrated significant efficacy (n=24):
100% clinical benefit rate
87.5% overall response rate
79.2% major response rate, partial response or better
Median duration of response (DOR) of 16 months (range: 7.3 – 25.4 months)
20% of patients exceeded 30 months DOR
The treatment was well-tolerated with a manageable toxicity profile with cytopenias as the only Grade 3 or greater adverse event.
"These new data further reinforce the compelling clinical profile of iopofosine I 131, demonstrating meaningful efficacy in a subset of WM patients following BTKi treatment," said James Caruso, president and chief executive officer. "The strength and consistency of response observed in this post-BTKi population underscore iopofosine’s potential to address a critical unmet need in the second line setting and beyond. Based on these findings, we plan to pursue accelerated approval in the U.S. and initiate a confirmatory Phase 3 study in the fourth quarter of 2026. We remain committed to bringing iopofosine to the thousands of patients who may benefit from this therapy."

Details of the poster presentation are as follows:

Title: "Iopofosine I-131 after BTK inhibitors in Waldenström macroglobulinemia: CLOVER-WaM subgroup efficacy and safety"
Poster: 592
Date/Time: June 1, 2026, 9:00am – 12:00pm CDT
Presenter: Jarrod Longcor

(Press release, Cellectar Biosciences, JUN 1, 2026, https://www.cellectar.com/investors/news-events/press-releases/detail/393/cellectar-biosciences-to-highlight-compelling-new-efficacy-data-from-phase-2b-clover-wam-study-of-iopofosine-i-131-in-rr-waldenstrm-macroglobulinemia-at-the-american-society-of-clinical-oncology-annual-meeting [SID1234666301])

On June 1, 2026 Bristol Myers Squibb (NYSE: BMY) reported that the European Commission (EC) has approved Opdivo (nivolumab) in combination with doxorubicin, vinblastine and dacarbazine (AVD) for the treatment of adult and adolescent patients 12 years of age and older with previously untreated Stage III or IV classical Hodgkin Lymphoma (cHL). This approval marks a significant milestone, establishing the Opdivo plus AVD combination as the first immunotherapy-based regimen available in the European Union (EU) for newly diagnosed advanced cHL.1

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This new EC approval reinforces the expanding impact of Opdivo in cHL, building upon the U.S. Food and Drug Administration (FDA) approval of Opdivo in combination with AVD for previously untreated Stage III or IV cHL in adults and pediatric patients 12 years and older, granted in March 2026.2 Earlier this year, the EC also approved Opdivo in combination with brentuximab vedotin for the treatment of children 5 years of age and older, adolescents, and adults up to 30 years of age with relapsed or refractory cHL after one prior line of therapy.1

"Today’s approval of Opdivo in combination with AVD for previously untreated advanced classical Hodgkin Lymphoma marks an important advancement for patients in the European Union,1" said Monica Shaw, MD, senior vice president of Oncology Commercialization, Bristol Myers Squibb. "For decades, patients newly diagnosed with this aggressive blood cancer have faced intensive treatment approaches.3,4 This approval underscores the benefit and critical role of immunotherapy-based approaches in hematologic cancers like cHL and reflects our continued commitment to bringing these innovative options to patients earlier in their treatment journey across cancer types."

The EC approval is based on data from the Phase 3 SWOG 1826 (Study CA2098UT) which demonstrated a 58% reduction in the risk of disease progression or death with Opdivo in combination with AVD versus brentuximab vedotin plus AVD, as determined per investigator (Hazard Ratio [HR] 0.42; 95% Confidence Interval [CI] 0.27-0.67; P=<0.0001).The trial demonstrated a statistically significant improvement in the primary endpoint of progression-free survival (PFS), based on a median follow-up of 13.7 months in the intent to treat population. After a median follow-up of 36.7 months, the median overall survival (OS) had not been reached in either treatment arm with a total of 26 deaths: 9 (1.8%) deaths in the Opdivo in combination with AVD arm and 17 (3.4%) deaths in the standard of care over brentuximab vedotin plus AVD arm.5

"For patients with newly diagnosed Stage III or IV classical Hodgkin Lymphoma, finding an effective and tolerable first-line treatment remains crucial to achieving long-term remission, especially for adolescents and the elderly," said Franck Morschhauser, MD, PhD, Professor of Hematology at the University of Lille and Hospital Claude Huriez. "The SWOG 1826 study provided compelling data demonstrating that nivolumab-based combination therapy significantly improved progression-free survival compared with the standard of care. The availability of the first-ever IO combination in this earlier setting and across a broad spectrum of ages offers a potentially practice-changing approach to the treatment of frontline cHL."

This approval by the EC for Opdivo plus AVD for the treatment of adult and adolescent patients 12 years of age and older with previously untreated Stage III or IV cHL is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway. In addition to this approval in cHL, Opdivo-based options are also approved for treatment of multiple tumor types in the EU.

Bristol Myers Squibb thanks the SWOG Cancer Research Network and its investigators for leading the Phase 3 SWOG 1826 (CA2098UT) trial and the patients for their important contributions to this study.

About SWOG 1826 (CA2098UT)

SWOG 1826, also known as CA2098UT, is a randomized, multicenter, Phase 3 study evaluating Opdivo (nivolumab) in combination with doxorubicin, vinblastine and dacarbazine (AVD) for adult and pediatric (12 years and older) patients with previously untreated Stage III or IV classical Hodgkin Lymphoma (cHL).3 The study is designed to assess progression-free survival as the primary endpoint, with key secondary endpoints that include overall survival and other measures of efficacy and safety.3 The SWOG 1826 study is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) under a Cooperative Research and Development Agreement with Bristol Myers Squibb and conducted in the NCI National Clinical Trials Network (NCTN) led by the SWOG Cancer Research Network in collaboration with the Children’s Oncology Group (COG).3 It is the largest cHL study conducted in the NCTN.3 Bristol Myers Squibb co-sponsored the study and supplied Opdivo to the NCI through a Cooperative Research and Development Agreement.3

Select Safety Profile from SWOG 1826 (CA2098UT)

Serious adverse reactions occurred in 39% of patients receiving Opdivo in combination with doxorubicin, vinblastine and dacarbazine (AVD) (n=490). The most frequent serious adverse reactions reported in ≥5% patients who received Opdivo in combination with AVD were neutropenia (7%), pyrexia (7%), febrile neutropenia (6%), and nausea (6%). Fatal adverse reactions occurred in 3 patients (0.6%), all from sepsis. The most common adverse reactions were nausea (70%), neutropenia (61%), fatigue (59%), anemia (51%), constipation (49%), leukopenia (44%), musculoskeletal pain (42%), transaminases increase (41%), peripheral neuropathy (41%), vomiting (33%), and stomatitis (30%).

About Classical Hodgkin Lymphoma

Hodgkin lymphoma (HL), also known as Hodgkin disease, is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system.6 HL is the most common cancer diagnosed in adolescents (ages 15-19).7 It is most often diagnosed in early adulthood (ages 20-39) and late adulthood (older than 55 years of age).8 Classical Hodgkin lymphoma is the most common type of HL, accounting for 95% of cases.9 Despite progress in frontline therapy, advanced-stage HL still carries a substantial risk of relapse, highlighting the need for innovative approaches that deliver durable remission for patients.8

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients.

The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

INDICATIONS

OPDIVO (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.

OPDIVO is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.

OPDIVO (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).

OPDIVO (nivolumab) in combination with platinum-doublet chemotherapy, is indicated for neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by single-agent OPDIVO as adjuvant treatment after surgery.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

OPDIVO (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

OPDIVO (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

OPDIVO (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.

OPDIVO (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC).

OPDIVO (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC).

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.

OPDIVO (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

OPDIVO (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).

OPDIVO (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1).

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1).

OPDIVO (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma whose tumors express PD-L1 (≥1).

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 3.9% (26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%). In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune-mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to pneumonitis.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO, including Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%).

Immune-Mediated Hepatitis and Hepatotoxicity

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%).

OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. In patients receiving OPDIVO and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% of patients.

Immune-Mediated Endocrinopathies

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456) of patients, including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, adrenal insufficiency occurred in 7% (48/666) of patients, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%). In patients receiving OPDIVO and cabozantinib, adrenal insufficiency occurred in 4.7% (15/320) of patients, including Grade 3 (2.2%) and Grade 2 (1.9%).

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456) of patients, including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%).

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%).

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hyperthyroidism occurred in 12% (80/666) of patients, including Grade 3 (0.6%) and Grade 2 (4.5%).

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%).

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%), and Grade 2 (0.9%).

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated nephritis with renal dysfunction occurred in 4.1% (27/666) of patients, including Grade 4 (0.6%), Grade 3 (1.1%), and Grade 2 (2.2%).

Immune-Mediated Dermatologic Adverse Reactions

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.

YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated rash occurred in 16% (108/666) of patients, including Grade 3 (3.5%) and Grade 2 (4.2%).

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or OPDIVO in combination with YERVOY or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.

In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1% of patients unless otherwise specified: nervous system: autoimmune neuropathy (2%), myasthenic syndrome/myasthenia gravis, motor dysfunction; cardiovascular: angiopathy, temporal arteritis; ocular: blepharitis, episcleritis, orbital myositis, scleritis; gastrointestinal: pancreatitis (1.3%); other (hematologic/immune): conjunctivitis, cytopenias (2.5%), eosinophilia (2.1%), erythema multiforme, hypersensitivity vasculitis, neurosensory hypoacusis, psoriasis.

Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, which has been observed in patients receiving OPDIVO and YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 8% (4/49) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 5.1% (28/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 4.2% (5/119) of patients. In MPM patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, infusion-related reactions occurred in 12% (37/300) of patients.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO or YERVOY. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between OPDIVO or YERVOY and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO and YERVOY prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal studies, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and YERVOY and for at least 5 months after the last dose.

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

In randomized clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Lactation

There are no data on the presence of OPDIVO or YERVOY in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%), and pyrexia (10% and 1.0%). In Checkmate 238, serious adverse reactions occurred in 18% of patients receiving OPDIVO (n=452). Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. In Checkmate 816, serious adverse reactions occurred in 30% of patients (n=176) who were treated with OPDIVO in combination with platinum-doublet chemotherapy. Serious adverse reactions in >2% included pneumonia and vomiting. No fatal adverse reactions occurred in patients who received OPDIVO in combination with platinum-doublet chemotherapy. In Checkmate 77T, serious adverse reactions occurred in 21% of patients who received OPDIVO in combination with platinum-doublet chemotherapy as neoadjuvant treatment (n=228). The most frequent (≥2%) serious adverse reactions was pneumonia. Fatal adverse reactions occurred in 2.2% of patients, due to cerebrovascular accident, COVID-19 infection, hemoptysis, pneumonia, and pneumonitis (0.4% each). In the adjuvant phase of Checkmate 77T, 22% of patients experienced serious adverse reactions (n=142). The most frequent serious adverse reaction was pneumonitis/ILD (2.8%). One fatal adverse reaction due to COVID-19 occurred. In Checkmate 227, serious adverse reactions occurred in 58% of patients (n=576). The most frequent (≥2%) serious adverse reactions were pneumonia, diarrhea/colitis, pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency, and hypophysitis. Fatal adverse reactions occurred in 1.7% of patients; these included events of pneumonitis (4 patients), myocarditis, acute kidney injury, shock, hyperglycemia, multi-system organ failure, and renal failure. In Checkmate 9LA, serious adverse reactions occurred in 57% of patients (n=358). The most frequent (>2%) serious adverse reactions were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis, and respiratory failure. Fatal adverse reactions occurred in 7 (2%) patients, and included hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia. In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 057, fatal adverse reactions occurred; these included events of infection (7 patients, including one case of Pneumocystis jirovecii pneumonia), pulmonary embolism (4 patients), and limbic encephalitis (1 patient). In Checkmate 743, serious adverse reactions occurred in 54% of patients receiving OPDIVO plus YERVOY. The most frequent serious adverse reactions reported in ≥2% of patients were pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism. Fatal adverse reactions occurred in 4 (1.3%) patients and included pneumonitis, acute heart failure, sepsis, and encephalitis. In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY (n=547). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis. In Checkmate 9ER, serious adverse reactions occurred in 48% of patients receiving OPDIVO and cabozantinib (n=320). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection, and hyponatremia. Fatal intestinal perforations occurred in 3 (0.9%) patients. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 274, serious adverse reactions occurred in 30% of patients receiving OPDIVO (n=351). The most frequent serious adverse reaction reported in ≥2% of patients receiving OPDIVO was urinary tract infection. Fatal adverse reactions occurred in 1% of patients; these included events of pneumonitis (0.6%). In Checkmate 901, serious adverse reactions occurred in 48% of patients receiving OPDIVO in combination with chemotherapy. The most frequent serious adverse reactions reporting in ≥2% of patients who received OPDIVO with chemotherapy were urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3%), pulmonary embolism (2.6%), sepsis (2.3%), and platelet count decreased (2.3%). Fatal adverse reactions occurred in 3.6% of patients who received OPDIVO in combination with chemotherapy; these included sepsis (1%). OPDIVO and/or chemotherapy were discontinued in 30% of patients and were delayed in 67% of patients for an adverse reaction. In Checkmate 8HW, serious adverse reactions occurred in 46% of patients receiving OPDIVO in combination with ipilimumab. The most frequent serious adverse reactions reported in ≥1% of patients who received OPDIVO with ipilimumab were adrenal insufficiency (2.8%), hypophysitis (2.8%), diarrhea (2.0%), abdominal pain (2.0%), small intestinal obstruction (2.0%), pneumonia (1.7%), acute kidney injury (1.4%), immune mediated enterocolitis (1.4%), pneumonitis (1.4%), colitis (1.1%), large intestinal obstruction (1.1%), and urinary tract infection (1.1%). Fatal adverse reactions occurred in 2 (0.6%) patients who received OPDIVO in combination with ipilimumab; these included myocarditis and pneumonitis (1 each). In Checkmate 8HW, serious adverse reactions occurred in 39% of patients receiving OPDIVO alone. The most frequent serious adverse reactions reported in >1% of patients who received OPDIVO as a single agent were intestinal obstruction (2.3%), acute kidney injury (1.7%), COVID-19 (1.7%), abdominal pain (1.4%), diarrhea (1.4%), ileus (1.4%), subileus (1.4%), pulmonary embolism (1.4%), adrenal insufficiency (1.1%) and pneumonia (1.1%). Fatal adverse reactions occurring in 3 (0.9%) patients who received OPDIVO as a single agent; these included pneumonitis (n=2) and myasthenia gravis. In Checkmate 9DW, serious adverse reactions occurred in 53% of patients receiving OPDIVO with YERVOY (n=332). The most frequent non liver-related serious adverse reactions reported in ≥2% of patients who received OPDIVO with YERVOY were diarrhea/colitis (4.5%), gastrointestinal hemorrhage (3%), and rash (2.4%). Liver-related serious adverse reactions occurred in 17% of patients receiving OPDIVO with YERVOY, including Grade 3-4 events in 16% of patients. The most frequently reported all grade liver-related serious adverse reactions occurring in ≥1% of patients who received OPDIVO with YERVOY were immune-mediated hepatitis (3%), increased AST/ALT (3%), hepatic failure (2.4%), ascites (2.4%), and hepatotoxicity (1.2%). Fatal adverse reactions occurred in 12 (3.6%) patients who received OPDIVO with YERVOY; these included 4 (1.2%) patients who died due to immune-mediated or autoimmune hepatitis and 4 (1.2%) patients who died of hepatic failure. In Checkmate 040, serious adverse reactions occurred in 59% of patients receiving OPDIVO with YERVOY (n=49). Serious adverse reactions reported in ≥4% of patients were pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis. In Attraction-3, serious adverse reactions occurred in 38% of patients receiving OPDIVO (n=209). Serious adverse reactions reported in ≥2% of patients who received OPDIVO were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia. The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%). In Checkmate 577, serious adverse reactions occurred in 33% of patients receiving OPDIVO (n=532). A serious adverse reaction reported in ≥2% of patients who received OPDIVO was pneumonitis. A fatal reaction of myocardial infarction occurred in one patient who received OPDIVO. In Checkmate 648, serious adverse reactions occurred in 62% of patients receiving OPDIVO in combination with chemotherapy (n=310). The most frequent serious adverse reactions reported in ≥2% of patients who received OPDIVO with chemotherapy were pneumonia (11%), dysphagia (7%), esophageal stenosis (2.9%), acute kidney injury (2.9%), and pyrexia (2.3%). Fatal adverse reactions occurred in 5 (1.6%) patients who received OPDIVO in combination with chemotherapy; these included pneumonitis, pneumatosis intestinalis, pneumonia, and acute kidney injury. In Checkmate 648, serious adverse reactions occurred in 69% of patients receiving OPDIVO in combination with YERVOY (n=322). The most frequent serious adverse reactions reported in ≥2% who received OPDIVO in combination with YERVOY were pneumonia (10%), pyrexia (4.3%), pneumonitis (4.0%), aspiration pneumonia (3.7%), dysphagia (3.7%), hepatic function abnormal (2.8%), decreased appetite (2.8%), adrenal insufficiency (2.5%), and dehydration (2.5%). Fatal adverse reactions occurred in 5 (1.6%) patients who received OPDIVO in combination with YERVOY; these included pneumonitis, interstitial lung disease, pulmonary embolism, and acute respiratory distress syndrome. In Checkmate 649, serious adverse reactions occurred in 52% of patients treated with OPDIVO in combination with chemotherapy (n=782). The most frequent serious adverse reactions reported in ≥2% of patients treated with OPDIVO in combination with chemotherapy were vomiting (3.7%), pneumonia (3.6%), anemia (3.6%), pyrexia (2.8%), diarrhea (2.7%), febrile neutropenia (2.6%), and pneumonitis (2.4%). Fatal adverse reactions occurred in 16 (2.0%) patients who were treated with OPDIVO in combination with chemotherapy; these included pneumonitis (4 patients), febrile neutropenia (2 patients), stroke (2 patients), gastrointestinal toxicity, intestinal mucositis, septic shock, pneumonia, infection, gastrointestinal bleeding, mesenteric vessel thrombosis, and disseminated intravascular coagulation. In Checkmate 76K, serious adverse reactions occurred in 18% of patients receiving OPDIVO (n=524). Adverse reactions which resulted in permanent discontinuation of OPDIVO in >1% of patients included arthralgia (1.7%), rash (1.7%), and diarrhea (1.1%). A fatal adverse reaction occurred in 1 (0.2%) patient (heart failure and acute kidney injury). The most frequent Grade 3-4 lab abnormalities reported in ≥1% of OPDIVO-treated patients were increased lipase (2.9%), increased AST (2.2%), increased ALT (2.1%), lymphopenia (1.1%), and decreased potassium (1.0%).

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%).

In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%). In Checkmate 816, the most common (>20%) adverse reactions in the OPDIVO plus chemotherapy arm (n=176) were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%). In Checkmate 77T, the most common adverse reactions (reported in ≥20%) in patients receiving OPDIVO in combination with chemotherapy (n= 228) were anemia (39.5%), constipation (32.0%), nausea (28.9%), fatigue (28.1%), alopecia (25.9%), and cough (21.9%). In Checkmate 227, the most common (≥20%) adverse reactions were fatigue (44%), rash (34%), decreased appetite (31%), musculoskeletal pain (27%), diarrhea/colitis (26%), dyspnea (26%), cough (23%), hepatitis (21%), nausea (21%), and pruritus (21%). In Checkmate 9LA, the most common (>20%) adverse reactions were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%), rash (30%), decreased appetite (28%), constipation (21%), and pruritus (21%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 743, the most common adverse reactions (≥20%) in patients receiving OPDIVO plus YERVOY were fatigue (43%), musculoskeletal pain (38%), rash (34%), diarrhea (32%), dyspnea (27%), nausea (24%), decreased appetite (24%), cough (23%), and pruritus (21%). In Checkmate 214, the most common adverse reactions (≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547) were fatigue (58%), rash (39%), diarrhea (38%), musculoskeletal pain (37%), pruritus (33%), nausea (30%), cough (28%), pyrexia (25%), arthralgia (23%), decreased appetite (21%), dyspnea (20%), and vomiting (20%). In Checkmate 9ER, the most common adverse reactions (≥20%) in patients receiving OPDIVO and cabozantinib (n=320) were diarrhea (64%), fatigue (51%), hepatotoxicity (44%), palmar-plantar erythrodysaesthesia syndrome (40%), stomatitis (37%), rash (36%), hypertension (36%), hypothyroidism (34%), musculoskeletal pain (33%), decreased appetite (28%), nausea (27%), dysgeusia (24%), abdominal pain (22%), cough (20%) and upper respiratory tract infection (20%). In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO (n=236) were cough (14%) and dyspnea (14%) at a higher incidence than investigator’s choice. In Checkmate 275, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 274, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=351) were rash (36%), fatigue (36%), diarrhea (30%), pruritus (30%), musculoskeletal pain (28%), and urinary tract infection (22%). In Checkmate 901, the most common adverse reactions (≥20%) were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy. In Checkmate 8HW, the most common adverse reactions reported in ≥20% of patients treated with OPDIVO in combination with ipilimumab were fatigue, diarrhea, pruritus, abdominal pain, musculoskeletal pain, and nausea. In Checkmate 8HW the most common adverse reaction reported in ≥20% of patients treated with OPDIVO as a single agent, were fatigue, diarrhea, abdominal pain, pruritus, and musculoskeletal pain. In Checkmate 9DW, the most common adverse reactions (≥20%) in patients receiving OPDIVO with YERVOY (n=332) were rash (36%), pruritus (34%), fatigue (33%), and diarrhea (25%). In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO with YERVOY (n=49), were rash (53%), pruritus (53%), musculoskeletal pain (41%), diarrhea (39%), cough (37%), decreased appetite (35%), fatigue (27%), pyrexia (27%), abdominal pain (22%), headache (22%), nausea (20%), dizziness (20%), hypothyroidism (20%), and weight decreased (20%). In Attraction-3, the most common adverse reactions (≥20%) in OPDIVO-treated patients (n=209) were rash (22%) and decreased appetite (21%). In Checkmate 577, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=532) were fatigue (34%), diarrhea (29%), nausea (23%), rash (21%), musculoskeletal pain (21%), and cough (20%). In Checkmate 648, the most common adverse reactions (≥20%) in patients treated with OPDIVO in combination with chemotherapy (n=310) were nausea, decreased appetite, fatigue, constipation, stomatitis, diarrhea, and vomiting. In Checkmate 648, the most common adverse reactions reported in ≥20% of patients treated with OPDIVO in combination with YERVOY (n=322) were rash, fatigue, pyrexia, nausea, diarrhea, and constipation. In Checkmate 649, the most common adverse reactions (≥20%) in patients treated with OPDIVO in combination with chemotherapy (n=782) were peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain. In Checkmate 76K, the most common adverse reactions (≥20%) reported with OPDIVO (n=524) were fatigue (36%), musculoskeletal pain (30%), rash (28%), diarrhea (23%) and pruritis (20%).

Surgery Related Adverse Reactions

In Checkmate 77T, 5.3% (n=12) of the OPDIVO-treated patients who received neoadjuvant treatment, did not receive surgery due to adverse reactions. The adverse reactions that led to cancellation of surgery in OPDIVO-treated patients were cerebrovascular accident, pneumonia, and colitis/diarrhea (2 patients each) and acute coronary syndrome, myocarditis, hemoptysis, pneumonitis, COVID-19, and myositis (1 patient each).

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY.

Clinical Trials and Patient Populations

Checkmate 9DW-hepatocellular carcinoma, in combination with YERVOY; Checkmate 227-previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY, after prior treatment with sorafenib. ; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238–adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K–adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; 8HW: Previously Checkmate 142–MSI-H or dMMR metastatic colorectal cancer in combination with YERVOY; 8HW: Previously Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648-previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma in combination with chemotherapy; Checkmate 648-previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066-previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 77T–Neoadjuvant treatment with platinum-doublet chemotherapy for non-small cell lung cancer followed by single-agent OPDIVO as adjuvant treatment after surgery; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma.

(Press release, Bristol-Myers Squibb, JUN 1, 2026, View Source [SID1234666300])

On June 1, 2026 Avenzo Therapeutics, Inc. ("Avenzo"), a clinical-stage biotechnology company developing next-generation oncology therapies, reported updated clinical data from the Phase 1 portion of its ongoing Phase 1/2 clinical study of AVZO-021, its potentially differentiated cyclin-dependent kinase 2 (CDK2) selective inhibitor. The updated data demonstrated clinical activity in heavily pretreated patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Across all monotherapy doses, median progression-free survival (PFS) for all HR+/HER2- breast cancer patients, with a median of 4.0 (min, max: 1, 9) prior lines of therapies in the metastatic setting, was 5.3 months. Consistent with previously reported findings, AVZO-021 was generally well tolerated with relatively low incidence and severity of gastrointestinal and hematologic adverse events, which are commonly observed adverse events associated with less selective CDK inhibitors.

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The findings were reported at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

"HR+/HER2- breast cancer progression following CDK4/6 inhibitors represents a significant area of unmet need, with limited treatment options," said Manish R. Patel, M.D., Director of Drug Development, Florida Cancer Specialists/Sarah Cannon Research Institute. "CDK2 is increasingly recognized as a key driver of resistance in this setting. The updated data presented today for AVZO-021 continue to demonstrate encouraging clinical activity and favorable tolerability, further supporting its potential in combination treatment strategies, including with AVZO-023, Avenzo’s potentially differentiated CDK4 inhibitor."

AVZO-021, Phase 1 Updated Clinical Data

Utilizing a March 30, 2026 data cut-off date, 51 patients with advanced solid tumors were treated with AVZO-021 monotherapy, and 13 patients with HR+/HER2- breast cancer were treated with AVZO-021 in combination with fulvestrant.

Among all 51 patients, the median number of prior therapies in the metastatic setting was 3.0 (min, max: 0, 11), with all 33 patients with HR+/HER2- breast cancer having received at least one prior CDK4/6 inhibitor and 8 (24.2%) having received at least two prior CDK4/6 inhibitors in the metastatic setting.

Utilizing a May 7, 2026 data cut-off date for efficacy, 39 patients were efficacy-evaluable including 26 patients with HR+/HER2- breast cancer or CCNE1-amplified solid tumors treated with AVZO-021 monotherapy doses of 150 mg once daily (QD) and above with at least one evaluable post-baseline scan, and 13 patients with HR+/HER2- breast cancer treated with AVZO-021 in combination with fulvestrant with at least one evaluable post-baseline scan.

Updated Safety Results

A total of 64 patients comprise the safety population, including 51 patients with advanced solid tumors treated with AVZO-021 monotherapy at dose levels from 20 mg QD to 250 mg QD, and 13 patients with HR+/HER2- breast cancer treated with AVZO-021 in combination with fulvestrant at AVZO-021 dose levels of 150 mg QD and 200 mg QD.
All-grade treatment emergent adverse events (TEAEs) reported in greater than 20 percent of patients were nausea (52%), fatigue (48%), anemia (39%), and vomiting (34%).
The majority of TEAEs were Grade 1 or Grade 2.
Updated Pharmacokinetic and Pharmacodynamic Results

PK data suggested continuous CDK2 target coverage was achieved at doses of 90 mg QD and above.
Comparable exposures of AVZO-021 were observed between AVZO-021 monotherapy and in combination with fulvestrant at 150 mg QD and 200 mg QD, indicating no drug-drug interaction.
No food effects were observed in the pilot food effect substudy.
Decreases in circulating tumor DNA (ctDNA) were observed.
Updated Efficacy Results

Across all monotherapy doses, median PFS for all HR+/HER2- breast cancer patients (n=33), with a median of 4.0 (min, max: 1, 9) prior therapies, was 5.3 months (95% CI: 1.9, 7.2) with median follow-up time of 8.4 months.
The disease control rate for HR+/HER2- breast cancer efficacy-evaluable patients treated with 150 mg QD and above monotherapy (n=20) was 85% (95% CI: 62.1, 96.8).
Of 26 efficacy-evaluable patients treated with AVZO-021 monotherapy, four patients had a response (three with confirmed responses, and one with an unconfirmed response who remained on treatment awaiting a confirmatory scan) at the time of the data cut-off.
Of 13 efficacy-evaluable patients with HR+/HER2- breast cancer treated with AVZO-021 in combination with fulvestrant, two patients had confirmed responses.
All responders remained on treatment, including three patients on treatment for greater than 48 weeks.
"We are encouraged by the updated clinical data for AVZO-021, which continue to show clinical activity along with tolerability that we believe support combination strategies in HR+/HER2- breast cancer," said Mohammad Hirmand, M.D., Co-founder and Chief Medical Officer of Avenzo Therapeutics. "As we strive towards our goal of delivering novel and meaningful treatment options to patients, we are excited to be evaluating the combination of AVZO-021 and AVZO-023, our potentially differentiated CDK4 selective inhibitor, with fulvestrant in patients with HR+/HER2- breast cancer in the ongoing Phase 1 portion of the ORION-1 Phase 1/2 clinical study."

(Press release, Avenzo Therapeutics, JUN 1, 2026, View Source [SID1234666299])