On October 17, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Libtayo (cemiplimab) as an adjuvant treatment for adult patients with cutaneous squamous cell carcinoma (CSCC) at high risk of recurrence after surgery and radiation. The European Commission is expected to make a final decision on the application in the coming months. Libtayo was approved by the U.S. Food and Drug Administration (FDA) for these patients in the U.S. earlier this month.

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The positive opinion is supported by results from the global Phase 3 C-POST trial investigating adjuvant Libtayo versus placebo in patients with CSCC at high risk of recurrence following surgery and radiation. In the trial, Libtayo reduced the risk of disease recurrence or death by 68% compared to placebo (hazard ratio [HR]: 0.32; 95% confidence interval [CI]: 0.20-0.51; p<0.0001). Fewer patients treated with Libtayo had locoregional or distant recurrence compared with those who received placebo (4% vs. 17% and 5% vs. 13%, respectively). Detailed data were published in the New England Journal of Medicine (NEJM) in May 2025.

The safety profile of Libtayo as adjuvant treatment of patients with CSCC at high risk of recurrence after surgery and radiation is consistent with the known safety profile for Libtayo monotherapy in advanced cancers. In the trial, adverse events (AEs) occurred in 91% of patients receiving Libtayo (n=205) and 89% of patients receiving placebo (n=204). Grade ≥3 AEs occurred in 24% and 14% of patients in the Libtayo arm and the placebo arm, respectively. The most common AEs occurring in at least 10% of patients who received Libtayo were fatigue, pruritus, rash, diarrhea, arthralgia, hypothyroidism and maculo-papular rash. The only grade ≥3 AE that occurred in more than 2% of patients in the Libtayo arm was hypertension. AEs led to permanent discontinuation of treatment in 10% of patients who received Libtayo and 2% of patients who received placebo. Two patients in each arm experienced an AE leading to death.

About the Phase 3 Trial
C-POST was a randomized, placebo-controlled, double-blind, multicenter, global Phase 3 trial investigating Libtayo versus placebo as adjuvant treatment for patients with features associated with a high risk of CSCC recurrence and who had completed surgery and post-operative radiation therapy. Trial participants were at high risk of recurrence due to nodal features (extracapsular extension or ≥3 involved lymph nodes) and/or non-nodal features (in-transit metastases, T4 lesion, perineural invasion, or locally recurrent tumor with ≥1 additional poor prognostic features).

The trial enrolled 415 patients who were randomized to receive either Libtayo (n=209) or placebo (n=206) for up to 48 weeks. For the first 12 weeks, Libtayo 350 mg or placebo was administered intravenously every three weeks, followed by Libtayo 700 mg or placebo administered intravenously every six weeks for 36 weeks.

About CSCC
Cutaneous squamous cell carcinoma (CSCC) is a type of non-melanoma skin cancer (NMSC), and one of the most common cancers in the world. In the EU, the incidence of NMSC overall is expected to increase by 40% by 2040. CSCC can often be treated successfully with surgery, but many patients may have a "high risk" form that is more aggressive, and they face an increased risk of recurrence and disease progression.

(Press release, Regeneron, OCT 17, 2025, View Source [SID1234656777])

On October 17, 2025 Merck, a leading science and technology company, reported the presentation of longer-term results from the global Phase 3 MANEUVER trial evaluating pimicotinib, an investigational colony stimulating factor-1 receptor (CSF-1R) inhibitor in development by Abbisko Therapeutics Co., Ltd., for the treatment of patients with tenosynovial giant cell tumor (TGCT). This latest analysis showed that, with a median follow-up of 14.3 months, the objective response rate (ORR) for people treated with pimicotinib from the beginning of the study increased considerably to 76.2% (95% CI: 63.8, 86.0) by blinded independent review committee (BICR) per RECIST v1.1, from 54% at Week 25. The study also showed continued clinically meaningful improvements in key secondary endpoints related to patient outcomes such as pain and function. The safety profile was consistent with previously reported data. The results are being presented today in the Sarcoma mini-oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 (Presentation # 2690MO).

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"With the initial results of the global MANEUVER study presented earlier this year at ASCO (Free ASCO Whitepaper), pimicotinib demonstrated the highest objective response rate seen in a Phase 3 clinical trial of a systemic therapy in TGCT," said Prof. Niu Xiaohui, Director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital. "These latest findings build on those impressive results, showing that these tumor responses not only persist but deepen over time. Importantly, we also see continued improvements beyond one year in the patient-reported symptoms and functional outcomes that truly make a difference in patients’ abilities to go about their daily lives. Together, these findings indicate the potential for pimicotinib to be a best-in-class systemic treatment for patients with TGCT."

"TGCT causes pain, stiffness, and loss of range of motion, affecting patients’ ability to participate in activities of daily living and with their families or communities. Ultimately, this affects everyone and takes a mental and physical toll," said Sydney Stern, PhD, MS, TGCT Support, a Program of the Life Raft Group. "Patients benefit from more options that address their symptoms and shrink the disease. Importantly, addressing their symptoms enables patients to be the parents, partners, carers, and people they want to be without wondering when their TGCT will take over their life again."

The latest analysis of the global Phase 3 MANEUVER trial includes results from 63 patients who received pimicotinib for 24 weeks in Part 1 and then continued on pimicotinib in the open-label phase of the trial. With a median follow-up of 14.3 months, tumor responses continued to improve:

ORR per BIRC based on RECIST v1.1 increased to 76.2% (95% CI: 63.8, 86.0), from 54% at Week 25.
ORR per BIRC based on tumor volume score (TVS), an endpoint designed specifically for TGCT, increased to 74.6% (95% CI: 62.1, 84.7), from 61.9% at Week 25.
At the time of the data cutoff, the median duration of response was not reached (range: 0.03-19.81 months), with 93.7% of pimicotinib-treated patients experiencing a reduction in tumor size by BIRC per RECIST v1.1 at longer-term follow up.
Pimicotinib also demonstrated clinically meaningful improvements with longer-term follow-up up to week 73 in key patient-reported measures including range of motion, pain, stiffness and physical function that significantly impact people living with TGCT:

For relative range of motion, pimicotinib showed a mean change from baseline of 23.9% (increased from 15.6% at week 25).
Mean change from baseline continued to show improvements in physical function as measured by the patient-reported PROMIS-PF scale, and reductions in stiffness and pain as measured by the Worst Stiffness Numeric Scale Rating and Brief Pain Inventory worst pain rating, respectively.
The analysis also includes results for patients who were initially randomized to receive placebo in Part 1, then switched to pimicotinib in the open label part of the study (n=31). These patients experienced a clear benefit from pimicotinib treatment, with an ORR of 64.5% both by BICR per RECIST v1.1 and by TVS with a median follow-up of 8.5 months after switching to pimicotinib.

At longer-term follow-up, in patients who had received pimicotinib throughout the study, there were no new safety signals, and no evidence of cholestatic hepatotoxicity, drug-induced liver injury or hair/skin hypopigmentation. Most treatment-emergent adverse events remained mild in severity and were manageable.

"These longer-term results highlight the potential of pimicotinib to transform care by providing a systemic therapy that delivers meaningful, lasting benefit not only in terms of reducing tumor burden but in helping patients regain function and live with reduced pain," said Victoria Zazulina, M.D., Head of Development Unit, Oncology, Healthcare business of Merck. "Guided by this robust global study—conducted across North America, Europe and China—we are working with regulatory authorities as we seek to make this treatment available to patients as quickly as possible."

An application for marketing authorization of pimicotinib as a Class 1 innovative drug for adult patients with TGCT has been accepted for review by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA). Additional applications are planned in the U.S. and other markets around the world.

About MANEUVER

The pivotal global Phase 3 MANEUVER study is a three-part, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pimicotinib in patients with TGCT who require systemic therapy and have not received prior anti-CSF-1/CSF-1R therapy. The study is being conducted by Abbisko Therapeutics in China (n=45), Europe (n=28), and the U.S. and Canada (n=21).

In the double-blind Part 1, 94 patients were randomized 2:1 to receive either 50 mg QD of pimicotinib (n=63) or placebo (n=31) for 24 weeks. The primary endpoint was objective response rate (ORR) at week 25, as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review (BICR) in the intent-to-treat (ITT) population. Secondary endpoints include tumor volume score (TVS), relative range of motion, stiffness by Numeric Rating Scale (NRS), pain by Brief Pain Inventory (BPI), and physical function measured by Patient-Reported Outcomes Measurement Information System (PROMIS-PF).

After the double-blind Part 1, eligible patients could continue to the open-label Part 2 for up to 24 weeks of further treatment. Patients who completed Part 2 could then enter the open-label extension phase (Part 3) for extended treatment and safety follow-up.

About Pimicotinib (ABSK021)

Pimicotinib (ABSK021), which is being developed by Abbisko Therapeutics, is a novel, orally administered, highly selective and potent small-molecule inhibitor of CSF-1R. Pimicotinib has been granted breakthrough therapy designation (BTD) for the treatment of inoperable TGCT by China National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA), and priority medicine (PRIME) designation from the European Medicines Agency (EMA). Merck holds worldwide commercialization rights for pimicotinib.

Advancing the Future of Cancer Care

At Merck, we strive every day to improve the futures of people living with cancer. Building on our 350-year global heritage as pharma pioneers, we are focusing our most promising science to target cancer’s deepest vulnerabilities, pursuing differentiated molecules to strike cancer at its core. By developing new therapies that can help advance cancer care, we are determined to create a world where more cancer patients will become cancer survivors. Learn more at www.merckgroup.com.

(Press release, Merck & Co, OCT 17, 2025, View Source [SID1234656763])

On October 17, 2025 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported the expansion of its Phase III clinical development program of the novel, potential first-in-class investigational bispecific antibody, ivonescimab, into colorectal cancer (CRC) with the initiation of the global Phase III HARMONi-GI3 trial.

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Summit is starting a Phase III clinical study, HARMONi-GI3, to evaluate ivonescimab plus chemotherapy compared to bevacizumab plus chemotherapy as first line therapy in patients with unresectable metastatic colorectal cancer (CRC).

Clinical trial sites for HARMONi-GI3 are planned to begin activating in the United States prior to the end of the year. The multiregional study intends to enroll approximately 600 patients. The primary endpoint for this study is progression-free survival.

Each year, approximately 48,000 patients are estimated to be diagnosed with or have unresectable recurrent metastatic MSS CRC (also known as mismatch repair-proficient colorectal cancer, or pMMR CRC).1 There have been limited options approved in the United States in the last 20 years for those first-line patients whose tumors are not positive for certain biomarkers or other activating mutations.

MSS CRC is a setting where monoclonal PD-1 inhibitors such as pembrolizumab and nivolumab have failed to show a clinically meaningful benefit. Anti-VEGF therapy (e.g., bevacizumab) plus chemotherapy is the standard of care for many patients with 1L metastatic MSS CRC.

At the 2024 Annual Congress of the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) (ESMO 2024), Akeso Inc. (Akeso) presented encouraging Phase II data of ivonescimab in combination with FOLFOXIRI chemotherapy demonstrating an objective response rate (ORR) of 81.8% (95% CI: 59.7% – 94.8%) and a disease control rate (DCR) of 100% (95% CI: 84.6% – 100.0%) in 22 patients. This Phase II study, AK112-206, was conducted in China and sponsored by Akeso with all relevant data exclusively generated, managed, and analyzed by Akeso. In the ivonescimab plus FOLFOXIRI chemotherapy arm, there were no treatment emergent adverse events that led to permanent discontinuation of ivonescimab as of the data cutoff from the ESMO (Free ESMO Whitepaper) 2024 presentation.

Subsequently, AK112-206 was expanded to include additional patients from the United States and China to study ivonescimab in combination with FOLFOX chemotherapy. FOLFOX in combination with a monoclonal antibody such as bevacizumab represents a preferred treatment regimen for physicians treating patients in the United States and other western territories. The data from the initial patient cohort presented at ESMO (Free ESMO Whitepaper) 2024 have continued to mature, in addition to the global Phase II data generated in combination with FOLFOX in the United States and China, which support the Phase III HARMONi-GI3 study design using FOLFOX.

"As promised earlier in the year, we sought to expand the ivonescimab clinical development program beyond non-small cell lung cancer in order to continue to explore the potential benefits of its specifically-engineered, novel design and mechanism of action, including its cooperative binding attributes," stated Robert W. Duggan and Dr. Maky Zanganeh, Co-Chief Executive Officers of Summit. "Microsatellite stable colorectal cancer represents a global unmet need whereby ivonescimab has the potential to bring the benefits of immunotherapy to solid tumors where PD-1 monoclonal antibodies have not been able to successfully improve upon existing standards of care. We are thrilled by the potential of ivonescimab to make a significant difference to these patients with few front-line options available today."

Conference Call

Summit Therapeutics Inc. will host a conference call and live webcast to discuss recent updates related to ivonescimab, including data released at ESMO (Free ESMO Whitepaper), on Monday, October 20, 2025, at 8:00am ET. Conference call and webcast information will be accessible through our website www.smmttx.com.

An archived edition of the webcast will be available on our website later in the day on Monday.

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multi-fold higher affinity to PD-1 when in the presence of VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al., SITC (Free SITC Whitepaper), 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al., SITC (Free SITC Whitepaper), 2023) increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 3,000 patients have been treated with ivonescimab in clinical studies globally.

Summit began its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. In early 2025, the Company began enrolling patients in the United States for HARMONi-7. Summit intends to open clinical trial sites in the United States for the Phase III study in colorectal cancer (CRC) by the end of 2025.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a 3rd generation EGFR TKI (e.g., osimertinib). Enrollment in HARMONi was completed in the second half of 2024, top-line results were announced in May of 2025, with detailed results provided in September 2025.

HARMONi-3 is a Phase III clinical trial which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression.

HARMONi-7 is a Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.

HARMONi-GI3 is a planned Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with bevacizumab plus chemotherapy in patients with first-line unresectable metastatic CRC.

In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.

Akeso is actively conducting multiple Phase III clinical studies in settings outside of NSCLC, including biliary tract cancer, colorectal cancer, breast cancer, pancreatic cancer, small cell lung cancer, and head and neck cancer.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration (FDA) for the HARMONi clinical trial setting.

(Press release, Summit Therapeutics, OCT 17, 2025, View Source [SID1234656762])

On October 17, 2025 Astrazeneca reported positive results from the POTOMAC Phase III trial showed adding one year of treatment with AstraZeneca’s IMFINZI (durvalumab) to BCG induction and maintenance therapy demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) for patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC) compared to BCG treatment alone.

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The results of this final analysis will be presented today during a late-breaking Proffered Paper session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany (abstract #LBA108) and simultaneously published in The Lancet.

With a median follow-up of more than five years (60.7 months), the IMFINZI regimen showed a 32% reduction in the risk of high-risk disease recurrence or death versus the comparator arm (based on a DFS hazard ratio [HR] of 0.68; 95% confidence interval [CI] 0.50-0.93; P=0.0154). Estimated median DFS was not yet reached for either arm. An estimated 87% of patients treated with the IMFINZI regimen remained alive and disease-free at two years compared to 82% in the comparator arm.

The trial was not statistically powered to formally test overall survival (OS); however, after a median follow-up of more than five years (65.6 months, 14% maturity), a descriptive analysis showed an OS HR of 0.80 (95% CI 0.53-1.20), demonstrating that there was no detriment to OS.

Maria De Santis, MD, Head of the Interdisciplinary Uro-Oncology Section at Charité – Universitätsmedizin Berlin, Germany, and a principal investigator in the POTOMAC trial, said: "While patients with early-stage bladder cancer are treated with the goal of cure, early recurrence is common among those with high-risk non-muscle-invasive bladder cancer. This can lead to repeated surgical procedures and more intensive treatment, including removing a patient’s bladder which deeply affects their quality of life. The results of POTOMAC showed that adding one year of durvalumab to BCG bladder instillation treatment reduced the risk of recurrence by 32 per cent, allowing more patients to remain disease-free and alive at two years."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "The early and sustained disease-free survival benefit observed in the POTOMAC trial demonstrates IMFINZI has the potential to change the course of high-risk non-muscle-invasive bladder cancer by extending the time patients live without high-risk disease recurrence or progression. These results build on IMFINZI’s practice-changing impact in muscle-invasive bladder cancer and further validate our strategy to bring novel therapies into earlier-stage disease where they can have the greatest impact on patients’ lives."

Summary of results: POTOMAC

IMFINZI-based regimen

(n=339)

BCG induction and maintenance

(n=340)

DFS

Number of patients with event (%)

67 (20)

98 (29)

Median DFS (95% CI) (in months)i,ii,iii

NRiv
(NR-NR)

NR
(74.0-NR)

HR (95% CI)

0.68 (0.50-0.93)

Stratified log-rank p-valuev

0.0154

DFS rate at 12 months (%)

91.7

86.8

DFS rate at 24 months (%)

86.5

81.6

DFS rate at 36 months (%)

81.8

77.4

OSvi

Number of deaths (%)

41 (12)

52 (15)

HR (95% CI)

0.80 (0.53-1.20)

Median OS (95% CI) (in months)i

NR
(NR-NR)

NR
(NR-NR)

i. DFS cut-off date was April 3, 2025
i. Median follow-up duration for DFS at data cutoff: 60.7 months (interquartile range, 51.5-66.5)
ii. Calculated by Kaplan-Meier method
iii. Not reached
iv. For statistical significance, a 2-sided p-value of less than 0.0317, as determined by the Haybittle-Peto spending function, was required
v. Descriptive analysis, ITT; 14% maturity

The safety and tolerability of IMFINZI plus BCG induction and maintenance therapy was consistent with the known safety profiles of the individual medicines, with no new safety concerns identified. Grade 3 and 4 adverse events due to any cause occurred in 34% of patients treated with the IMFINZI regimen and 17% of patients in the comparator arm. The addition of IMFINZI did not compromise patients’ ability to complete BCG induction and maintenance therapy and had no major impact on patient-reported quality of life, supporting the benefit-risk profile of this combination.

IMFINZI is approved in the US, the European Union (EU), Japan and other countries for patients with muscle-invasive bladder cancer (MIBC) based on results from the NIAGARA Phase III trial, and continues to be investigated across early and late-stage bladder cancer in various treatment combinations, including in patients with MIBC who are ineligible or refuse to take cisplatin (VOLGA) and in locally advanced or metastatic disease (NILE).

IMPORTANT SAFETY INFORMATION

There are no contraindications for IMFINZI (durvalumab) or IMJUDO (tremelimumab-actl).

Severe and Fatal Immune-Mediated Adverse Reactions

Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs 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 before each dose. 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 IMFINZI and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and IMJUDO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg 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.

Immune-Mediated Pneumonitis

IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

IMFINZI as a Single Agent
In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions.
In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions.
The incidence of pneumonitis (including radiation pneumonitis) in patients with LS-SCLC following chemoradiation within 42 days prior to initiation of IMFINZI in ADRIATIC was 14% (37/262) in patients receiving IMFINZI and 6% (16/265) in patients receiving placebo. Of the patients who received IMFINZI (262), 0.4% had a fatal adverse reaction and 2.7% had Grade 3 adverse reactions.
The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy.
IMFINZI with IMJUDO
Immune‑mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions.
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions.
Immune-Mediated Colitis

IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal.

IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with 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.

IMFINZI as a Single Agent
Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.
IMFINZI with IMJUDO
Immune‑mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions. Intestinal perforation has been observed in other studies of IMFINZI and IMJUDO.
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Intestinal perforation and large intestine perforation were reported in 0.1% of patients.
Immune-Mediated Hepatitis

IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal.

IMFINZI as a Single Agent
Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions.
IMFINZI with IMJUDO
Immune‑mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4 (0.3%) and Grade 3 (4.1%) adverse reactions.
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2%) adverse reactions.
Immune-Mediated Endocrinopathies

Adrenal Insufficiency: IMFINZI and IMJUDO can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.
IMFINZI as a Single Agent
Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
IMFINZI with IMJUDO
Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions.
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.8%) adverse reactions.
Hypophysitis: IMFINZI and IMJUDO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated.
IMFINZI as a Single Agent
Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI.
IMFINZI with IMJUDO
Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO.
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions.
Thyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism): IMFINZI and IMJUDO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.
IMFINZI as a Single Agent
Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI.
Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
IMFINZI with IMJUDO
Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO.
Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions.
Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO.
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy.
Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions.
Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions.
IMFINZI with Carboplatin and Paclitaxel
Immune-mediated hypothyroidism occurred in 14% (34/235) of patients receiving IMFINZI in combination with carboplatin and paclitaxel.
Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated.
IMFINZI as a Single Agent
Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI.
IMFINZI with IMJUDO
Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up.
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including Grade 3 (0.3%) adverse reactions.
Immune-Mediated Nephritis with Renal Dysfunction

IMFINZI and IMJUDO can cause immune-mediated nephritis.

IMFINZI as a Single Agent
Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
IMFINZI with IMJUDO
Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse reactions.
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions.
Immune-Mediated Dermatology Reactions

IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.

IMFINZI as a Single Agent
Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.
IMFINZI with IMJUDO
Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions.
Immune-Mediated Pancreatitis

IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.

Other Immune-Mediated Adverse Reactions

The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI and IMJUDO or were reported with the use of other immune-checkpoint inhibitors.

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. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.
Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic.
Endocrine: Hypoparathyroidism.
Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.
Infusion-Related Reactions

IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses.

IMFINZI as a Single Agent
Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.
IMFINZI with IMJUDO
Infusion-related reactions occurred in 2.6% (10/388) of patients receiving IMFINZI and IMJUDO.
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions.
Complications of Allogeneic HSCT after IMFINZI

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. 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 PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO.

Lactation

There is no information regarding the presence of IMFINZI and IMJUDO in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3 months after the last dose.

Adverse Reactions

Unresectable Stage III NSCLC

In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (≥20%) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonia (7%) and pneumonitis/radiation pneumonitis (3.4%).
In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2%) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms.
Resectable NSCLC

In patients with resectable NSCLC in the AEGEAN study, the most common adverse reactions (occurring in ≥20% of patients) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash.
In patients with resectable NSCLC in the neoadjuvant phase of the AEGEAN study receiving IMFINZI in combination with platinum-containing chemotherapy (n=401), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6.7% of patients. Serious adverse reactions occurred in 21% of patients. The most frequent (≥1%) serious adverse reactions were pneumonia (2.7%), anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%), neutropenia (1%), and acute kidney injury (1%). Fatal adverse reactions occurred in 2% of patients, including death due to COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%), decreased appetite (0.2%), hemoptysis (0.2%), and death not otherwise specified (0.2%). Of the 401 IMFINZI treated patients who received neoadjuvant treatment and 398 placebo-treated patients who received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4), respectively, did not receive surgery due to adverse reactions.
In patients with resectable NSCLC in the adjuvant phase of the AEGEAN study receiving IMFINZI as a single agent (n=265), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 8% of patients. Serious adverse reactions occurred in 13% of patients. The most frequent serious adverse reactions reported in >1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and COVID-19 (1.1%). Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease and aortic aneurysm.
Metastatic NSCLC

In patients with mNSCLC in the POSEIDON study receiving IMFINZI and IMJUDO plus platinum-based chemotherapy (n=330), the most common adverse reactions (occurring in ≥20% of patients) were nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased appetite (28%), rash (27%), and diarrhea (22%).
In patients with mNSCLC in the POSEIDON study receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy (n=330), permanent discontinuation of IMFINZI or IMJUDO due to an adverse reaction occurred in 17% of patients. Serious adverse reactions occurred in 44% of patients, with the most frequent serious adverse reactions reported in at least 2% of patients being pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse reactions occurred in a total of 4.2% of patients.
Limited-stage Small Cell Lung Cancer

In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), the most common adverse reactions occurring in ≥20% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (38%), and fatigue (21%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonitis or radiation pneumonitis and pneumonia.
In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), IMFINZI was permanently discontinued due to adverse reactions in 16% of the patients receiving IMFINZI. Serious adverse reactions occurred in 30% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in ≥1% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (12%), and pneumonia (5%). Fatal adverse reactions occurred in 2.7% of patients who received IMFINZI including pneumonia (1.5%), cardiac failure, encephalopathy and pneumonitis (0.4% each).
Extensive-stage Small Cell Lung Cancer

In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%), and alopecia (31%). The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%).
In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy.
Locally Advanced or Metastatic Biliary Tract Cancers

In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse reactions (occurring in ≥20% of patients) were fatigue (42%), nausea (40%), constipation (32%), decreased appetite (26%), abdominal pain (24%), rash (23%), and pyrexia (20%).
In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to adverse reactions occurred in 6% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and acute kidney injury (2.4%). Fatal adverse reactions occurred in 3.6% of patients receiving IMFINZI plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients), and upper gastrointestinal hemorrhage (2 patients).
Unresectable Hepatocellular Carcinoma

In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), the most common adverse reactions (occurring in ≥20% of patients) were rash (32%), diarrhea (27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%), and abdominal pain (20%).
In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), serious adverse reactions occurred in 41% of patients. Serious adverse reactions in >1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8% of patients who received IMFINZI and IMJUDO, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). Permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients.
Primary advanced or Recurrent dMMR Endometrial Cancer

In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single-agent (n=44), the most common adverse reactions, including laboratory abnormalities (occurring in >20% of patients) were peripheral neuropathy (61%), musculoskeletal pain (59%), nausea (59%), alopecia (52%), fatigue (41%), abdominal pain (39%), constipation (39%), rash (39%), decreased magnesium (36%), increased ALT (32%), increased AST (30%), diarrhea (27%), vomiting (27%), cough (27%), decreased potassium (25%), dyspnea (25%), headache (23%), increased alkaline phosphatase (20%), and decreased appetite (18%). The most common Grade 3 or 4 adverse reactions (≥3%) were constipation (4.5%) and fatigue (4.5%).
In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single-agent (n=44), permanent discontinuation of IMFINZI due to adverse reactions occurred in 11% of patients. Serious adverse reactions occurred in 30% of patients who received IMFINZI with carboplatin and paclitaxel; the most common serious adverse reactions (≥4%) were constipation (4.5%) and rash (4.5%).
Muscle-Invasive Bladder Cancer (MIBC)

In patients with muscle-invasive bladder cancer (MIBC), the most common adverse reactions, including laboratory abnormalities, in the overall study (occurring in ≥20% of patients) were decreased hemoglobin, decreased neutrophils, increased blood creatinine, decreased sodium, nausea, increased ALT, decreased calcium, decreased platelets, fatigue, increased potassium, decreased lymphocytes, increased AST, constipation, decreased magnesium, decreased appetite, increased alkaline phosphate, rash, pyrexia, diarrhea, vomiting and abdominal pain.
In patients with MIBC in the neoadjuvant phase of the NIAGARA study receiving IMFINZI in combination with gemcitabine and cisplatin (n=530), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 9% of patients. Serious adverse reactions occurred in 24% of patients; the most frequent (≥1%) serious adverse reactions were pulmonary embolism (1.9%), febrile neutropenia (1.5%), acute kidney injury (1.3%), thrombocytopenia (1.3%), urinary tract infection (1.3%), and pneumonia (1.3%). Fatal adverse reactions occurred in 1.1% of patients including sepsis, myocardial infarction, and pulmonary embolism (0.2% each). One fatal adverse reaction of pneumonia was reported in 1 (0.2%) patient in the post-surgery phase before adjuvant treatment started. Of the 530 patients in the IMFINZI treatment arm and 526 patients in the chemotherapy treatment arm who received neoadjuvant treatment, 1 (0.2%) patient in each treatment arm did not receive surgery due to adverse reactions. The adverse reaction that led to cancellation of surgery in the IMFINZI treatment arm was interstitial lung disease.
In patients with MIBC in the adjuvant phase of the NIAGARA study receiving IMFINZI as a single agent (n=383), permanent discontinuation of adjuvant IMFINZI due to an adverse reaction occurred in 5% of patients. Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions (occurring in ≥1% of patients) were urinary tract infection (7%), acute kidney injury (3.7%), hydronephrosis (2.1%), pyelonephritis (2.1%), urosepsis (1.8%) and sepsis (1.6%). Fatal adverse reactions occurred in 1.8% of patients, including COVID-19, severe acute respiratory syndrome, cardiopulmonary failure, gastrointestinal hemorrhage, and chronic hepatic failure (0.3% each).
The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients.

Indications:

IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).

IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.

IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).

IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).

IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).

IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test.

IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle-invasive bladder cancer (MIBC).

Please see additional Important Safety Information throughout and Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO.

You may report side effects related to AstraZeneca products.

Notes

Bladder Cancer

Bladder cancer is the 9th most common cancer in the world, with more than 614,000 cases diagnosed each year.1 The most common type is urothelial carcinoma, which begins in the urothelial cells of the urinary tract.2

More than 70% of bladder cancer patients are diagnosed with NMIBC, an early-stage cancer where the tumor is in the tissue that lines the inner surface of the bladder but has not invaded the muscle wall.2-3 About half of patients with NMIBC are classified as high-risk for disease progression or recurrence because of certain characteristics of their cancer, such as tumor grade, stage and specific tumor features.4

In 2024, an estimated 125,000 patients were treated for high-risk NMIBC, for which the current standard of care is transurethral resection of bladder tumor (TURBT) followed by instillation of BCG directly into the bladder.5-6 Up to 80% of patients experience disease recurrence within five years, and rates of progression in high-risk patients can be as high as 30%.4,7 Many patients with recurrent disease undergo additional rounds of chemotherapy and repeated invasive procedures such as TURBT, as well as the potential need for cystectomy (surgery to remove the bladder), underscoring the critical need for new treatment options in this curative-intent setting.6

POTOMAC

POTOMAC is a randomized, open-label, multi-center, global Phase III trial evaluating IMFINZI in combination with BCG therapy as a treatment for 1,018 patients with BCG-naïve, high-risk NMIBC who have undergone TURBT prior to randomization. Patients were randomized 1:1:1 to receive IMFINZI plus BCG induction and maintenance therapy, or IMFINZI plus BCG induction-only therapy, versus BCG induction and maintenance therapy. In the POTOMAC trial, patients received six weeks of BCG induction therapy with or without two years of BCG maintenance therapy. With median follow-up for DFS exceeding five years, the POTOMAC trial features a notably long observation period among NMIBC trials.

The trial was conducted in more than 120 centers across 12 countries including Canada and others across Europe and Asia. The primary endpoint was DFS, defined as time from randomization to date of first recurrence of high-risk disease or death from any cause, for IMFINZI plus BCG induction and maintenance therapy compared to BCG induction and maintenance therapy alone. Secondary endpoints included DFS for IMFINZI plus BCG induction only therapy versus the comparator arm, as well as OS at five years and safety across both experimental arms of the trial.

IMFINZI

IMFINZI (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

In addition to its indication in MIBC, IMFINZI is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, IMFINZI is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of IMJUDO (tremelimumab-actl) and chemotherapy for the treatment of metastatic NSCLC. IMFINZI is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy for the treatment of extensive-stage SCLC.

IMFINZI is also approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with IMJUDO in unresectable hepatocellular carcinoma (HCC). IMFINZI is also approved as a monotherapy in unresectable HCC in Japan and the EU.

IMFINZI in combination with chemotherapy followed by IMFINZI monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in the US and EU). IMFINZI in combination with chemotherapy followed by olaparib and IMFINZI is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in the EU and Japan.

Since the first approval in May 2017, more than 414,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several gastrointestinal cancers.

(Press release, AstraZeneca, OCT 17, 2025, View Source [SID1234656761])

On October 17, 2025 CatalYm, a world-leader in neutralizing GDF-15 in cancer and cachexia, reported compelling primary results from the Phase 2 GDFATHER-NEO trial in an oral late-breaking session at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025. The data demonstrated that Growth Differentiation Factor-15 (GDF-15) blockade by visugromab enhanced the efficacy of PD-1 inhibition by nivolumab as a neoadjuvant therapy in muscle-invasive bladder cancer (MIBC), with a similar safety profile compared to nivolumab plus placebo. Visugromab is a humanized, monoclonal antibody designed to neutralize the tumor-derived cytokine GDF-15 which plays a central role in immune suppression and anti-PD-(L)1 treatment resistance.

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Prof. Dr. Andrea Necchi, Director of Genitourinary Medical Oncology at IRCCS San Raffaele Hospital and Principal Investigator of the trial, presented the late-breaking data, underscoring the potential of the visugromab combination as a new treatment option in this indication, where standard chemotherapy is hindered by limited activity and significant off-target toxicity.

"The impact seen in this checkpoint naive setting demonstrates the activity of visogromab with a PD-1 inhibitor in an earlier line of treatment and builds on the benefit seen in patients with refractory disease," said Sujata Rao, MD, Chief Medical Officer at CatalYm.

"MIBC still has a poor 5-year survival rate of around 50%. As many patients are diagnosed at an older age and/or with existing comorbidities, a significant number are not eligible for aggressive standard-of-care neoadjuvant chemotherapy, and a proportion refuse to undergo radical cystectomy after neoadjuvant therapy. Previous combinations of chemotherapy with anti-PD-(L)1 therapy have shown limited or non-additive clinical benefit with regards to the pathological response. There is a clear need for efficient new treatment regimens endowed with minimal side effects to improve patient outcomes," said Prof. Dr. Andrea Necchi, Director of Genitourinary Medical Oncology at IRCCS San Raffaele Hospital and Principal Investigator of the trial. "These early results for the novel visugromab/anti-PD-1 combination are promising, demonstrating enhanced anti-tumor activity. Moreover, its good safety and tolerability profile suggest that even more vulnerable or frail patients may potentially benefit from this new treatment approach."

The multicenter, single-blinded Phase 2 GDFather-NEO trial (NCT06059547) investigates visugromab plus nivolumab vs. nivolumab plus placebo, in cisplatin-ineligible/refusing patients with newly diagnosed MIBC that had not spread to the lymph nodes or distant organs. The combination was administered every four weeks for three cycles. Radical cystectomy or re-transurethral resection of the bladder tumor (re-TURBT) was performed 4-8 weeks after the last dose. Key endpoints of the trial are pathological complete response (pCR)1, major pathologic response (MPR)2 and radiologic objective response rate (rORR)3.

Key trial results

Out of 31 patients enrolled with a median age of 76 years, 29 were efficacy-evaluable (n=15 in the nivolumab + visugromab (N+V) arm, n=14 in the nivolumab + placebo (N+P) arm) at the data cut-off on September 29, 2025.
Efficacy analysis demonstrated substantially higher pCR (33.3% vs. 7.1%) and MPR (66.7% vs. 21.4%) in the N+V arm compared to the N+P arm.
The rORR (as per RECIST v1.1 criteria) was approximately four times higher in the N+V combination with 60.0% (7 complete responses, 2 partial responses), compared to 14.3% (0 complete responses, 2 partial responses) in the N+P arm.
The visugromab combination performed superior across all clinical tumor stages, and dominantly in PD-L1-positive patients (CPS≥10%)4.
More participants in the visugromab combination arm were eligible to receive the bladder-sparing re-TURBT surgery approach (n=6 in the N+V arm vs. n=3 in the N+P arm).
Based on early safety and tolerability assessment, the N+V combination demonstrated good tolerability, in line with the expected safety profile of nivolumab monotherapy.
Most Treatment-Related Adverse Events (TRAEs) were mild to moderate, with some Grade 3 clinical and laboratory events as expected in this population. No differences in type, severity or frequency of events were observed between the two trial arms.
Baseline serum GDF-15 levels and immune cell profile were comparable between the N+V and N+P arms.
"Our latest data update indicates that we are on the right path with our GDF-15 neutralizing approach as a powerful new regimen in cancer treatment," said Scott Clarke, Chief Executive Officer at CatalYm. "These results extend our clinical findings into earlier lines of therapy and demonstrate proof-of-concept for visugromab in another hard-to-treat tumor indication. We are committed to rapidly advancing our targeted Phase 2b program, an important next step on our mission to improve the outcomes for a broad range of cancer patients in need."

The Phase 2 GDFATHER-NEO trial is still ongoing with biomarker analysis of blood and tumor microenvironment focused on treatment-induced changes specific to visugromab therapy as well as a final safety assessment. CatalYm is conducting a broad Phase 2b clinical program with randomized trials in 1L and 2L non-small cell lung cancer, 2L hepatocellular carcinoma and cachexia underway.

About Visugromab

Visugromab is a monoclonal antibody that neutralizes Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant produced by tumors which fosters resistance to therapy and drives cachexia in people with cancer. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms and induces an efficient anti-tumor response by enabling immune cell activation, proliferation and induction of interferon-γ. In addition, visugromab also mitigates cancer cachexia, a severe condition affecting a significant number of advanced cancer patients by inhibiting the activation of the GFRAL pathway in the brainstem, a key driver of weight loss and appetite suppression in cancer patients.

(Press release, Catalym, OCT 17, 2025, View Source [SID1234656760])