On May 21, 2026 Merck, a leading science and technology company, reported that the first patient has been dosed in the Phase 3 PROCEADE-CRC-03 trial (NCT07549412). The study is evaluating precemtabart tocentecan (Precem‑TcT), a potential first‑in‑class investigational anti‑CEACAM5 antibody‑drug conjugate (ADC), for the treatment of metastatic colorectal cancer (mCRC).

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"Leveraging our novel payload‑linker technology, Precem‑TcT is the first CEACAM5‑targeted ADC in clinical studies with an exatecan payload, rationally designed for stability and enhanced cancer cell killing activity," said David Weinreich, MD, MBA, Global Head of R&D and Chief Medical Officer for the Healthcare business of Merck. "The Phase 3 study and the enrollment of the first patient with Precem-TcT build on the Company’s more than 20 years of expertise in colorectal cancer, and highlight our commitment to advancing differentiated ADCs for heavily pretreated patients with limited treatment options."

The PROCEADE-CRC-03 study assesses the efficacy and safety of Precem-TcT, alone or with bevacizumab, in patients with mCRC who are intolerant- or refractory-to, or progressed after, systemic therapies. The PROCEADE-CRC-03 study will be conducted in approximately 165 sites in 20 countries and will recruit approximately 1,020 patients with mCRC.

In Phase 1 (PROCEADE-CRC-01; NCT05464030), Precem-TcT as monotherapy or in combination showed predictable and manageable safety in more than 100 patients with heavily pretreated mCRC. At the recommended dose for Phase 3 development (2.8 mg/kg Q3W; n=29), confirmed objective response rate (cORR) was 20.7% (95% CI: 8.0, 39.7), median PFS was 6.9 months (95% CI: 4.4, 9.5) and median OS was not reached (95% CI: 8.7, NE) after a median follow-up of 13.1 months.

"The PROCEADE-CRC-03 Phase 3 study is designed to address significant unmet needs for patients with metastatic colon cancer whose disease has progressed after standard therapies," said Kanwal P.S. Raghav, MBSS, MD, Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston. "The data from the phase 1 study suggested a manageable safety profile for Precem-TcT and encouraging early tumor response in the patients with heavily pre-treated metastatic colorectal cancer. CEACAM5 is largely absent from healthy tissues and is overexpressed in nearly all mCRC cases, supporting a non-selective, universal patient approach, and represents a promising therapeutic target in this setting."

Globally, CRC is the third-most commonly diagnosed malignancy and the second leading cause of cancer-related deaths.1 Merck chose mCRC as the first indication to assess the efficacy and safety of Precem-TcT because ~90% of colorectal cancers overexpress CEACAM5,2 and there is a high unmet clinical need in patients with metastatic colorectal cancer, especially among those who progressed on several previous therapies.3,4,5 Patients with advanced colorectal cancer typically face a challenging prognosis, with few options available for those whose disease continues to progress after three or more lines of therapy. Additionally, with progression, response to treatment and prognosis become increasingly worse over time.

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.

About Precemtabart tocentecan (M9140)

Precemtabart tocentecan is an investigational anti-CEACAM5 antibody-drug conjugate (ADC). Leveraging the company’s novel linker-payload technology, precemtabart tocentecan is the first CEACAM5 ADC with an exatecan payload, a potent topoisomerase inhibitor (TOP1i), which has been rationally designed for stability in circulation and superior cancer cell killing activity. Beyond the direct effect on the target cell, precemtabart tocentecan has been shown in preclinical research to induce tumor cell death through a bystander effect in which exatecan permeates the cell membrane to neighboring cells, inducing apoptosis (cell death). This bystander effect within the tumor microenvironment may enhance efficacy. Precemtabart tocentecan is currently being evaluated across tumor types with CEACAM5 expression and a high unmet need, including metastatic colorectal cancer (mCRC), gastric cancer (GC), non-small cell lung cancer (NSCLC), and pancreatic ductal adenocarcinoma (PDAC).

About Colorectal Cancer

Colorectal cancer (CRC) is cancer of the colon or rectum, which often arises from benign polyps that eventually turn cancerous. It is the third most common diagnosed malignancy, and the second leading cause of cancer deaths worldwide with approximately 1 in 10 cancer deaths attributed to CRC. Despite new therapies, 5-year survival of stage 4 CRC is <20%. The global burden of CRC has substantially increased over time and is expected to increase by 60% to more than 2.2 million new cases and 1.1 million deaths by 2030.

(Press release, Merck & Co, MAY 21, 2026, View Source [SID1234665977])

On May 21, 2026 Foundation Medicine, Inc., a global, patient-focused precision medicine company, reported that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOneCDx to be used as a companion diagnostic (CDx) for TEPMETKO (tepotinib) developed by EMD Serono, the healthcare business of Merck KGaA, Darmstadt, Germany in the U.S. and Canada. TEPMETKO received accelerated approval from the FDA in February 2021 and traditional approval in February 2024 for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations (METex14).1

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METex14 is found in 3-4% of NSCLC cases2 and is commonly associated with advanced disease and a poor prognosis.3 In November 2024, through Foundation Medicine’s longstanding partnership with Merck KGaA, Darmstadt, Germany, Foundation Medicine’s high-quality blood-based comprehensive genomic profiling test, FoundationOneLiquid CDx, became the first FDA-approved companion diagnostic to identify patients who may be eligible for TEPMETKO.

FoundationOne CDx as a companion diagnostic for this therapy marks the company’s first approval leveraging its real-world data-powered CDx offering, a service that supports drug and diagnostic label expansion by supplementing clinical trials with expertly curated real-world evidence and integrated regulatory support. Drawing on data from over 150,000 patients in the Flatiron Health-Foundation Medicine Clinico-genomic Database (CGDB), Foundation Medicine is well-positioned to generate relevant and harmonized real-world data (RWD) cohorts reducing the need for incremental patient enrollment while maintaining the rigor required for regulatory use in companion diagnostic projects.

Foundation Medicine is the global leader in companion diagnostic indications.4 With today’s approval, it has more than 20 FDA-approved companion diagnostic indications for NSCLC, and over 100 approved companion diagnostic indications in total, the most of any comprehensive genomic profiling company.5

"This approval reinforces the importance of having diverse, high-quality testing options to support healthcare providers in making informed treatment decisions for their patients, regardless of available sample type," said Todd Druley, M.D., Ph.D., Chief Medical Officer at Foundation Medicine. "This milestone also highlights our commitment to finding novel avenues to enable expanded patient access. In the many cases where samples are depleted and the time needed for a new trial is unfeasible, rigorous, regulatory-aligned real-world evidence can complement pre-existing clinical trial data to help expand the available options for patients."

"Innovation in targeted therapies for lung cancer has helped pave the way for progress in precision medicine, but there is still so much work needed to connect the right patients to the right therapies, and to find new options for patients," said Danielle Hicks, Co-Interim Chief Executive Officer and Chief Patient Officer at GO2 for Lung Cancer. "We’re excited to see the value that regulatory-grade, real-world data can add to increase agility, while maintaining the highest standards for patient care."

Foundation Medicine is the only company to offer both tissue and blood-based comprehensive genomic profiling tests that are approved by the FDA. Using a tissue sample, the FDA-approved FoundationOne CDx test analyzes more than 300 cancer-related genes in a patient’s tumor.

(Press release, Foundation Medicine, MAY 21, 2026, View Source [SID1234665976])

On May 21, 2026 Obsidian Therapeutics, Inc., a clinical-stage biopharmaceutical company harnessing novel protein-regulation technology to develop engineered tumor-infiltrating lymphocyte (TIL) cell therapies, reported positive Phase 2 results in patients with advanced melanoma from the Phase 1/2 Agni-01 multicenter study of OBX-115. These data will be presented in an oral presentation by Allison S. Betof, M.D., Ph.D., FASCO, associate professor of medicine (oncology), Stanford School of Medicine, on Monday, June 1, 2026, at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

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OBX-115 is a novel engineered TIL cell therapy armored with pharmacologically regulatable membrane-bound IL15 and designed to deliver an improved, patient-centric treatment regimen. With its potentially reduced treatment burden driven by option for less-invasive core needle biopsy tumor tissue procurement, exclusively low-dose lymphodepletion (LD) compatible with outpatient administration and elimination of IL2 in the treatment regimen, OBX-115, if approved, has the potential to become a meaningful therapeutic option and expand the cell therapy eligible population of patients with advanced or metastatic melanoma.

Oral Presentation Title: OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients with advanced melanoma that has progressed on/after immune checkpoint inhibitors (ICI): Phase 2 results
Session Title: Oral Abstract Session – Melanoma/Skin Cancers
Abstract: #9507
Location: Grand Ballroom S100bc
Session Date and Time: June 1, 8:00AM-11:00AM CT
Presentation Time: 10:12 AM-10:24 AM CT

Data to be presented are from the single-arm open-label Phase 1/2 Agni-01 multicenter study (NCT06060613) assessing the safety and efficacy of OBX-115 in adult patients with advanced melanoma that has progressed following treatment with ICI. Results from the January 22, 2026 data cutoff include 15 patients treated at the recommended phase 2 dose (RP2D), with n=6 from Phase 1 and n=9 from Phase 2.

OBX-115 demonstrated strong efficacy with a 67% objective response rate (ORR) in a difficult-to-treat advanced melanoma patient population

Study conducted in high unmet need melanoma patients, including a majority (93%) who were previously treated with doublet ICI
73% of patients had progression after anti–PD-1 + anti–CTLA-4 doublet therapy, a group with particularly low response rates to subsequent therapy
67% ORR (per RECIST v1.1), including 2 confirmed complete responses (CR) and 8 confirmed partial responses (PR) (compared to 1 CR and 9 PRs in abstract text)
Durable clinical benefit, including 8 of 10 responses ongoing as of the median 4.3 month study follow-up
OBX-115 continues to deliver consistent, favorable safety profile; treatment regimen with low-dose lymphodepletion and no IL2

All patients received low-dose LD, including 4 in the outpatient setting
No dose-limiting toxicities (DLT), treatment-related mortality (TRM), immune effector cell-associated neurotoxicity syndrome (ICANS) or ICU transfers
Majority of treatment-emergent adverse effects (TEAEs) occurring in ≥20% of patients were Grade 2 or less
Dr. Betof commented, "These data highlight OBX-115’s promising safety and efficacy profile, demonstrating the potential for durable benefit with low rates of major safety signals, including no DLTs, ICU transfer or TRM. The notable reduction in patient treatment burden relative to other therapies, driven by attributes such as core needle biopsy tumor tissue procurement and treatment regimen with outpatient-compatible low-dose lymphodepletion and without IL2, could be very beneficial and broaden the number of cell therapy eligible patients."

"Results from the Agni-01 study, including the 67% ORR, with 80% of responses ongoing as of the median 4.3 month study follow up, further emphasize OBX-115’s potential in advanced melanoma. We are highly encouraged by the anticipated benefit demonstrated in patients with difficult-to-treat advanced melanoma, including patients with disease progression following anti–PD-1 combination exposure," said Parameswaran Hari, M.D., M.S., Chief Medical Officer of Obsidian. "We have been in discussions with the FDA, and after reaching alignment on key design elements including eligibility criteria, clinical trial endpoints and drug product potency assay, plan to pursue a single-arm accelerated approval pathway. We look forward to continuing to advance OBX-115 through the clinic and plan to begin treating patients in the registration-enabling cohort of our multicenter study in mid-2026."

Obsidian is also investigating OBX-115 in patients with non-small cell lung cancer (NSCLC) in the Agni-01 trial. NSCLC Phase 1 data are expected in the first half of 2027.

About OBX-115
Obsidian’s lead investigational cytoTIL15 program, OBX-115, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential, if approved, to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process designed to enhance persistence, antitumor activity, and clinical safety of TIL cell therapy. Obsidian is investigating OBX-115 in the phase 1/2 Agni-01 multicenter trial in patients with advanced solid tumors (NCT06060613).

(Press release, Obsidian Therapeutics, MAY 21, 2026, View Source [SID1234665975])

On May 21, 2026 A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage immunotherapy company developing first-in-class logic-gated therapies for solid tumors, reported the presentation of safety and efficacy data from the ongoing EVEREST-2 clinical study (NCT06051695). The findings, which are being presented in poster presentations during the 2026 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) taking place May 29 – June 2, 2026, in Chicago, include updates on the first reported complete response (CR) in a patient with non-small cell lung cancer (NSCLC) following treatment with A2B694, a logic-gated mesothelin (MSLN)-targeted TmodTM chimeric antigen receptor T-cell (CAR T-cell) therapy.

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Complete responses have rarely been observed in studies of CAR T-cell therapies for the treatment of solid tumors, and to date none has been reported in patients with lung cancer.1

"We are encouraged by the EVEREST-2 study data being presented during ASCO (Free ASCO Whitepaper) 2026, including updated results for the first reported complete response to CAR T-cell therapy in a patient with a hard-to-treat case of non-small cell lung cancer. These findings support the potential for logic-gated therapies, such as A2B694, to treat solid tumors. We eagerly await the results from A2B543, the armored version of A2B694, which has the potential for greater potency without compromising safety," said Salman R. Punekar, M.D., assistant professor of medicine, NYU Langone Health, Perlmutter Cancer Center and treating physician of the patient.

EVEREST-2 Study Arm 1: Efficacy and Safety Update for A2B694

As of January 5, 2026, 13 patients were enrolled in phase 1: eight women and five men, with a median age of 59 years; 11 were non-Hispanic White and two were Hispanic/unknown race. Tumor types included ovarian (n = 3), pancreatic (n = 3), NSCLC (n = 1), colorectal (n = 4), gastro-esophageal (n = 1), and mesothelioma (n = 1). A2B694 dose groups were 1×108 (n = 3), 2×108 (n = 4), 4×108 (n = 5), and 6×108 plus low-dose IL-2 (n = 1) cells.

Lymphodepletion prior to administration of A2B694 was well-tolerated by all patients, with expected transient cytopenias. All patients had at least one adverse event; all adverse event terms were reported in one patient each, except for grade 3 neutropenia, which was reported in two patients. One patient had grade 3 ICANS managed with corticosteroids and one patient had grade 1 CRS confounded by IL-2 administration. There were no dose-limiting toxicities or new safety signals after up to 17 months of follow-up. No deaths were attributed to A2B694, and no patient has discontinued the study due to adverse events.

One patient with co-mutated (KRAS G12V/STK11) NSCLC, a subtype associated with resistance to chemoimmunotherapy and poor prognosis, had progressed on standard-of-care first-line treatment of carboplatin, pemetrexed, and pembrolizumab before enrolling in EVEREST-2. At month 3 post-infusion of A2B694, the patient achieved a complete response (CR) per RECIST 1.1 and had a confirmed CR by central review at month 6 as well as a PET-CT scan which showed no evidence of disease. At month 8, the patient had an isolated CNS relapse, with an ongoing non-CNS CR per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) at month 9. At 15 months, the patient’s CT showed no new findings, and persistence of A2B694 in the blood was confirmed by ddPCR.

EVEREST-2 Study Arm 2: Enrollment Update on A2B543

An additional presentation from the EVEREST-2 study is a trials-in-progress poster about A2B543, a CAR T-cell therapy which uses the same logic-gated construct as A2B694, armored with the addition of a membrane-tethered IL-12 (mem-IL-12) booster.

IL-12 is a potent, pro-inflammatory cytokine that plays a crucial role in inducing antitumor immune responses; however, systemic IL-12 can be prohibitively toxic. In A2B543, expression of the mem-IL-12 cassette is under the control of an NFAT promoter and is induced during antigen engagement or T cell activation. This inducible mem-IL-12 is designed to reduce the toxicity associated with systemic IL-12 while enhancing the long-term potency and persistence of TmodTM. The first A2B543 patient was enrolled to dose level 1 in January 2026, and dose escalation continues. A2B543 has received Fast Track Designation from the FDA.

A third A2 Bio poster presentation during ASCO (Free ASCO Whitepaper) 2026 describes modules based on IL-12 and other molecules that boost potency and preserve selectivity of TmodTM-based precision cell therapies.

Poster Presentation Details

Abstract Title

Presenting Author

Abstract Number

Poster Board Number

Poster Presentation Date/Time

Poster Session

Initial safety and efficacy of A2B694, a logic-gated mesothelin (MSLN)-targeted Tmod chimeric antigen receptor T-cell (CAR T) therapy in patients with advanced solid tumors with HLA-A*02 loss of heterozygosity (LOH)

Julian R. Molina, M.D., Ph.D.

Mayo Clinic
Rochester, Minn.

8579

369

Sunday, May 31, 2026

9:00 AM-12:00 PM CDT

Lung Cancer—Non- Small Cell Metastatic

A logic-gated chimeric antigen receptor T-cell (CAR T) therapy with an armored, membrane-tethered IL-12 booster in patients with advanced solid tumors with HLA-A*02 loss of heterozygosity (LOH): EVEREST-2, a Phase 1/2 study

Salman R. Punekar, M.D.

NYU Langone Health
New York

TPS2673

459a

Saturday, May 30, 2026

1:30 PM-4:30 PM CDT

Developmental Therapeutics— Immunotherapy

Influence of onboard, tethered IL-12 on potency of the Tmod NOT gate and selectivity

Jushen Liang

A2 Biotherapeutics
Agoura Hills, Calif.

2562

352

Saturday, May 30, 2026

1:30 PM-4:30 PM CDT

Developmental Therapeutics— Immunotherapy

Full abstracts are available online on the ASCO (Free ASCO Whitepaper) website.

About EVEREST-2

The EVEREST-2 master protocol (NCT06051695) is a seamless Phase 1/2 study evaluating the safety and efficacy of A2B694 (Arm 1) and A2B543 (Arm 2), autologous logic-gated investigational cell therapies developed from the A2 Bio proprietary Tmod platform. The Tmod platform provides selective killing of tumor cells and protection of normal cells via a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. A2B694 consists of an activator that targets MSLN and a blocker that targets HLA-A*02. HLA-A*02 is lost in tumor cells and present in normal cells in the eligible patient population. A2B543 contains the same Tmod construct as A2B694 with an added mem-IL-12 booster. The EVEREST-2 study is recruiting patients with colorectal cancer, pancreatic cancer, non-small cell lung cancer, ovarian cancer, mesothelioma, and other solid tumors that express MSLN and have lost HLA-A*02 expression.

About the Tmod Platform

Invented at A2 Bio, the TmodTM platform is a precision-targeting cellular system, designed with logic-gate technology to enable immune cells to unequivocally differentiate tumors from normal tissues. The system consists of activator and blocker receptors. The activator recognizes antigens on tumor cells and triggers their destruction, while the blocker recognizes antigens on normal cells and protects them. This novel blocker technology enables precise, personalized, and effective T-cell targeting specifically against tumors.

For more information about A2 Bio clinical studies and how to enroll, visit www.a2bioclinicaltrials.com.

(Press release, A2 Biotherapeutics, MAY 21, 2026, View Source [SID1234665974])

On May 21, 2026 Researchers from City of Hope, one of the largest and most advanced cancer research and treatment organizations in the United States with its National Medical Center ranked among the nation’s top cancer centers by U.S. News & World Report, reported it will present new findings at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, where the cancer center will showcase 49 abstracts spanning solid tumors and blood cancers.

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This year’s research, to be presented in Chicago from May 29 to June 2, reflects growing efforts to tailor cancer treatment based on tumor biology, prior therapies and patient-specific factors that influence response.

"Cancer care is entering a new phase where understanding the biology of each patient’s disease is just as important as the treatment itself," said Marcel van den Brink, M.D., Ph.D., City of Hope chief physician executive. "The research we are presenting at ASCO (Free ASCO Whitepaper) demonstrates how precision medicine is becoming a reality across cancer types, and how we can use that insight to deliver smarter therapies, improve outcomes and move the field forward."

City of Hope featured oral presentations

4519: Gut microbiome patterns linked to response to immunotherapy in advanced kidney cancer
7007: Targeted antibody combination shows improved outcomes in patients with relapsed large B-cell lymphoma (SUNMO study subgroup analysis)
4015: Experimental therapy targeting a key cancer growth pathway in advanced liver cancer
5014: First-in-human study of a novel targeted therapy for advanced prostate cancer
Microbiome insights may help predict immunotherapy benefit in kidney cancer

City of Hope researchers report that gut microbiome composition may influence how patients respond to immunotherapy combinations in metastatic renal cell carcinoma, pointing to a potential biomarker that could help guide treatment selection in the future.

The microbiome is a rising focus at City of Hope, highlighted by a recent symposium that convened federal health leaders and top cancer centers to accelerate progress in the field.

The study findings come from a combined analysis of two randomized phase 1 trials evaluating standard-of-care immune checkpoint inhibitor regimens with or without the addition of CBM5881, a live biotherapeutic designed to modulate the gut microbiome. The trials enrolled treatment-naïve patients with metastatic disease who received either nivolumab plus ipilimumab or nivolumab plus cabozantinib, reflecting commonly used immunotherapy-based frontline options.

Across the combined dataset, patients who received CBM588 in addition to immunotherapy achieved an objective response rate of 66.7%, compared with 20% among those receiving standard therapy alone. Median progression-free survival improved to 32.1 months with the combination versus 3.7 months with standard treatment.

Researchers also used a metagenomic measure called TOPOSCORE to assess gut imbalance and found that patients with a more disrupted microbiome saw the greatest benefit. In this subgroup, progression-free survival increased from 2.8 months to 24.9 months with the addition of CBM588. The association between microbiome profile and treatment response was particularly evident in patients who received nivolumab plus ipilimumab, suggesting that the microbiome may interact differently depending on the immunotherapy backbone.

The new data support a growing body of research linking the gut microbiome to immune response.

"These findings suggest the microbiome may play a direct role in shaping immunotherapy outcomes," said Rahul Winayak, M.D., postdoctoral fellow at City of Hope. "If validated in larger studies, this approach could help guide treatment decisions and improve outcomes for patients with kidney cancer."

A randomized phase 3 trial is underway to further evaluate this strategy.

Bispecific antibody combination improves outcomes for patients with lymphoma, including in earlier lines of therapy

Updated data from the phase 3 SUNMO trial continue to show that the combination of mosunetuzumab, a bispecific antibody, and polatuzumab vedotin, an antibody-drug conjugate, improves outcomes for patients with relapsed or refractory large B-cell lymphoma who are not eligible for autologous stem cell transplant.

The study randomized patients to receive the combination regimen or standard chemotherapy with rituximab, gemcitabine and oxaliplatin. With a median follow-up of more than two years, the combination demonstrated an objective response rate of 70.3%, compared with 40.0% for standard therapy, along with a significant reduction in the risk of disease progression.

A key focus of this updated analysis was outcomes by line of therapy. Among patients who received treatment in the second-line setting, the combination produced higher response rates, deeper remissions and longer durations of response compared with both later-line patients and those who received chemotherapy. Median progression-free survival and duration of complete response were not reached in several subgroups, underscoring the durability of benefit.

The safety profile remained stable with longer follow-up, with low rates of higher-grade cytokine release syndrome and no observed neurotoxicity. These findings support use of this novel regimen in patients who are unable to tolerate aggressive chemotherapy.

"These results support the growing role of bispecific antibody-based combinations as an alternative to traditional chemotherapy," said Elizabeth Budde2, M.D., Ph.D., executive medical director of the Enterprise Immune Effector Cell Program at City of Hope. "We are especially encouraged by the durability of responses in earlier lines of therapy, where improving long-term outcomes is critical for every patient."

New therapy targeting a key cancer growth pathway shows promise in advanced liver cancer

City of Hope investigators are evaluating tegavivint, a first-in-class small-molecule inhibitor that targets the Wnt/β-catenin signaling pathway, a key driver in many liver cancers that have historically been difficult to treat.

The ongoing phase 1/2 study includes patients with advanced hepatocellular carcinoma who have received at least one prior line of systemic therapy and have disease that cannot be treated with surgery or localized therapies.

Among patients with Wnt pathway mutations detected with molecular profiling and treated within the recommended dose range, the therapy demonstrated clinical activity, with an objective response rate of 22%, disease control rate of 89% and median progression-free survival of eight months in patients treated earlier in their disease course.

Importantly, the study showed evidence of target engagement, including reductions in alpha-fetoprotein levels and changes in Wnt pathway circulating tumor DNA allele frequency. These findings suggest that the drug is affecting the intended biological pathway, a key challenge in prior efforts to target Wnt signaling.

"Targeting the Wnt pathway has long been a major challenge in oncology, but these data suggest we may finally be making progress," said Daneng Li, M.D., gastrointestinal medical oncologist at City of Hope. "With further validation, this approach could meaningfully expand treatment options and provide a potential targeted therapy approach to improve outcomes for patients with advanced liver cancer."

First-in-human study shows early activity for novel prostate cancer therapy

City of Hope researchers are presenting early results from a first-in-human study of ABBV-969, a dual-targeting antibody-drug conjugate that binds PSMA and STEAP1, two proteins commonly found in advanced prostate cancer. The therapy is designed to deliver a potent anti-cancer agent directly to tumor cells expressing PSMA and/or STEAP1 antigens.

The phase 1 study enrolled patients with metastatic castration-resistant prostate cancer who had received multiple prior lines of therapy, including androgen receptor pathway inhibitors and taxane-based chemotherapy to stop cell division. Patients were treated across a range of dose levels to evaluate safety, pharmacokinetics and preliminary efficacy.

Among patients with measurable disease, the therapy achieved an objective response rate of 45%, with responses observed across multiple dose levels starting at 3 mg/kg. Reductions in prostate-specific antigen (PSA) levels were also common, with 67% of patients achieving a PSA50 response and 28% achieving deeper PSA declines of 90% or greater.

The study assessed a range of doses and dose optimization is ongoing. The study also demonstrated a manageable safety profile. The most common higher-grade adverse events were hematologic, including anemia, which were generally reversible and consistent with the drug’s mechanism of action.

"We are seeing early signals that this targeted approach can deliver meaningful responses, even in heavily pretreated patients," said Tanya Dorff3, M.D., F.A.S.C.O., genitourinary medical oncologist at City of Hope. "The next step will be to better understand how to position this therapy to further improve outcomes."

(Press release, City of Hope, MAY 21, 2026, View Source [SID1234665973])