botensilimab (AGEN1181) / Agenus, Zydus Lifesciences - LARVOL DELTA

A progress report for a Phase 1b/2 study of ENPP1 inhibitor, vizenpistat in combination with botensilimab and balstilimab in subjects with refractory metastatic microsatellite stable colorectal cancer (AACR 2026) - "Abstract is embargoed at this time."

Clinical • Combination therapy • Metastases • P1/2 data • Colorectal Cancer • Oncology • Solid Tumor • ENPP1

Preliminary results of first-line botensilimab (BOT) and balstilimab (BAL) optimization in microsatellite stable colorectal cancer (MSS CRC) without liver, bone, or brain metastasis (BBOpCo) (AACR 2026) - "Abstract is embargoed at this time."

Clinical • Colorectal Cancer • Oncology • Solid Tumor

A phase II study of agenT-797, botensilimab (BOT) and balstilimab (BAL) in PD-1 refractory gastroesophageal cancer (GEC) (AACR 2026) - "Abstract is embargoed at this time."

P2 data • Gastroesophageal Cancer • Oncology • Solid Tumor • PD-1

Agenus to Host March 2026 Stakeholder Webcast Harnessing the Immune System to Advance BOT + BAL Across Tumor Types and Expand Patient Access (Agenus Inc. Press Release) - "Dr. Armen will open the session by discussing Agenus’ mission to harness the immune system across tumor types and the urgency of advancing new options for patients with historically treatment-resistant cancers. He will also outline key priorities for 2026 as momentum continues to build across the BOT+BAL program. Dr. O’Day will provide a clinical perspective on the durability and consistency of BOT+BAL across tumor types, including in historically immunotherapy-resistant cancers. He will also highlight how these data are informing ongoing development and later-stage trials."

Clinical • Oncology

Molecular complete response to the RIN protocol (regorafenib, ipilimumab, and nivolumab) in a patient with advanced recurrent metastatic mismatch repair proficient/microsatellite stable (pMMR/MSS) rectal cancer. (PubMed, Ther Adv Med Oncol) - "Rectal cancer recurrence remains a major therapeutic challenge, particularly in patients unresponsive to conventional regimens. While previous studies have demonstrated limited benefit of immunotherapy in this tumor subtype, the present findings suggest an emerging therapeutic opportunity that warrants prospective evaluation to confirm efficacy, explore the mechanistic basis, and identify biomarkers predictive of durable response beyond the absence of liver metastases. More effective combinatorial regimens like zanzalintinib and atezolizumb (STELLAR-303) trial, as well as newer generation of CTLA-4 inhibitors like botensilimab, vilastobart, and muzastotug are showing more promise for patients with MSS colorectal cancers in particular who do not have liver metastases (NLM)."

IO biomarker • Journal • Mismatch repair • pMMR • Colorectal Adenocarcinoma • Colorectal Cancer • Embryonal Tumor • Immune Modulation • Immunology • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor • CEACAM5 • KRAS

Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial. (PubMed, Nat Med) - P1 | "The combination of BOT plus BAL demonstrated a manageable safety profile with no new immune-mediated safety signals and encouraging clinical activity with durable responses. ClinicalTrials.gov identifier: NCT03860272 ."

Journal • Metastases • P1 data • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Oncology • Solid Tumor • CTLA4

Botensilimab (Fc-enhanced anti-CTLA-4 antibody) plus balstilimab (anti-PD-1 antibody) in patients with treatment-refractory ovarian cancer. (PubMed, J Immunother Cancer) - "The BOT/BAL combination demonstrated deep, durable responses and complete remissions in patients with treatment-refractory ovarian cancer where no standard treatments are currently available. RECIST under-represented clinical benefit with 11 patients achieving prolonged/clinically meaningful stable disease (or better) for ≥24 weeks. Toxicities were manageable and reversible. The encouraging clinical activity of BOT/BAL in heavily pretreated patients, as well as biomarker associations, warrants further investigation of this combination."

IO biomarker • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • ITGAX

Pre-operative Targeted Treatments in Molecularly Selected Resectable Colorectal Cancer (UNICORN) (clinicaltrials.gov) - P2 | N=197 | Recruiting | Sponsor: Gruppo Oncologico del Nord-Ovest | N=140 ➔ 197

Enrollment change • Colorectal Cancer • Oncology • Solid Tumor • BRAF • EGFR • HER-2 • KRAS • MET • MSI • POLD1 • POLE • TMB

Botensilimab: Expiry of patents in US/EU in 2037 (Agenus Inc.) - Annual Report 2025

Patent • Oncology • Solid Tumor

Neoadjuvant botensilimab plus balstilimab in MMR proficient and deficient early stage cancers: First results of the pan-cancer NEOASIS study (AACR 2025) - "Data of the safety run-in of 20 pts show that neoadjuvant bot/bal was safe and did not lead to surgical delays. In addition, the observed pathological responses are encouraging and suggest a potential for neoadjuvant immunotherapy using bot/bal across tumor types, including pMMR BC and sarcoma. Accrual in efficacy baskets for both dMMR and pMMR tumors is currently ongoing at the bot 50mg dose level."

Clinical • Pan tumor • Breast Cancer • Colorectal Cancer • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Sarcoma • Skin Cancer • Small Intestinal Carcinoma • Solid Tumor • Triple Negative Breast Cancer

Agenus…announced that preliminary results from an investigator-sponsored study evaluating botensilimab (BOT) in combination with balstilimab (BAL) in first-line microsatellite stable colorectal cancer (MSS CRC) will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 (Businesswire) - "The BBoPCO study (Botensilimab and Balstilimab Optimization in Colorectal Cancer; NCT06268015) is the first trial of its kind to advance a combination immunotherapy approach in the first-line setting for MSS mCRC, evaluating BOT+BAL in patients without liver, bone, or brain metastases-a population historically resistant to immunotherapy."

P2 data • Colorectal Cancer

France Expands National AAC Access for Agenus’ Botensilimab + Balstilimab for Ovarian Cancer and Soft-Tissue Sarcomas (Businesswire) - "The updated protocol expands France’s previously granted AAC authorization for BOT+BAL in patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases to eligible patients with certain ovarian cancers and soft-tissue sarcomas-diseases with substantial unmet medical need after standard options have been exhausted. The revised protocol is designed to broaden the eligibility criteria, allowing more patients with advanced solid tumors to have early access to BOT+BAL under reimbursed compassionate use....For eligible French patients treated in hospital under AAC, BOT+BAL is fully reimbursed."

Clinical protocol • Platinum resistant • Reimbursement • Colorectal Cancer • Ovarian Cancer • Soft Tissue Sarcoma

Phase 3 BATTMAN MSS mCRC Registrational Trial Initiated (Businesswire) - "The study is expected to enroll approximately 830 patients across more than 100 sites in Canada, France, Australia and New Zealand through leading cooperative group networks and is designed to support potential regulatory filings in the United States, Europe, Canada and other geographies."

MSI-H • pMMR • Trial status • Colorectal Cancer • Microsatellite Instability

Outside France, BOT+BAL may be available in select countries through paid named-patient programs where permitted by local regulations and initiated at the request of treating physicians. (Businesswire) - "Depending on local requirements, access may involve out-of-pocket payment and/or special insurance arrangements."

Commercial • Oncology

NEOASIS: Pan-tumor Neoadjuvant Basket Study of Immune Check-point Inhibition and Novel Immuno-oncology Combinations (clinicaltrials.gov) - P2/3 | N=133 | Recruiting | Sponsor: The Netherlands Cancer Institute | N=92 ➔ 133

Enrollment change • Pan tumor • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

CIME/ET23-185: Study aiming to compare the survival of patients with locally advanced or metastatic MSI/dMMR Esogastric adenocarcinomas treated by a combination of Immune checkpoint inhibitors (botensilimab + balstilimab) versus the standard of care (FOLFOX/XELOX + nivolumab) (clinicaltrialsregister.eu) - P2/3 | N=132 | Recruiting | Sponsor: Centre Leon Berard | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • dMMR • Enrollment open • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Microsatellite Instability • Oncology • Solid Tumor • HER-2 • MSI • PD-L1

Systemic and tumor-microenvironment inflammation shape outcomes in patients with immunologically cold, treatment-refractory tumors treated with Fc-enhanced anti–CTLA-4 botensilimab (AACR-IO 2026) - P1 | "Botensilimab (BOT), a novel Fc-enhanced anti–CTLA-4 antibody, alone or combined with balstilimab (BAL; anti–PD-1), has demonstrated promising clinical activity across immunologically “cold” treatment-refractory cancers. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr B036."

Biomarker • Clinical • IO biomarker • Tumor microenvironment • Tumor mutational burden • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • CD4 • CD8 • CRP • IFNG • IL17A • IL6 • PD-L1 • TMB

Agenus Triggers First $20M Contingent Payment Under Zydus Life Sciences Collaboration to Support BOT+BAL Manufacturing Needs (Businesswire) - "These activities will allow Zydus to perform the initiation of its commercial supply of Agenus’ lead programs...Until marketing authorization is granted, BOT+BAL is accessible only through clinical trials including the Phase 3 BATTMAN trial in refractory MSS colorectal cancer and authorized early access mechanisms where permitted and available under each country’s regulatory framework...For eligible French patients treated in hospital under AAC meeting the pre-defined criteria, BOT+BAL is fully reimbursed by France’s national health system (Assurance Maladie)."

Commercial • Reimbursement • Colorectal Cancer

BATTMAN: Botensilimab + Balstilimab vs Best Supportive Care as Therapy in Chemo-refractory, Unresectable, Colorectal Adenocarcinoma (clinicaltrials.gov) - P3 | N=834 | Recruiting | Sponsor: Canadian Cancer Trials Group | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor

Pilot Study of an Implantable Microdevice for In Situ Evaluation of Drug Response in Patients With Colorectal Liver Metastasis (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Northwell Health | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor

Agenus…announced new translational and clinical biomarker data from its Phase 1b C-800-01 trial (NCT03860272) evaluating botensilimab (BOT), an Fc-enhanced anti–CTLA-4 antibody, in combination with balstilimab (BAL), an anti–PD-1 antibody (Businesswire) - "The retrospective analyses demonstrate that survival with BOT+BAL is associated with the balance of two opposing biological factors: systemic inflammation in the blood (associated with poorer outcomes) and tumor immune activity within the tumor microenvironment (TME) (associated with more favorable outcomes)....In 341 efficacy-evaluable patients with advanced, treatment-refractory cancers and available biomarker data (data cutoff December 13, 2025): Objective response rate (ORR): 17%; Clinical benefit rate (CBR): 26%; Median overall survival (OS): 17.2 months; 24-month overall survival rate: 38%....Clinical activity was observed across tumor types commonly considered immunologically 'cold', including MSS mCRC, ovarian cancer, sarcoma, and PD-1 relapsed or refractory non-small cell lung cancer."

Biomarker • P1 data • Retrospective data • Colorectal Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Sarcoma

A phase II study of agenT-797 (invariant natural killer T-cells), botensilimab (Fc-enhanced CTLA-4 inhibitor) and balstilimab (anti-PD-1) in patients with advanced, refractory gastroesophageal adenocarcinoma. (ASCO-GI 2025) - "Given their complementary mechanisms of action in modulating anti-tumor immunity, we aimed to evaluate the safety and efficacy of combining BOT, BAL, and agenT-797 with standard ramucirumab (anti-vascular endothelial growth factor receptor-2 antibody) and paclitaxel chemotherapy in patients with advanced EG cancer who have progressed on frontline therapy. To date, 12 patients have been enrolled and started on treatment. This trial is registered with ClinicalTrials.gov, NCT06251793."

Clinical • Metastases • P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • KDR

Neoadjuvant botensilimab (BOT) plus balstilimab (BAL) in resectable mismatch repair proficient (pMMR) and deficient (dMMR) colorectal cancer (CRC): NEST clinical trial update. (ASCO-GI 2025) - P2 | "Neoadjuvant BOT/BAL is safe, with no delays to surgery, and effective. We observed high MPR rates in both MSS and MSI-H CRC with no recurrences to date. The MPR and pCR rate improved with extended time to surgery."

Clinical • Mismatch repair • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor • MSI

Monitoring botensilimab- and balstilimab-induced T-cell dynamics in refractory mismatch repair proficient metastatic colorectal cancer. (ASCO 2025) - P2 | "In this trial patients were randomized into BOT (75mg or 150mg Q6W, 4x) monotherapy or in combination with BAL (240mg Q2W, for 2 years), versus standard of care (regorafenib or trifluridine/tipiracil). Deep T cell repertoire profiling detected dynamics of circulating T cells with quantitative and qualitative difference related to ICI response. Immune cell tracking from liquid biopsies is a powerful tool to quantify ICI efficacy in real time."

IO biomarker • Metastases • Mismatch repair • pMMR • Colorectal Cancer • Hepatology • Oncology • Solid Tumor

Doxorubicin Plus Dual Checkpoint Blockade for Soft Tissue Sarcomas (clinicaltrials.gov) - P2 | N=65 | Recruiting | Sponsor: University of Colorado, Denver | Trial completion date: Nov 2026 ➔ Dec 2027 | Trial primary completion date: Nov 2025 ➔ Apr 2027

Checkpoint inhibition • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor