balstilimab (AGEN2034) / Agenus, Betta Pharma, Zydus Lifesci - LARVOL DELTA

KRAS-Targeted Vaccine Combined With Balstilimab and Botensilimab for Patients With Stage IV MMR-p Colorectal Cancer and Pancreatic Ductal Cancer (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Nov 2028 ➔ Jul 2029 | Trial primary completion date: Nov 2028 ➔ Mar 2028

Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

DOXORUBICIN PLUS BOTENSILIMAB, A NEXT GENERATION CTLA4 INHIBITOR, WITH OR WITHOUT BALSTILIMAB, A PD1 INHIBITOR, IN PATIENTS WITH ADVANCED SOFT TISSUE SARCOMAS (CTOS 2025) - P2 | "We hypothesized that concurrent doxorubicin (DOX) would improve STS immunogenicity and boost efficacy of ICIs, including BOT with or without BAL. We expanded a previously reported Phase 2 trial of DOX plus first-generation CTLA4 inhibitor zalifrelimab (ZAL) plus BAL (NCT04028063). DOX with BOT +/- BAL exhibits safety and efficacy consistent with prior experience of DOX/ZAL/BAL. Further investigation is needed to determine biomarkers of response/resistance and the optimal timing/sequence of DOX/ICIs to further improve outcomes."

Clinical • IO biomarker • Metastases • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Agenus to Host End-of-Year Stakeholder Webcast Featuring GI Oncology Leaders and Progress of BOT/BAL (Businesswire) - "The session will feature leading experts in gastrointestinal oncology and patient advocates discussing progress with the BOT/BAL program, emerging clinical insights, and the evolving treatment landscape for colorectal cancer....Dr. Jonathan Loree will provide an update on the global Phase 3 BATTMAN study, including site engagement, operational readiness, and early feedback from investigators supporting strong trial momentum heading into 2026."

Clinical data • Trial status • Colorectal Adenocarcinoma

A Study of Botensilimab and Balstilimab for Colorectal Cancer (clinicaltrials.gov) - P2 | N=284 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

Circulating tumor DNA • New P2 trial • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

NCI-2022-09458: FOLFOX and Bevacizumab in Combination With Botensilimab and Balstilimab (3B-FOLFOX) for the Treatment of Microsatellite Stable (MSS) Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=20 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Oct 2025 ➔ Jun 2026 | Trial primary completion date: Oct 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Solid Tumor • POLE

Upcoming Catalysts (Businesswire) - "BATTMAN patient enrollment to commence before year-end 2025...Investigator‑initiated trials: Neoadjuvant and frontline data updates expected 1H 2026; France AAC: Will generate real world evidence."

Clinical data • Enrollment status • Colorectal Adenocarcinoma

Botensilimab, Balstilimab and Regorafenib for the Treatment of Patients With Microsatellite Stable Metastatic Colorectal Cancer Who Have Progressed on Prior Chemotherapy (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial primary completion date: Oct 2025 ➔ May 2025

Trial primary completion date • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • BRAF • PD-L1

A mutant KRAS peptide vaccine (mKRAS-VAX) combined with immune checkpoint blockade recruits vaccine-induced T-cells into metastatic MMRp/MSS colorectal tumors (SITC 2025) - P1 | "We conducted a Phase 1 (NCT04117087) study of mKRAS-VAX with nivolumab and ipilimumab in patients with MMRp/MSS mCRC refractory to fluoropyrimidines, irinotecan, and oxaliplatin...A Phase 1b trial (NCT06411691) combining mKRAS-VAX with ICIs balstilimab and botensilimab in advanced MMRp/MSS CRC and pancreatic ductal adenocarcinoma is underway.Trial Registration The study was registered at ClinicalTrials.gov (NCT04117087).Ethics Approval The study protocol and all amendments were approved by the institutional review board at Johns Hopkins University (IRB00210915). The study was conducted in accordance with the Declaration of Helsinki and good clinical practice guidelines. All participants provided written informed consent."

Checkpoint block • Checkpoint inhibition • IO biomarker • Metastases • Colorectal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • IFNG • KRAS • TRB

A phase I trial of botensilimab, balstilimab and regorafenib (BBR) in chemotherapy-resistant patients with microsatellite stable (MSS) metastatic colorectal cancer (ESMO 2025) - P1/2 | "Although prolonged disease stabilization was seen at the RP2D, the study did not meet efficacy thresholds for expansion. Responses in pts with LmCRC were noted in instances of limited hepatic mCRC and may reflect a subgroup that is more immune responsive."

Clinical • Metastases • P1 data • Colorectal Cancer • Oncology • Solid Tumor

Vorbipiprant (CR6086) / Balstilimab (AGEN2034) Combination in Stage IV Refractory pMMR - MSS CRC, and Other Metastatic GI Cancers (clinicaltrials.gov) - P1/2 | N=107 | Active, not recruiting | Sponsor: Rottapharm Biotech | Recruiting ➔ Active, not recruiting

Enrollment closed • Mismatch repair • pMMR • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF

Emerging survival plateaus with botensilimab and balstilimab: Pan tumor data from a large phase Ib trial of advanced solid tumors (ESMO 2025) - P1 | "Notably, imAEs / discontinuations correlated with improved survival. These pan tumor late-stage data complement the emerging pan tumor neoadjuvant data, further leveraging the power of BOT + BAL."

Metastases • P1 data • Pan tumor • Colorectal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor

Efficacy and safety of balstilimab with or without zalfrelimab in recurrent cervical cancer: Results from the global phase II RaPiDs trial (ESMO 2025) - P2 | "Median age 47 yrs (range 25–80); prior treatments, 100% platinum, 89% taxane, 85% radiotherapy, 39% bevacizumab. Conclusions BAL ± ZAL demonstrated durable responses independent of PD-L1 status by both investigator assessment and BICR in pts with recurrent cervical cancer. BAL ± ZAL therapy warrants further investigation as an alternative treatment option, particularly for PD-L1 negative pts."

Clinical • P2 data • Cervical Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PD-L1

A phase II, open label study to evaluate the safety and clinical activity of balstilimab in patients with advanced/metastatic non-melanoma skin cancers (AGENONMELA) (ESMO 2025) - "Table: 1662P Baseline Pts characteristics N (%) CBR at 12 weeks N (%) Overall 32 (100) 20 (64.5) Sex Female 12 (37.5) 4 (33.3) Male 20 (62.5) 16 (84.2) Histology Basal cell carcinoma (BCC) 8 (25) 7 (87.5) Squamous cell carcinoma 4 (12.5) 1 (25) Adnexal adenocarcinoma 6 (18.8) 4 (66.7) Angiosarcoma 6 (18.8) 2 (33.3) Other 8 (25): Kaposi's sarcoma 3 (9.4) Gorlin-associated BCC 2 (6.3) Extramammary Paget 2 (6.3) Adenoid cystic carcinoma 1 (3.1) 6 (85.7) Stage Locally advanced 25 (78.1) 15 (62.5) Metastatic 7 (21.9) 5 (71.4) Systemic treatment lines 0 14 (43.8) 7 (53.8) 1 14 (43.8) 10 (71.4) 2 3 (9.4) 2 (66.7) 3 1 (3.1) 1 (100) Conclusions Balstilimab showed promising activity and an acceptable safety profile in advanced NMSC, supporting further investigation of PD-1 blockade in this heterogenous population. Legal entity responsible for the study AGENONMELA study group."

Clinical • Metastases • P2 data • Adenoid Cystic Carcinoma • Angiosarcoma • Basal Cell Carcinoma • Kaposi Sarcoma • Non-melanoma Skin Cancer • Oncology • Sarcoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma

Dual CTLA 4 and PD 1 Blockade With Botensilimab and Balstilimab Demonstrates Durable Survival in Refractory Solid Tumors (OncoDaily) - "Objective Response Rate (ORR): 17% (95% CI 13–21), consistent across both BOT doses; Median Duration of Response: 15 months (range 10 – not reached); Clinical Benefit Rate (CR + PR + SD ≥ 24 weeks): 26%; Median Overall Survival (mOS): 17 months (95% CI 14–21); 24-month OS rate: 39% (95% CI 32–45), showing the emergence of long-term survival plateaus."

P1 data • Colorectal Cancer • Hepatocellular Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Sarcoma

Agenus to Host October Stakeholder Briefing Showcasing BOT/BAL Global Momentum and Post-ESMO Insights (Agenus Inc. Press Release) - "Dr. Gordon will discuss results from his oral presentation at the European Society for Medical Oncology (ESMO) Congress 2025, featuring data from over 400 patients treated with BOT/BAL across multiple refractory solid tumors."

P1 data • 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 | Not yet recruiting | Sponsor: Northwell Health

New P1 trial • Colorectal Cancer • Oncology • Solid Tumor

At #DAVAGI, @DrElkhoueiry ( @uscnorris ) presented Phase I/Ib data of botensilimab(CTLA-4) + balstilimab(PD-1) in refractory HCC. In pts with ≥2 prior lines & progression post-ICI, median OS was 12.3 mo (95% CI 8.4–21.4), showing early signal of activity.

Clinical

Balstilimab + Botensilimab: "BOT/BAL demonstrates deep, durable responses in advanced MSS CRC"; Colorectal cancer (Agenus Inc.) - Corporate Presentation

P1 data • Colorectal Cancer • Oncology

France Grants Reimbursed Compassionate Access (AAC) for Agenus’ BOT/BAL in Refractory MSS Metastatic Colorectal Cancer (Agenus Inc. Press Release) - "The French National Agency of Medicines and Health Products Safety’s (ANSM) listings for botensilimab and balstilimab are live and detail eligibility (including MSS and no active liver metastases) and dosing. BOT/BAL remains investigational and is not approved for commercial marketing in France or elsewhere."

Reimbursement • Colorectal Cancer

Agenus Announces Second Quarter 2025 Financial Results and Virtual Meeting to Discuss Strategic Progress (Businesswire) - "Key 2H 2025 Catalysts: (i) In Q4 2025, initiate the global BATTMAN Phase 3 trial of BOT/BAL in refractory MSS CRC in partnership with the Canadian Clinical Trials Group (CCTG)...; (ii) Share new BOT/BAL clinical results in colorectal and other solid tumors at major oncology congresses in Q4 2025."

Clinical data • New P3 trial • Colorectal Cancer

Agenus to Unveil BOT/BAL Strategic Advancements, Key Milestones, and Future Outlook in Virtual Stakeholder Briefing on August 27, 2025 (Businesswire) - "The agenda includes...recent data from the botensilimab (BOT) and balstilimab (BAL) program, and an overview of the Phase 3 BATTMAN study in metastatic CRC-plus highlights of upcoming milestones and potential breakthroughs in immuno-oncology."

Clinical data • New P3 trial • Colorectal Cancer

Botensilimab, Balstilimab, and SBRT in Colorectal Cancer (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Massachusetts General Hospital

MSI-H • New P1 trial • pMMR • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor

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

New P3 trial • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor

NEST-1: Combination Immunotherapy in Colorectal Cancer (clinicaltrials.gov) - P2 | N=36 | Suspended | Sponsor: Weill Medical College of Cornell University | Trial completion date: Dec 2025 ➔ Jun 2026 | Recruiting ➔ Suspended | Trial primary completion date: May 2025 ➔ Nov 2025

Trial completion date • Trial primary completion date • Trial suspension • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

Agenus to Highlight Emerging Survival Plateaus with Botensilimab/Balstilimab in Oral Presentation of Study in Refractory Patients Across Five Tumor Types at ESMO 2025 (Businesswire) - "Agenus...announced that four abstracts highlighting clinical progress across its botensilimab and balstilimab immunotherapy programs have been accepted for presentation at the European Society for Medical Oncology (ESMO) Congress 2025....The highlight is an oral presentation that will feature emerging survival plateaus from a study of botensilimab plus balstilimab in 343 evaluable patients with refractory metastatic solid tumors across five tumor types. Three additional poster presentations will feature data from investigator-sponsored studies in cervical cancer, MSS metastatic colorectal cancer (mCRC), and non-melanoma skin cancers, underscoring the broad potential of botensilimab and balstilimab based combinations in difficult-to-treat cancers."

Clinical data • Cervical Cancer • Colorectal Cancer • Non-melanoma Skin Cancer