Regorafenib

LEXINGTON, Mass.--(BUSINESS WIRE)--Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, today announced three-year landmark Phase 1b data from the fully enrolled C-800-01 cohort evaluating botensilimab (BOT), an Fc-enhanced multifunctional anti–CTLA-4 antibody, plus balstilimab (BAL), an anti–PD-1 antibody, in patients with refractory microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases. The data were presented at the European Society for Medical Oncology Gastrointestinal Cancers (ESMO GI) Congress 2026 on July 2 in Munich, Germany. With longer follow-up, we are seeing the elements that matter for a potentially differentiated immunotherapy regimen: durable survival, sustained responses, treatment-free intervals, and a manageable safety profile. BOT+BAL demonstrated clinically meaningful long-term survival in a heavily pretreated patient population with historically limited benefit from conventional immune checkpoint inhibitors and few durable treatment options after progression on standard therapies. With extended follow-up, median overall survival was 21.2 months and the three-year overall survival rate was 33%, with the Kaplan-Meier curve showing a plateau beyond two years. Available later-line standards in refractory MSS mCRC without active liver metastases have historically reported median overall survival of approximately 10–14 months in relevant analyses, reflecting a treatment setting in which few patients have historically remained alive at later landmark timepoints and pivotal studies have generally focused on median survival rather than mature 36-month overall survival outcomes.i In this context, the survival profile, curve plateau beyond two years, and proportion of patients alive and off systemic anticancer therapy support the durability of benefit observed with BOT+BAL in this fully enrolled 123-patient Phase 1b cohort. The data build on the two-year overall survival results presented by Dr. Benjamin L. Schlechter of Dana-Farber Cancer Institute at ESMO GI 2025 and reflect an additional year of follow-up from the same cohort. With longer follow-up, the dataset now includes 26 confirmed responses; median duration of response was not reached; and 21 patients, or 17%, were alive and off all systemic anticancer therapy at last follow-up, including 13 responders. “These three-year data are important because they show a pattern of benefit that is not typically expected in refractory MSS colorectal cancer,” said Benjamin L. Schlechter, M.D., of Dana-Farber Cancer Institute and presenting author of the study. “These are patients who had received multiple prior lines of therapy and had few remaining options. Seeing a subset of patients remain alive and off systemic anticancer therapy after treatment speaks to the clinical relevance of these results and the potential for botensilimab plus balstilimab to change expectations for what immunotherapy may achieve in this setting.” “BOT+BAL is not simply another checkpoint combination; it was designed to activate antitumor immunity in tumors that have been difficult to reach with conventional immunotherapy,” said Steven O’Day, M.D., Chief Medical Officer of Agenus. “With longer follow-up, we are seeing the elements that matter for a potentially differentiated immunotherapy regimen: durable survival, sustained responses, treatment-free intervals, and a manageable safety profile. These findings strengthen the foundation for BATTMAN and our broader development strategy in MSS colorectal cancer.” The Phase 1b (NCT03860272) cohort included 123 patients with MSS mCRC without active liver metastases. Patients had received a median of three prior lines of therapy; 67% had received at least three prior lines, 15% had received prior anti–PD-(L)1 with or without anti–CTLA-4 therapy, and 30% had received at least one later-line regimen of regorafenib, trifluridine/tipiracil with or without bevacizumab, or fruquintinib. Key Efficacy Results: Median overall survival: 21.2 months, with 24-month and 36-month overall survival rates of 41% and 33%, respectively Confirmed objective response rate : 21%, including three complete responses and 23 partial responses Median duration of response: not reached; responses ranged from 1.9 months to at least 37.4 months Disease control rate : 69% at six weeks Clinical benefit rate : 28% at 24 weeks Tumor regression : observed in more than 40% of patients Treatment-free survival: 21 patients or 17%, were alive and off all systemic anticancer therapy, including 13 responders with a subset of patients remaining free from subsequent therapy or death for more than two years In a post hoc late-line–exposed subgroup of 37 patients who had received at least one prior regimen of regorafenib, trifluridine/tipiracil with or without bevacizumab, or fruquintinib, BOT+BAL showed a confirmed objective response rate of 22%, median overall survival of 16.2 months, and a three-year overall survival rate of 30%. In this subgroup, median duration of response was 16.6 months, disease control rate was 70%, and clinical benefit rate at 24 weeks was 27%. Safety Results With extended follow-up, no new safety signals were observed and there were no treatment-related deaths. Immune-mediated diarrhea/colitis resolved in 98% of affected patients, with a median time to resolution of 14 days from onset. Treatment-related immune-mediated diarrhea/colitis was the most common immune-mediated adverse event (42%; grade ≥3, 15%). The selected Phase 3 regimen of BOT 1 mg/kg plus BAL demonstrated improved tolerability, with lower rates of immune-mediated diarrhea/colitis (27%; grade ≥3, 10%) than the 2 mg/kg regimen. Together, the mature efficacy, treatment-free survival, and extended safety findings support continued evaluation of BOT+BAL in MSS mCRC and provide rationale for the ongoing randomized Phase 3 BATTMAN trial evaluating BOT+BAL in refractory MSS/proficient mismatch repair (pMMR) metastatic colorectal cancer. Presentation Details Abstract Title: Botensilimab + Balstilimab in Microsatellite-Stable Metastatic Colorectal Cancer Without Active Liver Metastases: Extended Follow-Up and 3-Year Survival Presenter: Benjamin L. Schlechter, M.D.; Dana-Farber Cancer Institute, Boston, MA, USA Final Publication Number: 91P Congress: European Society for Medical Oncology Gastrointestinal Cancers Congress 2026 Location: ESMO GI, 2026 | Munich, Germany Poster Availability: The poster is available on the Agenus publications page. About the C-800-01 Study (NCT03860272) C-800-01 is a first-in-human Phase 1b clinical trial evaluating botensilimab with or without balstilimab in patients with advanced solid tumors. The MSS mCRC without active liver metastases cohort enrolled 123 patients who received BOT 1 mg/kg or 2 mg/kg every six weeks plus BAL 3 mg/kg every two weeks. The primary endpoint was safety and tolerability. Secondary endpoints included objective response rate, duration of response, disease control rate, and progression-free survival. Exploratory endpoints included overall survival and clinical benefit rate. About Agenus Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants. Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels. About Botensilimab (BOT) Botensilimab (BOT) is a human Fc enhanced multifunctional anti-CTLA-4 antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses. Approximately 1,300 patients have been treated with botensilimab and/or balstilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov. About Balstilimab (BAL) Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in more than 900 patients to date and has demonstrated clinical activity and a favorable tolerability profile in several tumor types. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2025, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.

Full results from Bristol Myers Squibb's Phase III KRYSTAL-10 trial offer a clearer picture of why its chemotherapy-free regimen of Krazati (adagrasib) plus cetuximab failed to confirm its benefit in second-line KRAS G12C-mutated metastatic colorectal cancer (CRC).Presented at the European Society for Medical Oncology Gastrointestinal Cancers (ESMO GI) congress this month, the data showed numerically higher overall response rates (ORR) than standard chemotherapy, but no statistically significant improvement in either progression-free survival (PFS) or overall survival (OS), the trial's dual primary endpoints.Krazati landed in the pharma's portfolio after it bought Mirati Therapeutics for $5.8 billion in early 2024 (see – Vital Signs: BMS's BD blunders come to bear and Vital Signs: BMS outsources its outsourcing).The drug is already cleared for lung cancer, but US regulators granted it an accelerated approval shortly after the Mirati takeout in the second-line CRC setting based on the Phase I/II KRYSTAL-1 trial where it demonstrated a confirmed ORR of 34%.KRYSTAL-10 was meant to confirm Krazati's benefit in CRC. The trial compared the KRAS G12C inhibitor plus cetuximab versus a chemotherapy regimen (either FOLFIRI or modified FOLFOX6) with or without a VEGF-targeted therapy as a second-line treatment in 461 CRC patients with KRAS G12C mutations.According to detailed results presented at ESMO GI, the median PFS was 7.5 months with the targeted combination compared with 8.1 months for chemotherapy, corresponding to a hazard ratio of 0.89 that didn't reach statistical significance (p=0.32). OS was virtually identical between the two groups, at a median 21.6 months and 21.7 months, respectively (HR 0.83; p=0.09).The Krazati regimen did demonstrate greater antitumour response, with nearly half of patients (47%) achieving an objective response versus the chemotherapy arm (16%). Complete responses were also more frequent, occurring in 7% of patients receiving the targeted combination compared with less than 1% among those receiving chemotherapy.Investigators reported no new safety signals; grade 3 to 5 treatment-related adverse events occurred in 46% of patients receiving the targeted regimen and 55% of those receiving chemotherapy.The setback gives Amgen's rival KRAS inhibitor Lumakras (sotorasib) more momentum in the space. Paired with Vectibix (panitumumab), Lumakras won FDA approval in early 2025 for second-line CRC, backed by Phase III CodeBreaK 300 data showing a 52% reduction in risk of progression or death versus investigator's choice of either the chemotherapy regimen Lonsurf (trifluridine/tipiracil) or the kinase inhibitor Stivarga (regorafenib).