- Long-term survival of patients in the 123-patient Phase 1b CRC cohort was not limited to patients with favorable baseline characteristics, suggesting durable benefit may extend across a broader patient population
- Approximately 1 in 4 long-term survivors were alive and off all cancer therapy at last follow-up, with responses lasting more than three years
- Patients with fewer prior lines of treatment were more likely to achieve long-term survival, supporting rationale for BOT+BAL earlier in the course of treatment
LEXINGTON, Mass.--(BUSINESS WIRE)--$AGEN #Botensilimab--Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, today announced new findings from a long-term survivor analysis of its Phase 1b C-800-01 trial evaluating botensilimab (BOT), a multifunctional, Fc-enhanced anti-CTLA-4 antibody, in combination with balstilimab (BAL), an anti-PD-1 antibody, in heavily pretreated patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases. The results were presented in a poster by Thomas U. Marron, MD, PhD, of the Tisch Cancer Center at Mount Sinai, at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting in Phoenix, Arizona.
For patients with MSS mCRC whose cancer has progressed despite multiple treatments, treatment options remain limited, even among patients without active liver metastases. Historical studies of available later-line treatment regimens have reported median overall survival of approximately 10–14 months in relevant populations.1,2 Because survival beyond 18 months remains uncommon in this setting, the analysis defined long-term survivors as patients who lived at least 18 months after starting BOT+BAL.
The new SITC analysis builds on previously reported results from the full 123-patient cohort, which demonstrated median overall survival of 21.2 months and a 33% estimated three-year survival rate, as presented at ESMO GI 2026 and published in Clinical Cancer Research. The current post-hoc analysis takes a closer look at the patients who achieved long-term survival, examining their clinical characteristics, the durability of their responses and factors that may help explain their outcomes.
The analysis found that 51% (63/123) of patients survived at least 18 months after starting BOT+BAL, including patients who had received prior immunotherapy and undergone several rounds of different treatment. Among the 63 long-term survivors, median overall survival had not been reached and an estimated 59% were alive at three years.
“For patients with metastatic MSS colorectal cancer without active liver metastases who have exhausted multiple therapies, living another year and a half or more is rare,” said Thomas U. Marron, MD, PhD, of the Tisch Cancer Center at Mount Sinai and presenting author of the study. “What is particularly interesting is that the long-term survivors did not fit a single favorable clinical profile. Durable benefit was seen even in patients previously treated with immunotherapy, and a subset remains alive without any further cancer treatment. These findings suggest the potential to meaningfully change the course of disease and provide a compelling rationale for evaluating this approach earlier in treatment.”
Clinical Characteristics and Outcomes of Long-Term Survivors
This post hoc analysis compared patients who survived at least 18 months after initiating BOT+BAL (n=63) with those who survived less than 18 months (n=60).
- Broad patient characteristics: The two groups were generally similar across the characteristics examined including performance status, previous immunotherapy treatment, metastatic disease characteristics and several prognostic biomarkers.
- Durable responses: Among long-term survivors, 35% (22/63) had a confirmed tumor response, including three complete responses in which tumors disappeared. Median duration of response was not reached, with responses lasting at least 37.4 months and 10 ongoing at the time of reporting. Patients in both the full cohort and long-term survivor group received a median of two BOT doses.
- Time off treatment: Approximately 24% (15/63), or one in four long-term survivors, were alive and off all anticancer treatment at time of last follow-up. Of these patients, 13 had achieved tumor responses with BOT+BAL.
- Prior treatment exposure: Long-term survivors were less likely to have received three or more prior lines of treatment, 56% (35/63) compared with 78% (47/60) of shorter-term survivors.
Safety Findings
No treatment-related deaths were observed. Immune-mediated adverse events occurred more frequently among long-term survivors than in the overall cohort. Immune-mediated diarrhea or colitis was the most frequently reported immune-mediated adverse event. Among long-term survivors who developed it, 97% (33/34) experienced resolution, with a median time to resolution of 13 days. Management included early corticosteroids and TNFα-directed therapy, when appropriate.
“The significance of these data extends beyond the survival milestone itself,” said Steven J. O’Day, MD, Chief Medical Officer of Agenus. “Deep responses and durable disease control in heavily pretreated, immunologically cold tumors reinforce the potential of BOT’s differentiated Fc-enhanced immune-priming approach. The association between fewer prior therapies and long-term survival strengthens the rationale for evaluating BOT+BAL earlier in the course of disease. This is central to our Phase 3 ROBBIN strategy, which is designed to evaluate a short course of BOT+BAL before surgery in high-risk MSS colon cancer, with the goal of reducing recurrence, de-escalating the need for chemotherapy and increasing the potential for cure.”
The full poster will be available at www.agenusbio.com/publications.
SITC 2026 Presentation Details
Title: Clinical Features of Long-Term Survivors Treated with Next-Generation Anti–CTLA-4 (Botensilimab) Plus Anti–PD-1 (Balstilimab) in Refractory Microsatellite-Stable Metastatic Colorectal Cancer
Presenter: Thomas U. Marron, MD, PhD; Tisch Cancer Center at Mount Sinai, New York, NY
Date: Saturday, November 7, 2026
Time: 10:00 a.m.–2:00 p.m. and 6:00–8:10 p.m. MST | 12:00–4:00 p.m. and 8:00–10:10 p.m. EST
Location: North Building, Lower Level, Exhibition Halls 4–5–6, Phoenix, Arizona
Poster Number: 472
BOT and BAL are investigational outside Armenia and are not approved by the U.S. Food and Drug Administration.
About the C-800-01 Study (NCT03860272)
C-800-01 (NCT03860272) is an ongoing, multicenter Phase 1b clinical trial evaluating botensilimab in combination with balstilimab across advanced solid tumors. The trial enrolled over 400 patients with refractory disease and included tumor types with limited or no responsiveness to prior checkpoint inhibitors. Endpoints included objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
The data presented at SITC 2026 are from the MSS mCRC cohort, which included 123 patients without active liver metastases who received BOT 1 or 2 mg/kg every six weeks with BAL 3 mg/kg every two weeks. The primary endpoint was safety and tolerability. The present analysis retrospectively defined long-term survivors as those living at least 18 months from treatment start. Data cutoff was December 13, 2025.
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.
Agenus’ Commitment to Patient Access
Agenus is committed to expanding patient access to BOT+BAL through regulatory approvals, clinical trials and authorized early-access pathways. Following the first marketing authorizations for Botvymo® (botensilimab) and Evamplix® (balstilimab) in Armenia for eligible adults with microsatellite stable (MSS) metastatic colorectal cancer without active liver metastases who have previously received available standard therapies, BOT+BAL remains investigational outside Armenia and is not approved by the U.S. Food and Drug Administration (FDA).
In France, the national Autorisation d’Accès Compassionnel (AAC) program provides fully reimbursed, hospital-based access to BOT+BAL for eligible patients with MSS metastatic colorectal cancer without active liver metastases, platinum-resistant or platinum-refractory ovarian cancer, and certain advanced soft-tissue sarcomas. In a growing number of other countries, BOT+BAL is available through physician-initiated named-patient programs under local regulations. BAP Pharma serves as Agenus’ global partner for the French AAC pathway and named-patient access programs.
Physicians seeking information about authorized access pathways can visit the Patient Access section of the Agenus website.
About Botensilimab (BOT)
Botensilimab (BOT) is a human multifunctional, Fc-enhanced 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. BOT augments immune responses across a wide range of tumor types by priming and activating T cells, reducing intratumoral regulatory T cells, activating myeloid cells and inducing durable memory responses.
Approximately 1,500 patients have been treated with BOT and balstilimab (BAL) in phase 1 and phase 2 clinical trials. The combination with Agenus’ investigational PD-1 antibody, BAL, has shown clinical responses across more than nine cancers. For more information about BOT 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.
References
1. Garcia-Carbonero R, et al. Efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer with and without liver metastasis: FRESCO-2 subgroup analysis. Poster 520P, ESMO 2024.
2. Cohen R, et al. Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis. Eur J Cancer. 2024;207:114160.
Contacts
Investors
917-362-1370 | investor@agenusbio.com
Media
781-674-4422 | communications@agenusbio.com
