Agenus Reports Long-Term Survival Benefits with Botensilimab and Balstilimab Combination in MSS Metastatic Colorectal Cancer at SITC 2026
Agenus Inc., a biotechnology company focused on developing innovative immuno-oncology treatments, has announced encouraging long-term survival findings from an analysis of its Phase 1b C-800-01 clinical trial evaluating the combination of botensilimab (BOT) and balstilimab (BAL) in heavily pretreated patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases. The findings were presented at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting in Phoenix, Arizona, highlighting the potential of the investigational immunotherapy combination to provide durable clinical benefits in a patient population with limited treatment options.
The analysis focused on patients who achieved long-term survival following treatment with botensilimab and balstilimab, examining their clinical characteristics, treatment responses, survival outcomes, and safety profiles. The findings provide additional insight into the potential of the combination to improve outcomes for patients with advanced MSS colorectal cancer, particularly those whose disease has progressed following multiple previous therapies.
The poster presentation was delivered by Thomas U. Marron, MD, PhD, of the Tisch Cancer Center at Mount Sinai. The research examined long-term outcomes among patients enrolled in the Phase 1b C-800-01 trial and evaluated factors associated with survival beyond 18 months after initiating treatment.
Metastatic MSS colorectal cancer represents a significant therapeutic challenge because these tumors generally demonstrate limited responsiveness to conventional immune checkpoint inhibitor treatments. Patients whose disease progresses after multiple lines of therapy frequently have few effective treatment alternatives. The need for innovative therapeutic strategies remains substantial, particularly for patients without active liver metastases who have exhausted available treatment options.
Historical studies evaluating later-line treatment approaches in relevant patient populations have reported median overall survival ranging from approximately 10 to 14 months. Survival beyond 18 months remains relatively uncommon in this setting. Based on this clinical context, the investigators defined long-term survivors in the current analysis as patients who remained alive for at least 18 months after beginning treatment with BOT+BAL.
The latest findings demonstrate that 51% of patients enrolled in the study survived for at least 18 months following treatment initiation. This included patients who had previously received immunotherapy and undergone several different treatment regimens. Among these long-term survivors, median overall survival had not been reached, while the estimated three-year survival rate was 59%.
These results provide additional evidence supporting the continued clinical development of Agenus’ immunotherapy combination in advanced colorectal cancer and strengthen the rationale for investigating the approach in earlier stages of disease.
Long-Term Survival Analysis Builds on Previously Reported Clinical Results
The new analysis builds on previously reported findings from the complete 123-patient cohort of the Phase 1b C-800-01 clinical trial. Earlier results, presented at the European Society for Medical Oncology Gastrointestinal Cancers Congress (ESMO GI) 2026 and published in Clinical Cancer Research, demonstrated a median overall survival of 21.2 months and an estimated three-year survival rate of 33% across the full study population.
The current post-hoc analysis was designed to provide a more detailed understanding of the patients who experienced prolonged survival following treatment with botensilimab and balstilimab.
Investigators examined outcomes among patients who survived at least 18 months and compared their clinical characteristics with those of patients whose survival was shorter than 18 months. The analysis included 123 patients, divided into two groups: 63 long-term survivors and 60 patients who survived for less than 18 months.
The researchers evaluated several factors, including performance status, previous immunotherapy exposure, metastatic disease characteristics, prognostic biomarkers, tumor response rates, duration of response, and treatment history.
The results indicated that long-term survival was not restricted to patients with a single favorable clinical profile. Patients with different disease characteristics and treatment histories experienced prolonged survival, including individuals who had previously received immunotherapy.
Thomas U. Marron, MD, PhD, of the Tisch Cancer Center at Mount Sinai and presenting author of the study, emphasized the importance of these findings for patients with advanced MSS metastatic colorectal cancer.
According to Dr. Marron, surviving another 18 months or longer is an uncommon outcome for patients whose disease has progressed despite multiple treatment approaches. He highlighted that the long-term survivors did not share one specific favorable clinical characteristic and that durable clinical benefits were observed even among some patients previously treated with immunotherapy.
He also noted that a subset of patients remained alive without receiving additional cancer treatment following their initial BOT+BAL therapy. These observations suggest that the combination may have the potential to alter the disease course in selected patients and provide a strong rationale for evaluating the treatment approach earlier in the disease progression pathway.
Clinical Characteristics and Outcomes of Long-Term Survivors
The post-hoc analysis compared the clinical outcomes of patients who survived at least 18 months following initiation of botensilimab and balstilimab with those who experienced shorter survival.
Of the 123 patients included in the analysis, 63 patients, representing 51% of the study population, achieved long-term survival. The remaining 60 patients survived for less than 18 months.
One important observation was that the two groups generally demonstrated similar characteristics across several clinical and disease-related parameters. These included performance status, previous exposure to immunotherapy, metastatic disease characteristics, and selected prognostic biomarkers.
The findings suggest that prolonged survival following BOT+BAL treatment was not necessarily limited to patients with a clearly identifiable favorable baseline profile.
Durable tumor responses
Among the 63 long-term survivors, 35% (22 patients) achieved a confirmed tumor response following treatment with BOT+BAL. This included three patients who achieved complete responses, indicating that their tumors were no longer detectable according to the relevant response assessment criteria.
The duration of response was also encouraging. Median duration of response had not been reached at the time of analysis, with responses continuing for at least 37.4 months. Ten responses remained ongoing when the findings were reported.
These results highlight the possibility of prolonged tumor control in patients with advanced MSS colorectal cancer treated with the investigational combination.
Another notable finding was that patients in both the overall study population and the long-term survivor group received a median of two doses of botensilimab. This observation indicates that the prolonged clinical benefits reported in some patients occurred despite relatively limited exposure to the investigational anti-CTLA-4 antibody.
Patients remaining alive without additional treatment
The analysis also identified a group of long-term survivors who remained alive without receiving further anticancer treatment.
Approximately 24% of long-term survivors, representing 15 of the 63 patients, were alive and off all anticancer therapy at the time of their last follow-up.
Of these 15 patients, 13 had previously achieved tumor responses following treatment with BOT+BAL.
Remaining alive without additional anticancer treatment is an important clinical observation in metastatic colorectal cancer, particularly among patients whose disease has progressed after multiple treatment regimens.
This finding suggests that the combination may provide sustained disease control in a subset of patients, potentially reducing the need for immediate additional systemic treatment.
However, further follow-up and larger clinical studies will be necessary to determine the durability of these outcomes and identify the patients most likely to experience prolonged treatment-free survival.
Impact of previous treatment exposure
The researchers also examined the relationship between previous treatment exposure and long-term survival.
The analysis found that long-term survivors were less likely to have received three or more previous lines of treatment compared with patients who survived for less than 18 months.
Approximately 56% of long-term survivors, or 35 of 63 patients, had received at least three prior lines of therapy. In comparison, 78% of patients in the shorter-survival group, representing 47 of 60 individuals, had received three or more previous treatment lines.
This difference suggests that the number of previous treatment regimens may influence the likelihood of achieving prolonged survival following BOT+BAL therapy.
The observation also provides a potential rationale for evaluating the combination earlier in the treatment course, before patients have experienced extensive exposure to multiple systemic therapies.
Safety Profile and Management of Immune-Mediated Adverse Events
In addition to evaluating long-term efficacy, the analysis examined the safety profile of botensilimab and balstilimab in the Phase 1b C-800-01 trial.
No treatment-related deaths were observed in the study.
Immune-mediated adverse events were reported more frequently among long-term survivors than in the overall study population. Immune-mediated diarrhea or colitis was the most frequently reported immune-related adverse event.
Among long-term survivors who developed immune-mediated diarrhea or colitis, 97%, corresponding to 33 of 34 patients, experienced resolution of the condition.
The median time to resolution was 13 days.
The management of these events included early administration of corticosteroids and the use of tumor necrosis factor-alpha (TNFα)-directed therapies when clinically appropriate.
These findings provide additional information regarding the management of immune-related toxicities associated with the treatment combination.
Immune-mediated adverse events are recognized risks associated with immune checkpoint inhibitor therapies, particularly treatments targeting CTLA-4 and PD-1 pathways. Appropriate monitoring, timely recognition, and effective management are therefore important components of clinical treatment.
The resolution of most reported cases among long-term survivors demonstrates the importance of established management strategies in addressing these complications.
Nevertheless, continued safety evaluation will be necessary as the combination advances into larger and potentially earlier-stage clinical studies.
Agenus Highlights the Potential of Botensilimab’s Immune-Priming Approach
Steven J. O’Day, MD, Chief Medical Officer of Agenus, highlighted the broader significance of the long-term survival findings and their potential implications for immunotherapy development in MSS colorectal cancer.
According to Dr. O’Day, the significance of the analysis extends beyond the achievement of an 18-month survival milestone. The observation of deep tumor responses and durable disease control in heavily pretreated patients with immunologically cold tumors provides further support for the potential of botensilimab’s differentiated Fc-enhanced immune-priming mechanism.
He also emphasized the association between fewer previous treatment lines and long-term survival, noting that this finding strengthens the rationale for investigating BOT+BAL earlier in the disease course.
The company’s research strategy is focused on understanding how botensilimab can potentially improve immune recognition and activity against tumors that have historically demonstrated limited responsiveness to immunotherapy.
MSS colorectal cancer is generally considered an immunologically cold tumor type, meaning that it often has limited immune-cell infiltration and an unfavorable tumor microenvironment for effective immune-mediated tumor destruction.
Conventional immune checkpoint inhibitors have demonstrated limited clinical activity in many patients with MSS metastatic colorectal cancer. Therefore, approaches capable of stimulating broader immune responses and modifying the tumor microenvironment could offer an important therapeutic opportunity.
Botensilimab and Balstilimab: A Differentiated Immunotherapy Combination
Botensilimab is an investigational multifunctional, Fc-enhanced anti-CTLA-4 antibody developed by Agenus for the treatment of cancer.
CTLA-4 is an immune checkpoint protein that plays an important role in regulating T-cell activation. By targeting this pathway, botensilimab is designed to enhance immune-cell activation and support antitumor immune responses.
The antibody incorporates an Fc-enhanced design intended to strengthen interactions with immune cells and potentially support additional immune-mediated mechanisms beyond conventional CTLA-4 blockade.
Balstilimab is an investigational anti-PD-1 antibody designed to block the programmed cell death protein 1 (PD-1) immune checkpoint pathway.
PD-1 is expressed on immune cells and can suppress their activity when it interacts with its corresponding ligands in the tumor microenvironment. Blocking this pathway may help restore the ability of T cells to recognize and attack cancer cells.
The combination of botensilimab and balstilimab is intended to target complementary immune checkpoint mechanisms.
By combining CTLA-4 inhibition with PD-1 blockade, Agenus aims to stimulate antitumor immune activity through multiple pathways. The approach is particularly relevant to tumors such as MSS colorectal cancer, where conventional checkpoint inhibition has historically produced limited responses.
The clinical findings from the C-800-01 study provide encouraging evidence supporting further evaluation of this combination.
Phase 3 ROBBIN Strategy to Evaluate Treatment Earlier in Colon Cancer
Agenus is also advancing its immunotherapy development strategy through the Phase 3 ROBBIN program, which is designed to evaluate botensilimab and balstilimab in patients with high-risk MSS colon cancer before surgery.
The company’s strategy involves investigating a short course of BOT+BAL as a preoperative treatment approach, with the objective of improving disease control before patients undergo surgical intervention.
The program is intended to evaluate whether this immunotherapy combination can reduce the risk of cancer recurrence, potentially decrease the need for chemotherapy, and improve the possibility of achieving a cure in patients with high-risk disease.
This development strategy reflects the company’s interest in moving its immunotherapy approach into earlier treatment settings rather than limiting its investigation to patients with advanced disease who have exhausted multiple therapeutic options.
The long-term survivor analysis from the C-800-01 trial provides additional support for this direction. In particular, the association between fewer previous treatment lines and longer survival highlights the importance of investigating whether earlier intervention could improve clinical outcomes.
Although the metastatic disease findings and the ROBBIN clinical strategy involve different treatment settings, the results contribute to the broader scientific rationale for evaluating botensilimab-based immunotherapy across stages of colorectal cancer.
Advancing Immunotherapy Options for MSS Metastatic Colorectal Cancer
The latest SITC 2026 findings represent an important clinical development milestone for Agenus as it continues evaluating botensilimab and balstilimab in patients with difficult-to-treat colorectal cancer.
The analysis demonstrated that 51% of patients in the 123-patient Phase 1b C-800-01 cohort survived for at least 18 months following treatment initiation. Among these long-term survivors, median overall survival had not been reached, and the estimated three-year survival rate was 59%.
The observation of confirmed tumor responses in 35% of long-term survivors, including three complete responses, further highlights the potential for durable clinical activity. Additionally, approximately one-quarter of long-term survivors remained alive without receiving further anticancer treatment at their last follow-up.
The safety analysis showed no treatment-related deaths, while most reported cases of immune-mediated diarrhea or colitis among long-term survivors resolved following appropriate management.
Together, these findings strengthen the rationale for further clinical investigation of the combination, particularly in earlier treatment settings where patients may have greater opportunities to benefit from immune-based approaches.
Through its ongoing clinical development programs, including the Phase 3 ROBBIN strategy, Agenus aims to determine whether its differentiated immunotherapy platform can improve outcomes for patients with MSS colorectal cancer, a population with significant unmet medical needs.
The company continues to explore the potential of botensilimab and balstilimab to deliver meaningful and durable clinical benefits across colorectal cancer treatment settings.
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.