LEXINGTON, Mass.–Agenus reported that more than half of patients with heavily pretreated metastatic colorectal cancer survived at least 18 months after receiving its experimental combination immunotherapy, according to a new analysis of Phase 1b clinical trial data being presented at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting in Phoenix.
The findings involved 123 patients with microsatellite-stable (MSS) metastatic colorectal cancer who had previously received multiple treatments and had no active liver metastases. Patients received a combination of botensilimab (BOT), an investigational anti-CTLA-4 antibody, and balstilimab (BAL), an anti-PD-1 antibody.
Researchers found that 51% of patients, or 63 of 123, survived at least 18 months after beginning treatment. Among those classified as long-term survivors, an estimated 59% were alive three years after treatment began.
The results are part of a retrospective analysis of the ongoing C-800-01 Phase 1b trial, which is investigating the combination across several advanced solid tumors.
MSS colorectal cancer has historically been difficult to treat with immune checkpoint inhibitors because these tumors generally generate weaker immune responses than microsatellite instability-high cancers.
Patients whose disease has progressed after multiple treatment regimens have limited therapeutic options. According to Agenus, historical studies involving comparable later-line treatments have reported median overall survival of approximately 10 to 14 months.
Previous findings from the full 123-patient cohort showed a median overall survival of 21.2 months and an estimated three-year survival rate of 33%.
The latest analysis examined the characteristics of patients who lived at least 18 months, the durability of their responses and potential factors associated with longer survival.
“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.”
Among the 63 long-term survivors, 22 patients, or 35%, experienced a confirmed tumor response, including three complete responses in which detectable tumors disappeared.
The median duration of response had not been reached at the time of analysis, with some responses lasting at least 37.4 months. Ten patients continued to experience responses when the data were evaluated.
Approximately 24% of long-term survivors, or 15 patients, were alive and no longer receiving any anticancer treatment at their most recent follow-up. Of those patients, 13 had previously achieved a tumor response to the combination therapy.
Researchers also examined whether baseline characteristics could help distinguish patients who experienced longer survival from those who did not.
The two groups were generally similar in performance status, prior exposure to immunotherapy, characteristics of metastatic disease and several biological markers associated with prognosis.
However, patients who survived at least 18 months were less likely to have received three or more previous treatment regimens.
Among long-term survivors, 56% had undergone at least three prior lines of therapy, compared with 78% of patients who survived less than 18 months.
The finding suggests that patients treated earlier in the course of their disease may have a greater likelihood of achieving prolonged survival, although the retrospective analysis cannot establish whether treatment timing caused the difference.
The study also examined the safety of the combination treatment.
No treatment-related deaths were reported. Immune-mediated adverse events were more common among long-term survivors than in the overall study population.
Diarrhea and colitis were the most frequently reported immune-related complications.
Among long-term survivors who developed immune-mediated diarrhea or colitis, 97%, or 33 of 34 patients, experienced resolution of the condition, with a median recovery time of 13 days.
Treatment of these complications included early use of corticosteroids and therapies targeting tumor necrosis factor-alpha when clinically appropriate.
Steven J. O’Day, MD, Chief Medical Officer of Agenus, said the findings provide additional support for investigating the combination in earlier stages of colorectal cancer.
“The significance of these data extends beyond the survival milestone itself,” O’Day said. “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.”
Botensilimab is designed to enhance immune activation through its effects on CTLA-4, a protein involved in regulating immune responses. Balstilimab targets PD-1, another immune checkpoint that can prevent immune cells from effectively attacking cancer.
By combining the two approaches, Agenus is investigating whether the treatment can generate stronger immune responses against tumors that have historically shown limited sensitivity to checkpoint inhibitors.
The company is advancing the combination into its Phase 3 ROBBIN development program, which is designed to evaluate treatment before surgery in patients with high-risk MSS colon cancer.
The study will investigate whether administering a short course of immunotherapy before surgery can reduce cancer recurrence and potentially decrease the need for subsequent chemotherapy.
The Phase 1b C-800-01 trial enrolled more than 400 patients with advanced cancers that had progressed despite previous treatments. The colorectal cancer analysis focused on 123 patients without active liver metastases.
The analysis used a data cutoff of December 13, 2025, and defined long-term survival as living at least 18 months after initiating treatment.
Because the findings come from a retrospective analysis of an early-stage clinical trial without a randomized control group, they do not establish that the experimental treatment improves survival compared with existing therapies. Larger controlled trials will be needed to confirm its clinical benefits and safety.
The findings are scheduled for presentation November 7 at the SITC 2026 Annual Meeting in Phoenix.
Botensilimab and balstilimab remain investigational in the United States and have not received approval from the U.S. Food and Drug Administration. Agenus said the treatments have regulatory authorization in Armenia.
