The colon and rectum are parts of the body’s digestive system and together form a long, muscular tube called the large intestine. The colon is the first 6 feet of the large intestine and the rectum is the last 8-10 inches. According to estimates from the American Cancer Society, more than 100,000 individuals will be diagnosed with colorectal cancer in the United States this year making colorectal cancer the third most common cancer among U.S. men and women.1
When detected early many colon cancers can be cured with surgery with or without systemic chemotherapy. When the cancer recurs following initial treatment or spreads beyond the colon it is referred to as advanced or metastatic cancer. Current therapies may control the cancer but are rarely curative and new treatments for advanced disease are needed.
The combination of Botensilimab plus Balstilimab immunotherapy appears promising according to recently published clinical trial results.
Single agent immunotherapy with anti–PD-1 or PDL-1 agents are inactive in advanced colon cancer. Responses are also very rare with first generation CTLA–4-based immunotherapy combinations and immunotherapy in CRC thus far. Immunotherapy is largely limited to individuals with microsatellite “high” disease.
The majority of patients with CRC have microsatellite stable (MSS) disease and this does not respond to immunotherapy. New research however suggests that treatment with a novel immunotherapy combination of botensilimab plus balstilimab has significant anti-cancer activity. Results from an early phase clinical trial evaluating this approach were presented at the ESMO World Congress on Gastrointestinal Cancer in Barcelona, Spain.
About Botensilimab
Botensilimab is an Fc-enhanced CTLA-4 antibody. In addition to blocking the interaction of CTLA-4 with its ligands, the enhanced Fc portion grants it several unique properties, such as increased frequency of dendritic cell concentration, a boost in T-cell formation, T-cell memory formation, T-cell priming, and enhanced T-reg depletion. Basiliximab is an IgG4, anti–PD-1 antibody with a similar profile to other anti–PD-1 agents (Keytruda, Opdivo etc).
Researchers evaluated the combination of botensilimab plus balstilimab in 41 patients with Microsatellite stable advanced colon cancer who were heavily pretreated. More than 50% of patients had received 4 or more previous lines of chemotherapy treatment.
The objective response rate was reported to be 24% with 10 patients having a partial response and 20 having stable disease for an overall disease control rate of 73%. Eight of the 10 patients responses are still ongoing, and 3 have gone beyond 1 year. Only 1 responder was reported to have high PDL-1 expression, and all responders had a TMB of 10 or less. Data suggested a higher response rate in patients without liver metastasis. The overall response rate was actually 42% and the disease control was 96% in patients without liver metastasis.
The combination of botensilimab (AGEN1181) and balstilimab (AGEN2034) produced a 19% response rate and provided overall survival benefits in patients with microsatellite stable metastatic colorectal cancer that is resistant to chemotherapy and/or immunotherapy, according to data from the phase 1 C-800-01 trial (NCT03860272). The doublet resulted in a median survival duration of 20.9 months in patients without active liver metastases (n = 69). In those with active liver metastases. The 12-month survival rate in refractory patients was 62%, for those without active liver metastases, the survival rate at 1 year was 74%.2
Overall, 76% of patients had treatment related side effects, but the majority of these were mild. The most common severe side effect was diarrhea colitis which was manageable with steroids and infliximab.
In summary, this novel immunotherapy combination is quite promising. A randomized phase 2 study in MSS colorectal cancer patients will launch later this year.
Connect With Others for Support and information
Cancer Connect was the first social network created for people with cancer. Founded by oncologists to support colon cancer patients and their caregivers, over 40 million individuals have accessed Cancer Connect programs since 1997. Cancer Connect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating cancer from others. Share your experience, ask a question, or start a conversation by posting on Cancer Connect.
Reference
- Bullock A, Grossman J, Fakih M, et al. Botensilimab, a novel innate/adaptive immune activator, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 29-July 2, 2022. Barcelona, Spain. Abstract LBA O-9.
- Bullock AJ, Fakih MG, Gordon MS, et al. Results from an expanded phase 1 trial of botensilimab, a multifunctional anti-CTLA-4, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer. Ann Oncol. 2023;34(suppl 1):S178-S179. doi:10.1016/j.annonc.2023.04.014
