Breakthrough Data on Botensilimab/Balstilimab in MSS CRC Presented at the 2024 ASCO Annual Meeting
Agenus has announced new data from a Phase 1b trial involving botensilimab and balstilimab (BOT/BAL) in relapsed/refractory microsatellite stable colorectal cancer (r/r MSS CRC). These findings, to be presented at the 2024 ASCO Annual Meeting, highlight the efficacy of BOT/BAL in metastatic sites beyond the lungs and lymph nodes, including the peritoneum, soft tissue, and brain. The trial involved 77 heavily pre-treated patients, showing overall response rates (ORR) between 18-33% and disease control rates (DCR) from 67-82%. The overall survival (OS) ranged from 20.7 months to not reached (NR). No new safety signals were reported.
- BOT/BAL shows efficacy in historically unresponsive metastatic sites like peritoneum, soft tissue, and brain.
- Overall response rates (ORR) ranged from 18-33% across various NLM sites.
- Disease control rates (DCR) were between 67-82%.
- Overall survival (OS) ranged from 20.7 months to not reached (NR).
- No new safety signals were observed in the trial.
- Patients had a high median of four prior lines of therapy, indicating a heavily pre-treated group.
- data on the long-term durability of BOT/BAL benefits beyond the trial period.
- Unclear how results will translate to a broader patient population beyond the trial group.
Microsatellite stable colorectal cancer (MSS CRC) is particularly challenging to treat due to its resistance to conventional immunotherapies. The latest data from Agenus on the BOT/BAL combination trial offers some promising signs for a subset of these patients.
The most striking aspect is the demonstrated activity in metastatic sites that have traditionally been unresponsive, including the peritoneum, soft tissue and brain. An overall response rate (ORR) between 18-33% and a disease control rate (DCR) ranging from 67-82% show potential efficacy, especially considering these patients have been heavily pre-treated.
Moreover, the consistent overall survival (OS) data, with some parameters not even reached, suggests a potential for prolonged benefits. Importantly, the absence of new safety signals is crucial, as it indicates that patients are not being exposed to unexpected risks.
These findings could mark a significant step forward in the treatment of MSS CRC, a notoriously stubborn cancer, by potentially extending the benefits of immunotherapy to a broader patient population.
The presentation of the Phase 1b trial data on BOT/BAL at the ASCO Annual Meeting underscores the potential of this combination therapy in addressing unmet needs in relapsed/refractory microsatellite stable colorectal cancer (r/r MSS CRC).
Analyzing the clinical findings, the response and control rates across various non-liver metastatic sites are noteworthy, especially in light of the patient demographics. These patients had a median of four prior lines of therapy, indicating a highly pre-treated group. The reported overall survival (OS) ranging from 20.7 months to not reached (NR) supports the hypothesis of durable benefits.
The fact that the combination therapy showed activity beyond traditional sites, like the lungs and lymph nodes and into more refractory areas like the brain, peritoneum and soft tissues, is particularly compelling. This expands the horizons of immunotherapy applications in colorectal cancer.
New analysis highlights BOT/BAL activity across challenging metastatic disease sites
“The findings observed in this analysis are notable in that they are seen within challenging and historically unresponsive metastatic sites of disease,” said Dr. Steven O'Day, Chief Medical Officer at Agenus. “Seeing broad activity beyond the lungs and lymph nodes is rare for immunotherapy in MSS mCRC, making BOT/BAL stand out from other treatments. We are committed to advancing BOT/BAL for those living with cancer, with the intent to provide durable long-term benefits.”
Patient Demographics
- A total of 77 patients with NLM MSS mCRC were treated with 1 or 2 mg/kg BOT every 6 weeks plus 3 mg/kg BAL every 2 weeks.
-
Patients were heavily pre-treated, with a median of four prior lines of therapy, including
21% who received prior PD-(L)1/CTLA-4 therapy. -
Location of NLM sites: 62 patients (
81% ) had lung involvement, 33 patients (43% ) had peritoneal involvement, 32 (42% ) patients had lymph node involvement, 15 patients (19% ) had soft tissue involvement, and 18 patients (23% ) had other sites including the bone and brain.
Clinical Findings
-
Across different NLM sites, overall response rates (ORR) ranged from 18
-33% and disease control rates (DCR) ranged from 67-82% . Overall survival (OS) remained consistent and ranged from 20.7 months to not reached (NR). - No new safety signals were observed.
Presentation Details:
Abstract Title: Botensilimab plus balstilimab in microsatellite stable metastatic colorectal cancer: Assessing efficacy in non-liver metastatic sites.
Abstract Number: 3556
Presenting Author: Marwan Fakih, MD, Division Head, GI Medical Oncology, City of Hope Comprehensive Cancer Center
Session: Poster Session – Gastrointestinal Cancer – Colorectal and Anal
Session Date and Time: June 1, 2024, at 1:30 p.m. – 4:30 p.m. CT
About Botensilimab
Botensilimab is a human Fc enhanced CTLA-4 blocking 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 900 patients have been treated with botensilimab 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 with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.
About Agenus
Agenus is a leading immuno-oncology company targeting cancer and infectious diseases with a comprehensive pipeline of immunological agents. The company’s mission is 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 (through SaponiQx). Agenus is headquartered in
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 a 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 2022, 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.
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FAQ
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