On June 29, 2022 Agenus (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of therapeutics designed to activate the immune response to cancers and infections, reported expanded data from the Phase 1b study of botensilimab (Fc-enhanced anti-CTLA-4) and balstilimab (anti-PD-1) in patients with microsatellite stable colorectal cancer (MSS CRC) (Press release, Agenus, JUN 29, 2022, View Source [SID1234616374]). The data demonstrate that the combination offers strong durability and superior efficacy than what has been reported in separate trials for standard of care and other investigational therapies in 2L+ MSS CRC.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These data reinforce the strong therapeutic potential of botensilimab, when used in combination with balstilimab, in cold tumors such as MSS CRC," said Steven O’Day, MD, Chief Medical Officer at Agenus. "Thus far, botensilimab has demonstrated activity in nine cold and treatment-resistant cancers, and we plan to initiate a robust, global Phase 2 program, including in MSS CRC, later this year."

Study Highlights

A total of 41 evaluable patients with metastatic MSS CRC received either 1 or 2 mg/kg botensilimab Q6W, and 3 mg/kg balstilimab Q2W. Patients were heavily pre-treated, with a median of 4 prior lines of therapy, and 34% had received prior immunotherapy. The botensilimab/balstilimab combination produced superior responses and strong durability, relative to what has been reported in separate trials for standard of care and other combinations currently in development.

Objective responses:

24% overall response rate
73% disease control rate (partial response + stable disease)
50% objective responses with greater than 50% tumor reduction
Durability:

80% objective responses ongoing at data cut-off
30% objective responses exceeding 1 year
Patient Sub-Populations:

Objective responses in 5 patients with RAS mutations for a 24% overall response rate and 81% disease control rate in this population; other PD-1 combinations in separate trials have reported only rare responses in this population (≤1% response rate)
Responses observed in patients with metastases historically resistant to immunotherapy, including patients with malignant pleural effusions, soft tissue, peritoneal, retroperitoneal, and bone metastases
Tolerability:

Botensilimab was well tolerated, with no grade 4/5 treatment-related adverse events
Rates of gastrointestinal and skin toxicities were comparable to those reported with first-generation CTLA-4 inhibitors
"Colorectal cancer is the second leading cause of cancer-related death worldwide, with roughly 95% classified as microsatellite stable and historically unresponsive to immunotherapy. Treatment resistant MSS CRC patients lack effective options, with standard of care offering only a 1-2% response rate and a median expected survival ranging from 6 to 7 months," said Anthony El-Khoueiry, MD, Phase I Program Director at the USC Norris Comprehensive Cancer Center, Keck Medicine of USC. "The combination of robust response rate, durability, and tolerability demonstrated by botensilimab and balstilimab supports further development of the combination in MSS CRC, as well as more broadly, in other cold and treatment-resistant tumors."

Presentation Details

The data were presented today at 7:05 AM EDT in a late-breaking oral presentation at the ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer in Barcelona, Spain.

Abstract Title: Botensilimab, a Novel Innate/Adaptive Immune Activator, Plus Balstilimab (Anti-PD-1) for Metastatic Heavily Pretreated Microsatellite Stable Colorectal Cancer

Abstract Number: LBA-09

Presenting Author: Dr. Anthony El-Khoueiry, M.D., Associate Director of Clinical Research at the USC Norris Comprehensive Cancer Center, Keck School of Medicine

Investor Webcast

The Company will host an investor webcast today at 10:00 AM EDT to review these data. Participants may register here, or on the Investors section of the Agenus website at investor.agenusbio.com. The webcast will include presentations by the below speakers and will be followed by a Q&A session:

Steven O’Day, M.D., Agenus’ Chief Medical Officer
Dr. Anthony El-Khoueiry, M.D., Associate Director of Clinical Research at the USC Norris Comprehensive Cancer Center, Keck School of Medicine
Dr. Manuel Hidalgo, Chief of the Division of Hematology and Medical Oncology at Weill Cornell Medicine/NewYork-Presbyterian Hospital, and
Dr. Heinz-Josef Lenz, M.D., Professor of Medicine and J. Terrence Lanni Chair in Gastrointestinal Cancer Research, Keck School of Medicine
Following the webcast, an archived version will be available on the Agenus website.