On November 14, 2022 Agenus (Nasdaq: AGEN), an immuno-oncology company with a broad pipeline targeting cancer and infectious disease, reported expanded data from the Company’s Phase 1 study of botensilimab (Fc-enhanced anti-CTLA-4) and balstilimab (anti-PD-1) in patients with treatment-resistant tumors, including MSS-CRC, ovarian, sarcoma and NSCLC (Press release, Agenus, NOV 14, 2022, View Source [SID1234624040]). The data presented represents four of the most mature data sets from the nine cancer types where responses have been observed to date. The data was presented at a plenary session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting and a company-hosted R&D event.

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"This expanded dataset demonstrates the tremendous potential of botensilimab and balstilimab to treat a wide range of immunotherapy-resistant tumors," said Steven O’Day, M.D., Chief Medical Officer of Agenus. "Importantly, the superior efficacy we observed in our MSS-CRC presentation at GI ESMO (Free ESMO Whitepaper) earlier this year has remained consistent across a larger dataset. Further, we are seeing a strong signal with higher response rates than has been reported with other immunotherapies in multiple tumor types, including anti-PD-(L)1 relapsed/refractory NSCLC. These data provide compelling support for our ongoing Phase 2 botensilimab development program and highlight the broad therapeutic potential of botensilimab across solid tumors."

Study Design and Highlights

Out of over 250 enrolled patients, data on 125 patients has matured to efficacy and safety evaluation. These include four primary expansion cohorts in MSS CRC, recurrent platinum refractory/resistant ovarian, sarcoma and PD-(L)1 relapsed/refractory NSCLC. Patients in these cohorts received either 1 or 2 mg/kg botensilimab every 6 weeks and 3 mg/kg balstilimab every 2 weeks, with imaging assessments every six weeks. Fixed dosing was also permitted whereby patients received botensilimab 150 mg every 6 weeks, and balstilimab 450 mg every 3 weeks. Trial enrollees were heavily pre-treated with the majority receiving at least 3 prior lines of therapy.

MSS-CRC:

59 evaluable patients
76% failed on ≥3 prior lines of therapy
34% did not respond to prior experimental I-O
22% overall response rate: 1 complete response (CR), 12 partial responses (PR)
Other PD-(L)1 + CTLA-4 combination regimens in comparable patient populations achieved only 1-5% response rates1,2
73% disease control rate
Median duration of response not reached
69% of responses are ongoing
31% of responses have already exceeded 1 year
Median Progression Free Survival (mPFS) of 4.1 months; 12 month Overall Survival (OS) of 60.4%; median Overall Survival (mOS) has not been reached
Other PD-(L)1 + CTLA-4 combination regimens in comparable patient populations achieved a 1.8 mPFS and 6.6 mOS
Ovarian:

19 evaluable patients
71% received ≥3 prior lines of therapy
26% overall response rate: 1 CR, 4 PRs
Other PD-(L)1 + CTLA-4 combination regimens in comparable patient populations achieved only 3-10% response rates3,4
63% disease control rate
Median duration of response not reached
Sarcoma:

12 evaluable patients
73% received ≥3 prior lines of therapy
42% overall response rate: 1 CR, 4 PRs
Other PD-(L)1 + CTLA-4 combination regimens in comparable patient populations achieved only 12-16% response rates5,6
50% response rate in angiosarcoma, including 3 of 4 patients with visceral angiosarcoma
Other PD-(L)1 + CTLA-4 combinations achieved only 20-25% response rates with no reported responses in 7 treated patients with visceral angiosarcoma6,7
67% disease control rate
Median duration of response not reached
60% of responses have already exceeded 1 year and are ongoing
Anti-PD-(L)1 Relapsed/Refractory NSCLC:

5 evaluable patients (including 1 evaluable patient dosed after the data cut-off)
60% overall response rate
Other PD-(L)1 + CTLA-4 combination regimens in comparable patient populations achieved only 6-13% response rates8,9
80% disease control rate
Median duration of response not reached
67% of responses are ongoing
Tolerability:

Botensilimab was well tolerated, with no new immune-mediated safety signals outside of those observed in the class. Rates of gastrointestinal and skin toxicities were comparable to those reported with first-generation CTLA-4 inhibitors, while other immune mediated toxicities were less frequent than expected, consistent with botensilimab’s design to reduce complement binding.

"There is an urgent need to develop new therapies for patients suffering with cold and refractory tumors as current standards of care typically offer only single-digit response rates, "said Breelyn Wilky, M.D., Principal Investigator and Director of Sarcoma Medical Oncology at the University of Colorado School of Medicine. "The robust and durable clinical responses demonstrated by botensilimab and balstilimab in this study across a wide spectrum of refractory tumor types, coupled with its well-tolerated safety profile, provide strong support for the further development of this combination in a broad range of patients."

Presentation Details:

Abstract Number: 778

Abstract Title: Botensilimab, a novel innate/adaptive immune activator, plus or minus balstilimab (anti-PD-1) in ‘cold’ and I-O refractory metastatic solid tumors

Presenting Author: Breelyn A. Wilky, M.D., Director of Sarcoma Medical Oncology, Deputy Associate Director for Clinical Research University of Colorado School of Medicine

The data were presented on Saturday, November 12 at both the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) and "The Road Taken" R&D event hosted offsite by Agenus. An archived version of each presentation will be available on the Agenus website.