Agenus Unveils New and Updated Botensilimab Data in Colorectal, Pancreatic, Lung, Melanoma, and Sarcoma
- Agenus plans to file a Biologics License Application (BLA) for its BOT/BAL combination therapy in midyear 2024 for the treatment of metastatic colorectal cancer (CRC)
- Improved responses and durability were observed in refractory MSS CRC patients
- Promising clinical outcomes were seen in neoadjuvant MSS CRC patients
- Compelling activity was shown in relapsed/refractory advanced pancreatic cancer, melanoma, NSCLC, and sarcoma
- None.
Potential Accelerated Filings for Advanced Pancreatic Cancer and Melanoma in 2025
Opportunity to Expand into Early-Stage Cancers Supported by Compelling Neoadjuvant CRC Data
Live Webcast Today at 1:00 p.m. EDT
“These new and updated data underscore BOT’s broad effectiveness across several advanced solid tumors, demonstrating its potential beyond first-generation immunotherapies and current treatments,” said Dr. Steven O’Day, Chief Medical Officer. “BOT’s versatility, alone, in combination with BAL, or in combination with other standard of care therapies, in early and late-stage solid tumors, positions Agenus to transform cancer care, offering immense promise to patients.”
Key highlights across solid tumors include:
Extended Follow-up and Additional Data in Refractory MSS CRC Demonstrate Improved Responses and Durability
In 70 efficacy evaluable patients with MSS CRC and no active liver metastases:
-
Confirmed (RECIST 1.1) overall response rate (ORR) of
24% was observed, compared to2.8% reported with standard of care (SOC) in 2/3L+ MSS CRC patients with no active liver metastases1. -
12-month overall survival (OS) of
74% and median OS (mOS) not yet reached. Median follow up now 12.3 months.
Subsequent data from expanded cohorts and early signals from a 230 patient Phase 2 trial is consistent with the earlier cohort of 70 patients. Based on the totality of the evidence from the Phase 1 and Phase 2 trials, Agenus plans to submit its Biologics License Application (BLA) to the
Robust Clinical Outcomes in Neoadjuvant MSS CRC Underscore BOT/BAL’s Potential in Earlier-Stage Patients*
- All patients treated with one dose of BOT and two doses of BAL.
- After dosing, observations of responses were made within approximately four-weeks prior to surgery.
-
100% (3/3) of patients with MSI-H CRC had major pathological responses (>90% ). -
67% (6/9) patients with MSS CRC had pathological responses of >50% , which includes two complete pathological responses. - These findings offer an alternative path to minimize or eliminate radical rectal surgery and its associated morbidities such as colostomy dependance and sexual dysfunction, and potentially avoid the need for systemic chemotherapy.
- Agenus plans to prioritize neoadjuvant development and is evaluating study design for further regulatory activity.
Compelling Activity from Dose-escalation Portion of Phase 2 BOT/Chemotherapy Combination in Advanced (2L) Pancreatic Cancer
-
In FOLFIRINOX relapsed/refractory (2L) pancreatic cancer,
80% of evaluable patients (n=5; 150mg BOT+gem-Abraxane) experienced sustained tumor marker reductions. All patients had liver metastases. -
Two partial responses were at 16 weeks with target lesion reduction of -
47% (confirmed) and -37% (pending confirmation), and both responses remain ongoing. -
Two other patients showed stable disease with tumor reduction of -
20% and -13% at 8 weeks and remain on study awaiting 16-week scans. - A Phase 2 randomized study is enrolling.
Monotherapy Activity in CTLA-4 Relapsed/Refractory Advanced (2L+) Melanoma
-
Phase 1 expansion cohort in relapsed/refractory (2L+) melanoma (n=10) showed a
30% ORR and60% disease control rate; 8/10 patients had multiple prior lines including anti-PD-1/CTLA-4 and failed BRAF targeted therapy (n=5). - An accelerated Phase 2 trial in patients who have failed anti-CTLA-4 and PD-1 is underway; BOT monotherapy cohort is fully enrolled and BOT/BAL combination is enrolling.
Compelling Responses in Refractory NSCLC
-
Patients treated with PD(L)-1 refractory NSCLC were treated with BOT/BAL combination and showed a
56% ORR and89% disease control rate (n=9). -
Importantly, in patients with EGFR mutations refractory to SOC responded to the BOT/BAL combo, with one patient experiencing an -
90% tumor reduction** at 12 weeks and the second having a -42% tumor reduction at 6 weeks and is pending confirmation. - Expansion cohorts are underway with anticipated enrollment of 100 patients by 1Q 2024.
- Additional data from this study will be reported in midyear 2024.
Broad and Durable Activity in Advanced Sarcomas
Updated data was presented at ESMO 2023 from the Phase 1b study in 41 efficacy evaluable heavily pretreated advanced sarcoma patients, demonstrating durability with extended follow-up and additional activity in difficult-to-treat subtypes such as leiomyosarcoma.
-
BOT/BAL combination demonstrated 6-month progression-free survival of
40% , ORR of20% , and median response duration of 19.4 months (iRECIST). -
Differential responses observed by dose level, with
29% ORR at 2 mg/kg BOT compared to15% at 1 mg/kg BOT.
Webcast Details
A live webcast will be held today at 19:00 – 21:00 CEST (1:00 p.m. – 3:00 p.m. EDT). To register for the webcast, please click here.
References:
- Cohen et al. "Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis." ASCO Annual Meeting 2023, Abstract 3554
*Investigator Sponsored Trial
**Investigator reported, subject to change.
About Botensilimab
Botensilimab is an investigational multifunctional anti-CTLA-4 immune activator (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 750 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.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231022881056/en/
Investors
917-362-1370
investor@agenusbio.com
Media
781-674-4784
communications@agenusbio.com
Source: Agenus Inc.
FAQ
What is Agenus planning to do with its BOT/BAL combination therapy in midyear 2024?
What were the results of the therapy in refractory MSS CRC patients?
What were the clinical outcomes in neoadjuvant MSS CRC patients?
What other cancers did the therapy show activity in?
Where can I find more information about the findings?
