More details from a phase 1b study conducted by Agenus Inc. (Nasdaq:AGEN), a leader in developing novel immunological therapies for the treatment of various cancers, have been made available. The study involved the administration of balstilimab (BAL, anti-PD-1) and botensilimab (BOT, multifunctional immune activator) to patients with advanced sarcomas. The results were presented orally at the 2023 European Society for Medical Oncology (ESMO) Congress.
There is a significant unmet medical need in cases of resistant or relapsed sarcoma, where previous immunotherapies have shown minimal benefit and existing standard of care options are insufficient. Only a moderate response is now seen in patients with advanced soft tissue sarcoma to current therapies. The objective of the phase 1b trial, which involves the sarcoma cohort, is to evaluate the safety, efficacy, and dose optimisation .
“These findings support the exciting potential of BOT+BAL in a variety of cold, resistant solid tumours,” Chief Medical Officer Dr. Steven O’Day stated. Surprisingly, we saw a number of patients with immune-suppressive visceral angiosarcoma and other cold subtypes like leiomyosarcoma have long-lasting responses that lasted longer than a year. In order to optimise patient benefit, we plan to concentrate on important subsets and dosage techniques as we grow the trial.”
“As the research has progressed, BOT+BAL has shown good results with a 40% 6-month progression-free survival rate and a median response length of 19.4 months in a broader cohort of patients with sarcomas that are difficult to treat. In addition, we’re observing a dose-dependent benefit, with an objective response rate of 29% at 2 mg/kg,” stated Dr. Breelyn Wilky, MD, the study investigator and director of sarcoma medical oncology at the University of Colorado.
Study Plan and Principal Findings
41 evaluable patients in total were given 3 mg/kg BAL every two weeks and 1 or 2 mg/kg BOT every six weeks.
The majority of patients had subtypes of either leiomyosarcoma (39%) or angiosarcoma (29%)
With a median of three previous lines of therapy, including 16% who had previously received PD-(L)1 therapy, the patients were highly pre-treated.
The majority of patients had indicators that were linked to a subpar immunotherapy response:
Tumour mutation burden was minimal in 87% of cases (<10 mutations per megabase). PD-L1 was not detected by immunohistochemistry in 74% of the cases. Clinical Results Efficacy in all comers (n=41; iRECIST measurement) Six-month PFS of 40% 20% Return on Investment 29% ORR at the dosage level of BOT 2 mg/kg 15% ORR at the dosage level of 1 mg/kg 63% disease control rate (partial response plus stable disease plus best response) The response time on average was 19.4 months. All comers' safety (N=50) There have been no new safety signals revealed, and tumour type tolerability is constant. The majority of adverse effects were controllable and reversible. The most clinically important immune-mediated adverse event was diarrhoea or colitis. There were no documented instances of treatment-related grade 4 or 5 adverse effects or associated occurrences of irreversible events including hypophysitis, pneumonitis, hepatitis, or myocarditis. Presentation Information Title of Abstract: Safety and effectiveness of combined botensilimab (BOT) and balstilimab (BAL) in patients (pts) with metastatic sarcoma that is resistant (NCT03860272) Number of Abstract: 1919MO The author in question is Breelyn A. Wilky, MD, the University of Colorado Cancer Center's director of sarcoma medical oncology and deputy associate director for clinical research. Date and Time of Session: October 21, 2023; 10:15 a.m. to 11:45 a.m. CEST Time and Date of Presentation: October 21, 2023, 11:00 a.m. to 11:05 a.m. EST The presentation can be accessed at https://agenusbio.com/publications on the Agenus website. Citations Lancet Oncol. 2018;19; D'Angelo SP, et al. 2. J Clin Oncol. 2020;38(15)_suppl:11511-11511 Chen JL, et al. 3. J Immunother Cancer. 2021;9:e002990; Wagner MJ, et al. Regarding Botensilimab An experimental multifunctional anti-CTLA-4 immune activator called bensilimab is intended to enhance both innate and adaptive immune responses against tumours. Because of its unique architecture, immunotherapy benefits can now be extended to "cold" tumours, which typically do not react well to normal care or are resistant to both conventional PD-1/CTLA-4 therapies and other experimental therapies. By priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells, and eliciting long-term memory responses, betensilimab enhances immune responses against a variety of tumour types. In phase 1 and phase 2 clinical trials, botensilimab has been administered to about 600 individuals. Clinical responses have been observed with either benalimab alone or in conjunction with Agenus’ experimental anti-PD-1 drug, balstilimab, in nine metastatic, late-stage malignancies. Visit www.clinicaltrials.gov and enter the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316 to learn more about botensilimab trials. Agenus is a top immuno-oncology business that uses a broad pipeline of immunological medicines to treat infectious diseases and cancer. The company's goal is to increase the number of patients who can benefit from cancer immunotherapy by combining several strategies, such as adjuvants (via SaponiQx), adoptive cell therapies (through MiNK Therapeutics), and antibody therapeutics. The main office of Agenus is located in Lexington, MA. Go to www.agenusbio.com or @agenus_bio for additional information. Regular updates about information that might be of interest to investors will be made on our website and social media accounts. The following statements about Agenus's corporate event at ESMO and the related presentation about its botensilimab programmes are among the forward-looking statements made in this press release in accordance with the federal securities laws' safe harbour provisions: "May," "believes," "expects," "anticipates," "hopes," "intends," "plans," "estimates," "will," "establish," "potential," "best in class," and similar expressions are intended to identify forward-looking statements. These forward-looking statements contain risks and uncertainties that could dramatically affect how actual results turn out. The variables included in the Risk variables section of our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commision are only a few of the risks and uncertainties that we face. Agenus warns financial.