M9657
/ EMD Serono
- LARVOL DELTA
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March 06, 2024
M9657, a tumor-targeted anti-CD137 agonist, induced significant antitumor immunity in combination with anti-PD-1 antibody
(AACR 2024)
- "Anti-PD-(L)-1 antibodies can reverse the suppressive immune signals, and CD137 agonists can boost T cell activation, improving antigen presentation and cytokine release. The antitumor immunity of M9657 + pembrolizumab (anti-PD-1 antibody) combination therapy was assessed using in-vitro luciferase and ex-vivo functional assays. The combination of M9657 with anti-PD-(L)1 could overcome primary ICI therapy resistance and improve the antitumor efficacy of current anti-PD-(L)1 therapy in the clinic. Our findings support a combination strategy to combine M9657 with anti-PD-(L)1 in a clinical setting, potentially leading to enhanced antitumor immunity and improved patient outcomes. Future studies should investigate the safety and efficacy of this combination therapy in human patients."
Combination therapy • Oncology • CD8 • MSLN
December 13, 2023
M9657 is a bispecific tumor-targeted anti-CD137 agonist that induces MSLN-dependent antitumor immunity without liver inflammation.
(PubMed, Cancer Immunol Res)
- "Development of the first-generation CD137-agonist monotherapies utomilumab and urelumab was unsuccessful due to low antitumor efficacy mediated by the epitope recognized on CD137 or hepatotoxicity mediated by FcγR ligand-dependent CD137 activation, respectively. Compared with 3H3, a murine surrogate of urelumab, FS122m and chimeric M9657 displayed significantly lower on-target/off-tumor toxicity. Taken together, M9657 exhibits a promising profile for development as a tumor-targeting immune agonist with potent anticancer activity without systemic immune activation and associated hepatotoxicity."
IO biomarker • Journal • Hepatology • Oncology • CD8 • MSLN
March 14, 2023
Anti-tumor immunity of M9657, a conditional CD137 immune agonist, is correlated with mesothelin expression on tumor cells
(AACR 2023)
- "M9657 exhibits promising and potent MSLN-dependent conditional immune agonism, supporting its clinical investigation."
IO biomarker • Tumor cell • Oncology • CD8 • IFNG • MSLN • TNFRSF9
October 01, 2021
M9657, a novel tumor-targeted conditional anti-CD137 agonist displays MSLN-dependent anti-tumor immunity
(SITC 2021)
- "In clinical trials, the systemic administration of the 1st generation CD137 agonist monotherapies, utomilumab and urelumab, were suspended due to either low anti-tumor efficacy or hepatotoxicity mediated by recognized epitope on CD137 and FcγR ligand-dependent clustering. Comparing with 3H3, a Urelumab surrogate Ab, FS122m displayed an improved therapeutic window with significantly lower for on-target /off-tumor toxicity. Conclusions Taken together, M9657 exhibits a promising developability profile as a tumor-targeted immune agonist with potent anti-cancer activity, but without systemic immune activation."
IO biomarker • Oncology • BCL2L1 • MSLN
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