First-In-Human Dose-Escalation Study of Fianlimab, an Anti-Lymphocyte Activation Gene-3 Antibody, with Cemiplimab in patients with advanced malignancies.

Autor:	Lakhani NJ; START Midwest, Grand Rapids, Michigan, United States., Papadopoulos KP; START San Antonio, San Antonio, Texas, United States., Johnson ML; Sarah Cannon Research Instutite, Nashville, TN, United States., Park H; Dana-Farber Cancer Institute, Boston, MA, United States., Wang D; Clinical Trial Office, Detroit, Michigan, United States., Yap TA; The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Dowlati A; University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States., Maki RG; Memorial Sloan Kettering Cancer Center, New York, NY, United States., Ulahannan S; Stephenson Cancer Center, OUHSC, OKC, Oklahoma, United States., Lynce F; Dana-Farber/Harvard Cancer Center, Boston, MA, United States., Kelly K; University of California Davis Comprehensive Cancer Center, Sacramento, United States., Williamson S; University of Kansas Cancer Center, Fairway, Kansas, United States., Malhotra J; Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States., Chen S; Regeneron (United States), United States., Gonzalez Ortiz A; Regeneron (United States), United States., Jankovic V; Regeneron (United States), United States., Paccaly A; Regeneron Pharmaceuticals Inc., Tarrytown, NY, United States., Masinde S; Regeneron (United States), United States., Mani J; Regeneron (United States), United States., Lowy I; Regeneron Pharmaceuticals, Inc., New york, Ny, United States., Gullo G; Regeneron (United States), United States., Sims T; Regeneron (United States), Tarrytown, United States., Kroog G; Regeneron (United States), United States.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Oct 18. Date of Electronic Publication: 2024 Oct 18.
DOI:	10.1158/1078-0432.CCR-23-3883
Abstrakt:	Purpose: Preclinical data indicate that fianlimab (anti-lymphocyte activation gene-3) plus cemiplimab (anti-programmed cell death-1) enhances antitumor activity. Here, we report prespecified final analyses of the dose-escalation part of a first-in-human, phase 1 study (NCT03005782) of fianlimab as monotherapy and in combination with cemiplimab in patients with advanced malignancies. Experimental Design: Adult patients received fianlimab 1-40 mg/kg ± cemiplimab 350 mg every 3 weeks (Q3W) across various dose-escalation schedules. Primary objectives were rate of dose-limiting toxicities, adverse events (including immune-mediated), deaths, laboratory abnormalities, and pharmacokinetics. Secondary outcomes were objective response rate, best overall response, duration of response, and antidrug antibody variables. Results: Seventy-eight patients were enrolled (fianlimab + cemiplimab, n = 47; fianlimab monotherapy, n = 31). One patient treated with 3 mg/kg fianlimab + cemiplimab experienced dose-limiting toxicities, including increased blood creatine phosphokinase and myasthenic syndrome. No maximum tolerated dose was reached. Any-grade treatment-emergent adverse events occurred in 90% of patients with fianlimab monotherapy, 87% with fianlimab + cemiplimab, and 87% who transitioned from monotherapy to combination therapy. Fianlimab pharmacokinetics were dose-proportional, and similar in monotherapy and combination therapy. Across patients who received fianlimab + cemiplimab, five achieved a partial response; three of whom experienced a response after transitioning from monotherapy to combination therapy. Fianlimab 1600 mg Q3W (20 mg/kg in an 80 kg individual) is the selected dose for phase 2 and 3 studies. Conclusions: Fianlimab as monotherapy and in combination with cemiplimab demonstrated acceptable safety and preliminary antitumor activity, which is generally consistent with previous reports of cemiplimab.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu