Lakhani, Nehal J, Papadopoulos, Kyriakos P, Johnson, Melissa Lynne, Park, Haeseong, Wang, Ding, Yap, Timothy A, Dowlati, Afshin, Maki, Robert G, Ulahannan, Susanna, Lynce, Filipa, Kelly, Karen, Williamson, Stephen, Malhotra, Jyoti, Chen, Shuquan, Gonzalez Ortiz, Ana, Jankovic, Vladimir, Paccaly, Anne, Masinde, Sheila, Mani, Jayakumar, Lowy, Israel, Gullo, Giuseppe, Sims, Tasha, Kroog, Glenn (December 2024) First-in-Human Dose-Escalation Study of Fianlimab, an Antilymphocyte Activation Gene-3 Antibody, with Cemiplimab in Patients with Advanced Malignancies. Clinical Cancer Research, 30 (24). pp. 5601-5611. ISSN 1078-0432
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Abstract
PURPOSE: Preclinical data indicate that fianlimab (antilymphocyte activation gene-3) plus cemiplimab (anti-PD-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. PATIENTS AND METHODS: Adult patients received 1 to 40 mg/kg of fianlimab plus 350 mg of cemiplimab every 3 weeks (Q3W) across various dose-escalation schedules. Primary objectives were the 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, in 87% of patients with fianlimab + cemiplimab, and in 87% of patients 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 1,600 mg Q3W (20 mg/kg in an 80-kg individual) is the selected dose for phase 2 and phase 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.
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