%0 Journal Article
%A Weiss, Sarah A
%A Sznol, Mario
%A Shaheen, Montaser
%A Berciano-Guerrero, Miguel-Angel
%A Muñoz-Couselo, Eva
%A Rodriguez-Abreu, Delvys
%A Boni, Valentina
%A Schuchter, Lynn M
%A Gonzalez-Cao, Maria
%A Arance, Ana
%A Wei, Wei
%A Ganti, Apar Kishor
%A Hauke, Ralph J
%A Berrocal, Alfonso
%A Iannotti, Nicholas O
%A Hsu, Frank J
%A Kluger, Harriet M
%T A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Confirmed Disease Progression on Anti-PD-1 Therapy.
%D 2023
%@ 1557-3265
%U https://hdl.handle.net/10668/28504
%X Purpose: Disease progression during or after anti-PD-1-based treatment is common in advanced melanoma. Sotigalimab is a CD40 agonist antibody with a unique epitope specificity and Fc receptor binding profile optimized for activation of CD40-expressing antigen-presenting cells. Preclinical data indicated that CD40 agonists combined with anti-PD1 could overcome resistance to anti-PD-1. Patients and Methods: Weconductedamulticenter, open-label, phase II trial to evaluate the combination of sotigalimab 0.3 mg/kg and nivolumab 360 mg every 3 weeks in patients with advanced melanoma following confirmed disease progression on a PD-1 inhibitor. The primary objective was to determine the objective response rate (ORR). Results: Thirty-eight subjects were enrolled and evaluable for safety. Thirty-three were evaluable for activity. Five confirmed partial responses (PR) were observed for an ORR of 15%. Two PRs are ongoing at 45.9þ and 26þ months, whereas the other three responders relapsed at 41.1, 18.7, and 18.4 months. The median durationofresponsewasatleast26months.Twoadditionalpatients had stable disease for >6 months. Thirty-four patients (89%) experienced at least one adverse event (AE), and 13% experienced a grade 3 AE related to sotigalimab. The most common AEs were pyrexia,chills, nausea,fatigue, pruritus,elevatedliverfunction, rash, vomiting, headache, arthralgia, asthenia, myalgia, and diarrhea. There were no treatment-related SAEs, deaths, or discontinuation of sotigalimab due to AEs. Conclusions: Sotigalimab plus nivolumab had a favorable safety profile consistent with the toxicity profiles of each agent. The combination resulted in durable and prolonged responses in a subset of patients with anti-PD-1-resistant melanoma, warranting further evaluation in this setting.
%K Nivolumab
%K Melanoma
%K Sotigalimab
%K Immune Checkpoint Inhibitors
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