A Phase II Trial of the CD40 Agonist Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Disease Progression on Anti-PD-1
Mené sur 38 patients atteints d'un mélanome de stade avancé ou métastatique, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du sotigalimab (un agoniste de CD40) en combinaison avec le nivolumab après l'échec d'un traitement par anti-PD-1
Purpose: Disease progression during or after anti-PD-1-based treatment is common in advanced melanoma. Sotigalimab is a CD40 agonist antibody with 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. Methods: We conducted a multi-center, open-label, phase II trial to evaluate the combination of sotigalimab 0.3mg/kg and nivolumab 360mg q3wk in patients with advanced melanoma following confirmed disease progression on anti-PD-1. 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 45.9+ and 26+ months while the other 3 responders relapsed at 41.1, 18.7, and 18.4 months. Median duration of response was at least 26 months. Two additional patients 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, elevated liver function, 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.