Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/134357
Title: 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
Authors: Weiss, Sarah A.
Sznol, Mario
Shaheen, Montaser
Berciano-Guerrero, Miguel-Angel
Couselo, Eva Munoz
Rodríguez Abreu, Delvys 
Boni, Valentina
Schuchter, Lynn M.
Gonzalez-Cao, Maria
Arance, Ana
Wei, Wei
Ganti, Apar Kishor
Hauke, Ralph J.
Berrocal, Alfonso
Iannotti, Nicholas O.
Hsu, Frank J.
Kluger, Harriet M.
UNESCO Clasification: 32 Ciencias médicas
320713 Oncología
3209 Farmacología
Issue Date: 2024
Journal: Clinical Cancer Research 
Abstract: 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: We conducted a multicenter, 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 45.9+ and 26+ months, whereas the other three responders relapsed at 41.1, 18.7, and 18.4 months. The 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.
URI: http://hdl.handle.net/10553/134357
ISSN: 1078-0432
DOI: 10.1158/1078-0432.CCR-23-0475
Source: Clinical Cancer Research [ISSN 1078-0432], v. 30 (1), p. 74-81, (Enero 2024).
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