RT Journal Article
T1 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.
A1 Weiss, Sarah A
A1 Sznol, Mario
A1 Shaheen, Montaser
A1 Berciano-Guerrero, Miguel-Angel
A1 Muñoz-Couselo, Eva
A1 Rodriguez-Abreu, Delvys
A1 Boni, Valentina
A1 Schuchter, Lynn M
A1 Gonzalez-Cao, Maria
A1 Arance, Ana
A1 Wei, Wei
A1 Ganti, Apar Kishor
A1 Hauke, Ralph J
A1 Berrocal, Alfonso
A1 Iannotti, Nicholas O
A1 Hsu, Frank J
A1 Kluger, Harriet M
K1 Nivolumab
K1 Melanoma
K1 Sotigalimab
K1 Immune Checkpoint Inhibitors
AB 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.
PB American Association for Cancer Research
SN 1557-3265
YR 2023
FD 2023-08-03
LK https://hdl.handle.net/10668/28504
UL https://hdl.handle.net/10668/28504
LA en
NO Weiss SA, Sznol M, Shaheen M, Berciano-Guerrero MÁ, Couselo EM, Rodríguez-Abreu D, et al. 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. Clin Cancer Res. 2024 Jan 5;30(1):74-81
NO The study was funded by Apexigen. Drug support was provided by Apexigen and Bristol Myers Squibb. We acknowledge research funding in part from the Yale Calabresi Immuno-oncology Training Program (K12CA215110; to S.A. Weiss) and the Yale SPORE in Skin Cancer (P50 CA121974; to H.M. Kluger).
DS RISalud
RD Jul 3, 2025