2. Academic Validation
  3. 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

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. doi: 10.1158/1078-0432.CCR-23-0475.
Sarah A Weiss 1,  Mario Sznol 1,  Montaser Shaheen 2,  Miguel-Ángel Berciano-Guerrero 3,  Eva Muñoz Couselo 4,  Delvys Rodríguez-Abreu 5,  Valentina Boni 6,  Lynn M Schuchter 7,  Maria Gonzalez-Cao 8,  Ana Arance 9,  Wei Wei 1,  Apar Kishor Ganti 10,  Ralph J Hauke 11,  Alfonso Berrocal 12,  Nicholas O Iannotti 13,  Frank J Hsu 14,  Harriet M Kluger 1
Affiliations

Affiliations

  • 1 Yale University School of Medicine, New Haven, Connecticut.
  • 2 University of Arizona Cancer Center, Tucson, Arizona.
  • 3 Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain.
  • 4 Vall d'Hebron University Hospital, Barcelona, Spain.
  • 5 Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain.
  • 6 START Madrid-CIOCC, Hospital Universitario HM Sanchinarro, Madrid, Spain.
  • 7 Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • 8 Instituto Oncológico, Quirón Dexeus University Hospital, Barcelona, Spain.
  • 9 Hospital Clínic Barcelona, Barcelona, Spain.
  • 10 VA Nebraska Western Iowa Healthcare System and University of Nebraska Medical Center, Omaha, Nebraska.
  • 11 Nebraska Cancer Specialists, Omaha, Nebraska.
  • 12 University General Hospital of Valencia, Valencia, Spain.
  • 13 Hematology Oncology Associates of the Treasure Coast, Port Saint Lucie, Florida.
  • 14 Apexigen America, Inc., San Carlos, California.
PMID: 37535056 DOI: 10.1158/1078-0432.CCR-23-0475
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. See related commentary by Wu and Luke, p. 9.

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