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
  • 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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