New Phase I/II Data on the CD40 Antibody Sotigalimab in Combination With Pembrolizumab in Patients With Metastatic Melanoma
New data from an ongoing phase II trial evaluating first-line intratumoral administration of sotigalimab, a CD40 agonist antibody, in combination with systemic pembrolizumab, an anti–PD-1 antibody, in metastatic melanoma was presented by Bentebibel et al at the Society for Immunotherapy of Cancer (SITC) 2022 Annual Meeting (Abstract 782). Results showed that the combination therapy was well tolerated in the trial, and an improved best overall response rate was observed relative to the standard of care, pembrolizumab monotherapy. Broad innate and adaptive immune activation was observed in both local and distant (noninjected) lesions.
Adi Diab, MD
“While checkpoint inhibitors are the current standard of care for metastatic melanoma, many patients are unresponsive or develop resistance after initial tumor regression,” said Adi Diab, MD, Associate Professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center and principal investigator of the study. “Results from the ongoing phase II trial of intratumoral sotigalimab and the PD-1 inhibitor pembrolizumab showed a promising overall response rate, including responses achieved in PD-L1–negative tumors. Moreover, this encouraging antitumor activity correlated with treatment-induced immunologic changes, such as activated myeloid dendritic cells and macrophages, which support the mechanism of action and differentiated activity of sotigalimab—ultimately leading to inflammatory immune responses in the local injected tumor as well as distant noninjected lesions."
Key data and conclusions featured in the SITC presentation include:
- Safety and tolerability: Intratumoral administration of sotigalimab in combination with pembrolizumab was well tolerated. The most common adverse events were injection site reactions. Grade 3 immune-related adverse events were observed at a frequency similar to that reported with anti–PD-1 therapy alone. There were no dose-limiting toxicities and no discontinuations or deaths due to treatment-related events. No immunosuppressive therapy was needed.
- Efficacy: The objective response rate was 47% (n = 32) in all patients, including patients enrolled in the dose-escalation portion of the trial. At the recommended phase II dose of sotigalimab, the objective response rate was 50% (n = 24), which compares favorably to standard-of-care pembrolizumab alone (34%). Clinical responses were achieved in both PD-L1–negative tumors and patients with elevated lactate dehydrogenase.
- Immune Priming: Effects included rapid increases in activated macrophages and dendritic cells and an early upregulation of genes associated with antigen-presenting cells 24 hours post–sotigalimab administration followed by T-cell activation and expansion in the tumor microenvironment in local and distant tumor sites.
- Immune changes in the tumor microenvironment correlate with clinical response: Posttreatment analyses revealed increases in activated macrophages, dendritic cells, and CD8+ T cells correlated with clinical response.
Disclosure: For full disclosures of the study authors, visit jitc.bmj.com.
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