Neoadjuvant pepinemab in combination with nivolumab and/or ipilimumab in resectable metastatic melanoma: a pilot biomarker-driven trial

Here we evaluated pepinemab, a Semaphorin 4D (SEMA4D)–blocking antibody, in combination with anti-PD1 nivolumab and/or anti-CTLA4 ipilimumab in a pilot biomarker-driven neoadjuvant trial (NCT03769155) for patients with resectable metastatic melanoma. The primary endpoint was to determine if pepinemab combined with ICIs modulates phenotypic properties within the tumor microenvironment in a manner that enhances T effector cell infiltration.

Secondary endpoints included safety and tolerability, pathological response rates and radiographical response. Patients received two neoadjuvant doses followed by curative-intent surgery and one year of adjuvant nivolumab. Pepinemab-containing regimens demonstrated manageable toxicity profiles and did not delay or preclude curative-intent surgical resection in the 38 patients treated.