Pembrolizumab Plus Pepinemab Appears Safe for Advanced HNSCC

The combination of pembrolizumab (Keytruda) and pepinemab (Vaccinex) demonstrated a tolerable safety profile, according to interim data from patients with advanced, recurrent, or metastatic head and neck squamous cell carcinoma (HNSCC) treated in the frontline setting , reported Vaccinex, Inc., in a press release.

Pepinemab is humanized IgG4 monoclonal antibody inhibitor of semaphorin 4D (SEMA4D). Pepinemab has shown to promote infiltration/activation of dendritic cells/ CD8+ T-cells and reverses immunosuppression within the tumor in preclinical data.

This safety analysis was conducted within the phase 1b segment of the KEYNOTE B84 (NCT04815720) trial and served as a safety run-in to observe the tolerability of 20 mg/kg pepinemab with 200 mg pembrolizumab given every 3 weeks.1 The safety analysis was completed by the Data Safety Monitoring Board, which has recommended a phase 2 expansion.

“We are very pleased that the interim KEYNOTE B84 safety data indicated that the combination of pepinemab and Keytruda appears to be well tolerated,” stated Maurice Zauderer, PhD, president and chief executive officer, in a press release. “Vaccinex hopes that the combination of pepinemab and an anti–PD-1 therapy for the treatment of advanced HSNCC may result in improved patient benefits. There is strong rationale for development in HNSCC because these tumors express very high levels of SEMA4D, and we believe that preclinical data indicated that this contributes to disease pathology. We look forward to progressing with the recruitment of the phase 2 segment of the trial.”

The phase 1b segment aimed to find the recommended phase 2 dose among 3-6 patients. After testing the first 3 patients, the recommended dosing was found to be 20 mg/kg of pepinemab with 200 mg of pembrolizumab administered every 3 weeks.

The second segment of the study, phase 2, will enroll up to 62 patients across 19 trial sites in the US The primary objective of this expansion segment will be objective response rate, according to RECIST 1.1 in patients who are immunotherapy-naïve who have advanced HNSCC. The secondary objectives will be progression-free survival by RECIST 1.1, overall survival, and duration of response. The study will also evaluate pharmacokinetics, pharmacodynamics, immunogenicity of the combination, and several other biomarkers and genomic tumor signatures.

_Reference

_{Vaccinex reports phase Ib KEYNOTE B84 combination study of Keytruda and pepinemab in patients with advanced, recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) passes planned interim safety analysis. News release. Vaccinex Inc. January 4, 2022. Accessed January 4, 2021. https://bit.ly/3qQzMm3}