A phase I study of avelumab, palbociclib, and cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma
Michael J Dennis, Assuntina G Sacco, Yuchen Qi, Julie Bykowski, Emily Pittman, Ruifeng Chen, Karen Messer, Ezra E W Cohen, Kathryn A Gold, Michael J Dennis, Assuntina G Sacco, Yuchen Qi, Julie Bykowski, Emily Pittman, Ruifeng Chen, Karen Messer, Ezra E W Cohen, Kathryn A Gold
Abstract
Objectives: We aimed to test the safety of the CDK4/6 inhibitor palbociclib in combination with the EGFR inhibitor cetuximab and the PD-L1 inhibitor avelumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Materials and methods: This phase I study enrolled eligible adult patients with R/M HNSCC into three sequential single dose-escalation cohorts of palbociclib (75, 100, and 125 mg) PO daily on days 1 to 21 of a 28-day cycle in combination with avelumab 10 mg/kg IV every 2 weeks and cetuximab 400 mg/m2IV on day 1, then 250 mg/m2weekly thereafter. The study followed a 3 + 3 design with no intra-patient escalation. The primary objective was to identify the recommended phase II dose (RP2D); secondary objectives included overall response rate (ORR), duration of response (DOR), progression free survival (PFS), and overall survival (OS).
Results: Palbociclib in combination with avelumab and cetuximab was well tolerated, with rash and fatigue being the most common adverse events. A single dose-limiting toxicity was observed at the 125 mg dose of palbociclib: a grade 3 infusion reaction related to cetuximab. The RP2D of palbociclib is 125 mg, with avelumab and cetuximab at standard doses. The ORR by RECIST v1.1 was 42 %, the median DOR and OS have not been reached. Median PFS was 6.5 months.
Conclusions: The combination of avelumab, cetuximab, and palbociclib was well tolerated and supports further evaluation in patients with R/M HNSCC.
Clinical trial registration number: NCT03498378.
Keywords: Avelumab; Cetuximab; Head and neck cancer; Palbociclib; Squamous cell carcinoma.
Conflict of interest statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Copyright © 2022. Published by Elsevier Ltd.
Source: PubMed