A phase I study of avelumab, palbociclib, and cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma. (December 2022)

• Record Type: Journal Article
• Authors: Dennis, Michael J.; Sacco, Assuntina G.; Qi, Yuchen; Bykowski, Julie; Pittman, Emily; Chen, Ruifeng; Messer, Karen; Cohen, Ezra E.W.; Gold, Kathryn A.
• Is Part Of: Oral oncology. Volume 135(2022)
• Publication Date: 2022-12
• Subjects: Palbociclib -- Cetuximab -- Avelumab -- Head and neck cancer -- Squamous cell carcinoma; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2022.106219
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: Palbociclib, avelumab, and cetuximab was well tolerated in R/M HNSCC. No unexpected toxicities were observed. Promising response rates were seen (ORR 42%) 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/m 2 IV on day 1, then 250 mg/m 2 weekly 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.