A Phase I Study of the CDK4/6 Inhibitor, Palbociclib in Combination with Cetuximab and Radiotherapy (IMRT) for Locally Advanced Head and Neck Squamous Cell Carcinoma
We conducted a phase I dose escalation study (NCT03024489) using a classical 3+3 design to determine safety, tolerability, and maximum tolerated dose (MTD) of palbociclib, cetuximab, and IMRT combination. At the recommended phase 2 dose (RP2D), additional p16-negative patients were enrolled. The primary objective of this study was to describe the safety and tolerability of the combination therapy of palbociclib, cetuximab, and IMRT for locally advanced HNSCC, and estimate the RP2D. Secondary objectives included preliminary efficacy and exploration of potential biomarkers associated with the combination therapy. For each sample, 500ng of FFPE DNA was subjected to the Axen cancer panel 2, which contains 171 cancer-associated genes (Supplementary Table 1). Clinical grade sequencing was performed using the Illumina NovaSeq 6000 sequencer (Ilumina, Inc., USA) at an average coverage of at least 2000x. All sequencing assays were conducted in a CLIA-certified laboratory (Macrogen, Inc., South Korea). The MuTect2 and GATK4 pipelines were utilized to detect single-nucleotide variants (SNV), indels, and copy-number variations (CNV).