651O - Pembrolizumab (pembro) + carboplatin (carbo) + paclitaxel (pacli) as first-line (1L) therapy in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Phase VI KEYNOTE-B10 study

Background

Based on the phase 3 KEYNOTE-048 trial, 1L SOC treatment (tx) for R/M HNSCC, regardless of PD-L1 status, is pembro + platinum + 5-FU. 5-FU alternatives are needed because of associated cardiovascular, dihydropyrimidine dehydrogenase deficiency–related toxicities and patient (pt) inconvenience, costs, and complications associated with continuous 4-day infusion. In clinical studies, platinum + pacli was no less efficacious than platinum + 5-FU in R/M HNSCC. We present initial results of the first global prospective trial of pembro + carbo + pacli in 1L R/M HNSCC.

Methods

In the ongoing phase 4 KEYNOTE-B10 trial (NCT04489888), pts with previously untreated, R/M HNSCC regardless of tumor PD-L1 status and ECOG PS 0/1 received pembro 200 mg IV Q3W, carbo AUC 5 mg/mL/min IV Q3W, and pacli 175 mg/m² IV Q3W or 100 mg/m² IV Q1W on days 1 and 8. Tx continued for ≤35 cycles of pembro, ≤6 cycles of carbo and pacli, or until PD, unacceptable toxicity, or pt withdrawal. Primary end point: ORR per RECIST v1.1 by BICR. Secondary end points: DOR and PFS by BICR, OS, safety and tolerability. Efficacy analysis was based on first 82 treated pts to ensure sufficient follow-up. Safety was analyzed in all treated pts.

Results

At March 16, 2022, data cutoff, 92 of 100 planned pts were enrolled; 41 remained on tx and 51 discontinued, most because of PD (31 of 51 pts). Median follow-up was 8.2 mo (range, 0.3-15.8). Confirmed ORR was 43% (95% CI, 32-54). Median OS was 12.1 mo (95% CI, 10-NR). For all treated pts (n = 92), any-grade TRAEs occurred in 96%, most commonly decreased neutrophil count (57%), anemia (43%), and fatigue (40%). Grade 3-5 TRAEs occurred in 71% of pts; 2 were grade 5 (sepsis; hypersensitivity reaction). Table: 651O

BICR, blinded independent central review; NR, not reached."+" indicates there is no progressive disease by the time of last disease assessment

Conclusions

Pembro + carbo + pacli showed antitumor activity with a manageable safety profile, suggesting this 5-FU-free regimen may be comparable to historical 1L SOC and may expand tx options for 1L R/M HNSCC.

Clinical trial identification

NCT04489888, release date July 28, 2020.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Mallory Campbell, PhD and Matthew Grzywacz, PhD, of ApotheCom (Yardley, PA, USA).

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

M.R. Dzienis: Financial Interests, Personal, Advisory Board: MSD, Novartis; Financial Interests, Personal, Other, Honoraria: BMS, Novartis; Financial Interests, Personal, Other, Educational support: Novartis, Roche. A.R. Hansen: Financial Interests, Institutional, Principal Investigator: Novartis, BMS, Pfizer, Boehringer Ingelheim, Roche, Genentech, AstraZeneca, MedImmune, Merck, GSK; Financial Interests, Personal, Advisory Board: AstraZeneca, Merck, GSK; Financial Interests, Institutional, Research Grant: Karyopharm. A.J. Joshi: Non-Financial Interests, Personal, Invited Speaker: Ipsen; Non-Financial Interests, Personal, Advisory Board: Ipsen, Amgen; Non-Financial Interests, Personal, Sponsor/Funding: MSD-Australia, Roche, Janssen-Cilag. J.S. Mccarthy: Financial Interests, Personal, Advisory Board: Merck, Pfizer, Ipsen, BMS. N. Naicker: Financial Interests, Personal, Full or part-time Employment: MSD. Y. Sidi, B. Gumuscu: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. G. De Castro Jr.: Financial Interests, Personal and Institutional, Speaker’s Bureau: Merck Serono, Roche, Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: Merck Serono, Roche, Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, GSK; Financial Interests, Personal and Institutional, Other: Merck Serono; Financial Interests, Personal and Institutional, Principal Investigator: Merck Sharp & Dohme, AstraZeneca, GSK. All other authors have declared no conflicts of interest.