R/M HNSCC patients (pts) who have progressed on platinum-based chemotherapy have a poor prognosis and limited therapeutic options. Programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) are frequently up-regulated in several tumor types, including HNSCC. The global, single-arm, Phase 2 HAWK study (NCT02207530) evaluated the anti-PD-L1 immunotherapy durvalumab as monotherapy in PD-L1 high pts with R/M HNSCC who have failed platinum-based chemotherapy.
Immunotherapy-naïve pts aged ≥18 years with confirmed PD-L1 high protein expression (≥25% of tumor cells [TCs] using the Ventana SP263 assay) who had progression or recurrence during/after 1 platinum-based regimen for R/M HNSCC received durvalumab 10 mg/kg IV every 2 weeks up to 12 months or until progression, starting another anticancer therapy, consent withdrawal, or unacceptable toxicity. The primary endpoint was objective response rate (ORR; blinded independent central review, RECIST v1.1); secondary endpoints included progression-free survival (PFS) and overall survival (OS).
As of Sept 26, 2016, 112 pts from 12 countries had received treatment (median age 60 years, 71.4% male, 34.7% human papillomavirus [HPV]+, and 61.6% current/former smokers). Median durations of treatment and follow-up were 3.45 and 5.96 months, respectively. Among evaluable pts (n = 111), ORR was 13.5% (95% CI 7.8–21.3) overall and 26.5% (95% CI 12.9–44.4) and 7.9% (95% CI 2.6–17.6) for HPV+ and HPV- pts, respectively; among responders (n = 15), 12 (80%) had an ongoing response at data cutoff (DCO). 35 pts (31.5%) had stable disease ≥8 weeks. Median PFS was 2.3 months (95% CI 1.9–3.7) and 34 pts (30.4%) were alive at DCO (OS data were immature). The incidence of grade ≥3 treatment-related adverse events (AEs) was 9.8% and no treatment-related AEs led to death. 88 pts (78.6%) discontinued initial study treatment, 65 (58%) due to progressive disease and 10 (8.9%) due to all-causality AEs.
Durvalumab demonstrated promising antitumor activity with an acceptable safety profile in PD-L1 high pts with R/M HNSCC, supporting its potential use, and the opportunity to improve efficacy, in combination therapy.
Clinical trial identification
NCT02207530 (release date: August 1, 2014)
Legal entity responsible for the study
D. Zandberg: PI at UMGCCC for trials by Medimmune, AstraZeneca, Merck, Macrogenics, Bristol-Myers Squib, Gliknik. A. Algazi: UCSF receive research funding on my behalf from AstraZeneca, Merck, Bristol-Myers Squib, MedImmune, Acerta, OncoSec, Novartis. A. Jimeno: Consultant for AstraZeneca, one presentation at research meeting in January 2016 J.S. Good: Corporate sponsored research: AstraZeneca and Honoraria: Eisai, Bayer, Sirtex, BTG J. Fayette: Honoraria: Bristol-Myers Squib, AstraZeneca. N. Ready: Consultant: AstraZeneca, Bristol-Myers Squib, Merck, Celgene, Abbvie and Honoraria: Bristol-Myers Squib, Abbvie. P.M. Clement: Speakers’ Bureau and Corporate sponsored research: AstraZeneca. T. Goswmi, A. Jarkowski, J.M. Armstrong: Employee & Shareholder of AstraZeneca. K. Asubonteng: Employee & Shareholder of AstraZeneca. Corporate sponsored research: AstraZeneca. G. Melillo: Employee & Shareholder of AstraZeneca. R. Mesía: Speakers’ Bureau: Merck, SL and Consultant: Merck, SL, MSD, Bayer, AstraZeneca, Bristol. All other authors have declared no conflicts of interest.