Safety and Efficacy of MEDI0457 plus Durvalumab in Patients with Human Papillomavirus-Associated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

• Type of Material: Article
• Authors: Charu Aggarwal, University of Pennsylvania; Nabil Saba, Emory University; Alain Algazi, University of California San Francisco; Ammar Sukari, Wayne State University; Tanguy Y Seiwert, Johns Hopkins University; Missak Haigentz, Rutgers State Univ; Mercedes Porosnicu, Wake Forest School of Medicine; Marcelo Bonomi, Ohio State University; Jean Boyer, Inovio Pharmaceuticals; Mark T Esser, AstraZeneca; Lily I Cheng, AstraZeneca; Sonia Agrawal, AstraZeneca; Emily C Jennings, AstraZeneca; Nicholas M Durham, AstraZeneca; Karl Fraser, AstraZeneca; Delphine Lissa, AstraZeneca; Maozhen Gong, AstraZeneca; Natalia Ceaicovscaia, AstraZeneca; Amaya Gascó Hernández, AstraZeneca; Rakesh Kumar, AstraZeneca
• Language: English
• Date: 2023-02-01
• Publisher: AMER ASSOC CANCER RESEARCH
• Publication Version: Final Published Version
• Copyright Statement: ©2022 The Authors; Published by the American Association for Cancer Research
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1158/1078-0432.CCR-22-1987
• Title of Journal or Parent Work: CLINICAL CANCER RESEARCH
• Volume: 29
• Issue: 3
• Start Page: 560
• End Page: 570
• Keywords: OPEN-LABEL; Science & Technology; METASTATIC HEAD; CANCER; VACCINE; RECURRENT; Oncology; BLOCKADE; PHASE-II; PEMBROLIZUMAB; Life Sciences & Biomedicine; PD-L1; SINGLE-ARM
• Research Categories: Health Sciences, Oncology

Abstract

PURPOSE: Tumoral programmed cell death ligand-1 (PD-L1) expression is common in human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). We assessed whether a DNA vaccine targeting HPV-16/18 E6/E7 with IL12 adjuvant (MEDI0457) combined with the PD-L1 inhibitor durvalumab could enhance HPV-specific T-cell response and improve outcomes in recurrent/metastatic HPV-16/18-associated HNSCC. PATIENTS AND METHODS: In this phase Ib/IIa study, immunotherapy-naïve patients with ≥1 previous platinum-containing regimen (neoadjuvant/adjuvant therapy or for recurrent/metastatic disease) received MEDI0457 7 mg intramuscularly with electroporation on weeks 1, 3, 7, and 12, then every 8 weeks, plus durvalumab 1,500 mg intravenously on weeks 4, 8, and 12, then every 4 weeks, until confirmed progression and/or unacceptable toxicity. Coprimary objectives were safety and objective response rate (ORR; H0: ORR ≤ 15%); secondary objectives included 16-week disease control rate (DCR-16), overall survival (OS), and progression-free survival (PFS). RESULTS: Of 35 treated patients, 29 were response evaluable (confirmed HPV-associated disease; received both agents). ORR was 27.6% [95% confidence interval (CI), 12.7-47.2; four complete responses, four partial responses]; responses were independent of PD-L1 tumor-cell expression (≥25% vs. <25%). DCR-16 was 44.8% (95% CI, 26.5-64.3). Median PFS was 3.5 months (95% CI, 1.9-9.0); median OS was 29.2 months (15.2-not calculable). Twenty-eight (80.0%) patients had treatment-related adverse events [grade 3: 5 (14.3%); no grade 4/5], resulting in discontinuation in 2 (5.7%) patients. HPV-16/18-specific T cells increased on treatment; 4 of 8 evaluable patients had a >2-fold increase in tumor-infiltrating CD8+ T cells. CONCLUSIONS: MEDI0457 plus durvalumab was well tolerated. While the primary efficacy endpoint was not reached, clinical benefit was encouraging.