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

• Published in: Clinical cancer research 2023-02, Vol.29 (3), p.560-570
• Main Authors: Aggarwal, Charu, Saba, Nabil F, Algazi, Alain, Sukari, Ammar, Seiwert, Tanguy Y, Haigentz, Missak, Porosnicu, Mercedes, Bonomi, Marcelo, Boyer, Jean, Esser, Mark T, Cheng, Lily I, Agrawal, Sonia, Jennings, Emily C, Durham, Nicholas M, Fraser, Karl, Lissa, Delphine, Gong, Maozhen, Ceaicovscaia, Natalia, Gascó Hernández, Amaya, Kumar, Rakesh
• Format: Article
• Language: English
• Subjects: B7-H1 Antigen - genetics; Head and Neck Neoplasms - drug therapy; Human papillomavirus 16 - genetics; Human papillomavirus 18; Human Papillomavirus Viruses; Humans; Papillomavirus Infections - complications; Squamous Cell Carcinoma of Head and Neck - drug therapy
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-22-1987

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. 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). 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. 2-fold increase in tumor-infiltrating CD8+ T cells. MEDI0457 plus durvalumab was well tolerated. While the primary efficacy endpoint was not reached, clinical benefit was encouraging.