About this item:

81 Views | 29 Downloads

Author Notes:

Charu Aggarwal, Abramson Cancer Center, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104. Phone: 215-662-6318: E-mail: charu.aggarwal@pennmedicine.upenn.edu

C. Aggarwal: Conceptualization, resources, data curation, formal analysis, supervision, validation, investigation, visualization, methodology, writing–original draft, writing–review and editing. N.F. Saba: Resources, data curation, formal analysis, writing–original draft, writing–review and editing. A. Algazi: Supervision, investigation, writing–review and editing. A. Sukari: Data curation, formal analysis, supervision, investigation, writing–review and editing. T.Y. Seiwert: Investigation, project administration, writing–review and editing. M. Haigentz: Data curation, investigation, writing–review and editing. M. Porosnicu: Data curation, investigation, writing–review and editing. M. Bonomi: Data curation, investigation, writing–review and editing. J. Boyer: Data curation, writing–review and editing. M.T. Esser: Conceptualization, data curation, formal analysis, writing–review and editing. L.I. Cheng: Investigation, writing–review and editing. S. Agrawal: Formal analysis, visualization, writing–review and editing. E.C. Jennings: Formal analysis, visualization, writing–review and editing. N.M. Durham: Conceptualization, data curation, formal analysis, supervision, investigation, visualization, writing–review and editing. K. Fraser: Conceptualization, formal analysis, writing–review and editing. D. Lissa: Data curation, formal analysis, writing–review and editing. M. Gong: Formal analysis, visualization, writing–review and editing. N. Ceaicovscaia: Formal analysis, visualization, writing–review and editing. A. Gascó Hernández: Conceptualization, data curation, formal analysis, writing–review and editing. R. Kumar: Conceptualization, resources, supervision, project administration, writing–review and editing.

The authors would like to thank the patients who participated in the study, and their families and caregivers. They would also like to thank all study sites and personnel. This study (NCT03162224) was funded by AstraZeneca, the manufacturer of MEDI0457 and durvalumab. Medical writing support, under the direction of the authors, was provided by Susanne Gilbert of Ashfield MedComms, an Ashfield Health company, and was funded by AstraZeneca. The publication costs of this article were defrayed in part by the payment of publication fees. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 USC section 1734.

C. Aggarwal reports personal fees from Genentech, Lilly, Celgene, Merck, AstraZeneca, Blueprint Genetics, Shionogi, Daiichi Sankyo/AstraZeneca, Regeneron/Sanofi, Eisai, Turning Point, Pfizer, Janssen, and Boehringer Ingelheim; and grants from Genentech/Roche, Incyte, Macrogenics, Merck Sharp & Dohme, and AstraZeneca/MedImmune outside the submitted work. N.F. Saba reports advisory roles to Merck, BMS, Eisai, Exelixis, AstraZeneca, Novartis, Vaccinex, and GSK. A. Algazi reports other support from AstraZeneca during the conduct of the study; personal fees and other support from OncoSec, Onchilles, Valitor, and Sensei; and personal fees from Worldwide Clinical Trials, Radmetrix, Venn, and IAG outside the submitted work. T.Y. Seiwert reports grants and personal fees from Merck/MSD, Nanobiotix, and Kura; personal fees from Innate, CUE-101, VIR, Eisai, Bayer, Sanofi, BostonGene, and Nektar; and grants from Roche, AstraZeneca, Regeneron, BMS, and Dracen outside the submitted work. M. Haigentz reports personal fees from AstraZeneca, Blueprint Medicines, Coherus Biosciences, Jazz Pharmaceuticals, and Takeda Pharmaceuticals outside the submitted work. M. Porosnicu reports other support from AstraZeneca during the conduct of the study; and other support from AstraZeneca and Boehringer Ingelheim outside the submitted work. M. Bonomi reports grants from Regeneron and personal fees from Merck outside the submitted work. M.T. Esser is an employee of and owns stock in AstraZeneca. S. Agrawal reports personal fees from AstraZeneca outside the submitted work. E.C. Jennings reports personal fees from AstraZeneca outside the submitted work. N.M. Durham reports other support from AstraZeneca during the conduct of the study. D. Lissa reports personal fees from AstraZeneca during the conduct of the study; and personal fees from AstraZeneca outside the submitted work. M. Gong reports personal fees from AstraZeneca during the conduct of the study; and personal fees from AstraZeneca outside the submitted work. N. Ceaicovscaia reports other support from AstraZeneca during the conduct of the study; and other support from AstraZeneca outside the submitted work. R. Kumar is an employee of AstraZeneca. No disclosures were reported by the other authors.

Subject:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • OPEN-LABEL
  • METASTATIC HEAD
  • SINGLE-ARM
  • PHASE-II
  • RECURRENT
  • VACCINE
  • CANCER
  • BLOCKADE
  • PEMBROLIZUMAB
  • PD-L1

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

Show all authors Show less authors

Tools:

Journal Title:

CLINICAL CANCER RESEARCH

Volume:

Volume 29, Number 3

Publisher:

, Pages 560-570

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

©2022 The Authors; Published by the American Association for Cancer Research

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Export to EndNote