Biomaterial Database

Safety and Efficacy of MEDI0457 plus Durvalumab in Patients with Human Papillomavirus-Associated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma. 2023

Charu Aggarwal, and Nabil F Saba, and Alain Algazi, and Ammar Sukari, and Tanguy Y Seiwert, and Missak Haigentz, and Mercedes Porosnicu, and Marcelo Bonomi, and Jean Boyer, and Mark T Esser, and Lily I Cheng, and Sonia Agrawal, and Emily C Jennings, and Nicholas M Durham, and Karl Fraser, and Delphine Lissa, and Maozhen Gong, and Natalia Ceaicovscaia, and Amaya Gascó Hernández, and Rakesh Kumar

Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.

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. <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. MEDI0457 plus durvalumab was well tolerated. While the primary efficacy endpoint was not reached, clinical benefit was encouraging.

UI	MeSH Term	Description	Entries
D006258	Head and Neck Neoplasms	Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)	Cancer of Head and Neck,Head Cancer,Head Neoplasm,Head and Neck Cancer,Head and Neck Neoplasm,Neck Cancer,Neck Neoplasm,Neck Neoplasms,Neoplasms, Upper Aerodigestive Tract,UADT Neoplasm,Upper Aerodigestive Tract Neoplasm,Upper Aerodigestive Tract Neoplasms,Cancer of Head,Cancer of Neck,Cancer of the Head,Cancer of the Head and Neck,Cancer of the Neck,Head Neoplasms,Head, Neck Neoplasms,Neoplasms, Head,Neoplasms, Head and Neck,Neoplasms, Neck,UADT Neoplasms,Cancer, Head,Cancer, Neck,Cancers, Head,Cancers, Neck,Head Cancers,Neck Cancers,Neoplasm, Head,Neoplasm, Neck,Neoplasm, UADT,Neoplasms, UADT
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077195	Squamous Cell Carcinoma of Head and Neck	The most common type of head and neck carcinoma that originates from cells on the surface of the NASAL CAVITY; MOUTH; PARANASAL SINUSES, SALIVARY GLANDS, and LARYNX. Mutations in TNFRSF10B, PTEN, and ING1 genes are associated with this cancer.	HNSCC,Head And Neck Squamous Cell Carcinomas,Hypopharyngeal Squamous Cell Carcinoma,Laryngeal Squamous Cell Carcinoma,Oral Cavity Squamous Cell Carcinoma,Oral Squamous Cell Carcinoma,Oral Squamous Cell Carcinomas,Oral Tongue Squamous Cell Carcinoma,Oropharyngeal Squamous Cell Carcinoma,Squamous Cell Carcinoma of Larynx,Squamous Cell Carcinoma of the Larynx,Squamous Cell Carcinoma of the Mouth,Squamous Cell Carcinoma of the Nasal Cavity,Carcinoma, Squamous Cell of Head and Neck,Head and Neck Squamous Cell Carcinoma,Squamous Cell Carcinoma of the Head and Neck,Squamous Cell Carcinoma, Head And Neck
D000094302	Human Papillomavirus Viruses	A large group of viruses that cause HUMAN PAPILLOMAVIRUS INFECTION, e.g., GENITAL WARTS and cancer of the CERVIX; VAGINA; VULVA; ANUS; or OROPHARYNX. Most common clinically important human papilloma viruses are taxonomically members of ALPHAPAPILLOMAVIRUS and GAMMAPAPILLOMAVIRUS.	HPV Human Papillomavirus,Human Papillomavirus,HPV, Human Papillomavirus Viruses,Human Papilloma Virus,HPV Human Papillomaviruses,Human Papilloma Viruses,Human Papillomavirus Virus,Human Papillomavirus, HPV,Human Papillomaviruses,Human Papillomaviruses, HPV,Papilloma Virus, Human,Papillomavirus Virus, Human,Virus, Human Papilloma,Virus, Human Papillomavirus
D052161	Human papillomavirus 18	A type of human papillomavirus especially associated with malignant tumors of the genital and RESPIRATORY MUCOSA.	Alphapapillomavirus 7,HPV 18,HPV18,Human papillomavirus - 18,HPV-18,Human papillomavirus type 18
D052162	Human papillomavirus 16	A type of ALPHAPAPILLOMAVIRUS especially associated with malignant tumors of the CERVIX and the RESPIRATORY MUCOSA.	HPV 16,HPV16,Human papillomavirus - 16,Human papillomavirus type 16,human papillomavirus type 16 HPV 16,human papillomavirus type 16 HPV16,HPV-16,HPV 16s,HPV16s
D060890	B7-H1 Antigen	An inhibitory B7 antigen that contains V-type and C2 type immunoglobulin domains. It has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN and provides negative signals that control and inhibit T-cell responses. It is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.	Antigens, CD274,PD-L1 Protein,Programmed Cell Death 1 Ligand 1 Protein,Programmed Death Ligand 1,B7-H1 Immune Costimulatory Protein,B7H1 Immune Costimulatory Protein,CD274 Antigen,PD-L1 Costimulatory Protein,Programmed Cell Death 1 Ligand 1,Antigen, B7-H1,Antigen, CD274,B7 H1 Antigen,B7 H1 Immune Costimulatory Protein,CD274 Antigens,Costimulatory Protein, PD-L1,PD L1 Costimulatory Protein,PD L1 Protein
D030361	Papillomavirus Infections	Neoplasms of the skin and mucous membranes caused by papillomaviruses. They are usually benign but some have a high risk for malignant progression.	HPV Infection,Human Papillomavirus Infection,HPV Infections,Human Papillomavirus Infections,Papillomavirus Infection,Papillomavirus Infection, Human,Papillomavirus Infections, Human