{"doi":"10.1093/oncolo/oyad085","title":"Phase II Trial of MEDI0457 and Durvalumab for Patients With Recurrent/Metastatic Human Papillomavirus-Associated Cancers","abstract":"BACKGROUND: Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers. METHODS: Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg intravenously every 4 weeks. The primary endpoint was overall response (RECIST 1.1). In this Simon two-stage phase 2 trial (Ho: p < 0.15; Ha: p ≥ 0.35), ≥2 responses were needed in both cervical and non-cervical cohorts during the first stage for the trial to proceed to stage 2 with an additional 25 patients (34 total) enrolled. RESULTS: Twenty-one patients (12 cervical, 7 anal, and 2 penile) were evaluable for toxicity and 19 for response Overall response rate was 21% (95% CI, 6%-46%) among evaluable patients. Disease control rate was 37% (95% CI, 16%-62%). Median duration of response among responders was 21.8 months (95% CI, 9.7%-not estimable). Median progression-free survival was 4.6 months (95% CI, 2.8%-7.2%). Median overall survival was 17.7 months (95% CI, 7.6%-not estimable). Grades 3-4 treatment-related adverse events occurred in 6 (23%) participants. CONCLUSIONS: The combination of MEDI0457 and durvalumab demonstrated acceptable safety and tolerability in patients with advanced HPV-16/18 cancers. The low ORR among patients with cervical cancer led to study discontinuation despite a clinically meaningful disease control rate.","journal":"The Oncologist","year":2023,"id":331493,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":256637,"name":"Amir A. Jazaeri","orcid":"0000-0003-4335-4151","position":1,"is_corresponding":false},{"id":233757,"name":"Shannon N. Westin","orcid":"0000-0002-1922-0156","position":2,"is_corresponding":false},{"id":302044,"name":"Curtis A. Pettaway","orcid":"0000-0003-1697-1840","position":3,"is_corresponding":false},{"id":1056854,"name":"Solly George","orcid":null,"position":4,"is_corresponding":false},{"id":868765,"name":"Ryan Huey","orcid":"0000-0002-7887-8484","position":5,"is_corresponding":false},{"id":922753,"name":"Michaela Onstad Grinsfelder","orcid":"0000-0001-5192-2273","position":6,"is_corresponding":false},{"id":453077,"name":"Aaron Shafer","orcid":"0000-0003-2565-0264","position":7,"is_corresponding":false},{"id":461070,"name":"Benny Johnson","orcid":"0000-0003-3683-8115","position":8,"is_corresponding":false},{"id":704324,"name":"David Vining","orcid":null,"position":9,"is_corresponding":false},{"id":302041,"name":"Ming Guo","orcid":"0000-0002-6773-1145","position":10,"is_corresponding":false},{"id":268549,"name":"Bryan Fellman","orcid":"0000-0002-1810-5762","position":11,"is_corresponding":false},{"id":256630,"name":"Michael Frumovitz","orcid":"0000-0002-0810-2648","position":12,"is_corresponding":false},{"id":461072,"name":"Van K. Morris","orcid":"0000-0002-4911-2252","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-19T01:09:19.317824Z","pmid":"37104874","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}