{"doi":"10.1002/cncr.35063","title":"Phase 1/2 trial of avelumab combined with utomilumab (4‐1BB agonist), PF‐04518600 (OX40 agonist), or radiotherapy in patients with advanced gynecologic malignancies","abstract":"BACKGROUND: Immune checkpoint blockade has shown mixed results in advanced/recurrent gynecologic malignancies. Efficacy may be improved through costimulation with OX40 and 4-1BB agonists. The authors sought to evaluate the safety and efficacy of avelumab combined with utomilumab (a 4-1BB agonist), PF-04518600 (an OX40 agonist), and radiotherapy in patients with recurrent gynecologic malignancies. METHODS: The primary end point in this six-arm, phase 1/2 trial was safety of the combination regimens. Secondary end points included the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors and immune-related Response Evaluation Criteria in Solid Tumors, the disease control rate (DCR), the duration of response, progression-free survival, and overall survival. RESULTS: Forty patients were included (35% with cervical cancer, 30% with endometrial cancer, and 35% with ovarian cancer). Most patients (n = 33; 83%) were enrolled in arms A-C (no radiation). Among 35 patients who were evaluable for efficacy, the ORR was 2.9%, and the DCR was 37.1%, with a median duration of stable disease of 5.4 months (interquartile range, 4.1-7.3 months). Patients with cervical cancer in arm A (avelumab and utomilumab; n = 9 evaluable patients) achieved an ORR of 11% and a DCR of 78%. The median progression-free survival was 2.1 months (95% CI, 1.8-3.5 months), and overall survival was 9.4 months (95% CI, 5.6-11.9 months). No dose-limiting toxicities or grade 3-5 immune-related adverse events were observed. CONCLUSIONS: The findings from this trial highlight that, in heavily pretreated patients with gynecologic cancer, even multidrug regimens targeting multiple immunologic pathways, although safe, did not produce significant responses. A DCR of 78% in patients with cervical cancer who received avelumab and utomilumab indicates that further research on this combination in select patients may be warranted.","journal":"Cancer","year":2023,"id":338916,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"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":1071929,"name":"Jibran Ahmed","orcid":"0000-0002-3412-7689","position":1,"is_corresponding":false},{"id":266106,"name":"Bettzy Stephen","orcid":"0000-0003-1653-2012","position":2,"is_corresponding":false},{"id":258839,"name":"Sarina A. 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Dumbrava","orcid":"0000-0002-1959-0536","position":12,"is_corresponding":false},{"id":1071930,"name":"Yali Yang","orcid":"0000-0003-4597-2615","position":13,"is_corresponding":false},{"id":291127,"name":"Juhee Song","orcid":"0000-0002-8688-4104","position":14,"is_corresponding":false},{"id":70220,"name":"Funda Meric‐Bernstam","orcid":"0000-0001-6816-6072","position":15,"is_corresponding":false},{"id":256637,"name":"Amir A. Jazaeri","orcid":"0000-0003-4335-4151","position":16,"is_corresponding":false},{"id":266105,"name":"Aung Naing","orcid":"0000-0002-4803-8513","position":17,"is_corresponding":false},{"id":328713,"name":"Anne Knisely","orcid":"0000-0003-4200-2293","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T01:10:40.496978Z","pmid":"37864520","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":[]}