{"doi":"10.1136/jitc-2024-009074","title":"Phase II basket trial of Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: adrenocortical carcinoma cohort","abstract":"OBJECTIVES: Multiple common cancers benefit from immunotherapy; however, less is known about efficacy in rare tumors. We report the results of the adrenocortical carcinoma cohort of NCI/SWOG S1609 Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors. DESIGN/SETTING: A prospective, phase 2 clinical trial of ipilimumab plus nivolumab was conducted by the SWOG Early Therapeutics and Rare Cancers Committee for multiple rare tumor cohorts across >1,000 National Clinical Trial Network sites. PARTICIPANTS: 21 eligible patients were registered. Median age was 53 years (range 26-69); 16 (76%) were women. INTERVENTIONS: Ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks was administered until disease progression, symptomatic deterioration, treatment delay for any reason >56 days, unacceptable or immune-related toxicity with inability to decrease prednisone to <10 mg daily, or per patient request. MAIN OUTCOME MEASURES: The primary endpoint was the overall response rate (ORR) (RECIST V.1.1). Secondary endpoints include clinical benefit rate (CBR) (includes stable disease (SD)>6 months), progression-free survival (PFS), overall survival (OS), and toxicity. Immune-related outcomes included immune ORR (iORR), immune CBR (iCBR), and immune PFS (iPFS). A two-stage design was used assuming: null=5% alternative=30%, n=6 in the first stage, 16 max, one-sided alpha=13%. RESULTS: The median number of prior therapy lines was 2 (range: 1-9). 3 of 21 patients attained confirmed partial response (PR) (ORR=14%). In addition, one patient had an unconfirmed PR; one, stable disease (SD)>6 months; one, immune-related RECIST (iRECIST) PR (iPR); and one patient attained iSD>6 months: clinical benefit rate (response or SD>6 months)=5/21 (24%), iORR=4/21 (19%), iCBR=7/21 (33%). The 6-month PFS was 24%; 6-month iPFS, 33%. The PFS for patients (N=7) with iRECIST clinical benefit were 57, 52, 18, 15, 13, 7, and 7 months. The 6-month OS was 76%; the median OS, was 15.8 months. The most common toxicities were fatigue (62%) and rash (38%), and the most common grade 3/4 immune-related adverse events were hepatic dysfunction (9.5%) and adrenal insufficiency (9.5%). Treatment-related adverse events leading to discontinuation of therapy in four patients (21%). There were no grade 5 adverse events. CONCLUSIONS: Ipilimumab plus nivolumab is active in refractory metastatic adrenocortical cancer meeting the primary endpoint of the study, with a 19% iORR and 33% iCBR (includes SD/iSD>6 months) and with the longest PFS/iPFS of 52 and 57 months. TRIAL REGISTRATION NUMBER: NCT02834013 (registered 15 July, 2016; https://clinicaltrials.gov/ct2/show/NCT02834013).","journal":"Journal for ImmunoTherapy of Cancer","year":2024,"id":435585,"datarank":0.5027518066044006,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.11800940298517004,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.11800940298517004,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":11,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6284,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02834013"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":383952,"name":"Megan Othus","orcid":"0000-0001-8176-6371","position":1,"is_corresponding":false},{"id":251015,"name":"Young Kwang Chae","orcid":"0000-0003-1557-7235","position":2,"is_corresponding":false},{"id":724181,"name":"Tridu R. Huynh","orcid":"0000-0002-7945-2792","position":3,"is_corresponding":false},{"id":567087,"name":"Benjamin Tan","orcid":"0000-0003-1838-1182","position":4,"is_corresponding":false},{"id":658967,"name":"Timothy M. Kuzel","orcid":"0000-0002-7523-2397","position":5,"is_corresponding":false},{"id":1167413,"name":"Christine M. McLeod","orcid":null,"position":6,"is_corresponding":false},{"id":1046727,"name":"G. López","orcid":"0009-0005-4174-9071","position":7,"is_corresponding":false},{"id":290358,"name":"Helen X. Chen","orcid":null,"position":8,"is_corresponding":false},{"id":262226,"name":"Elad Sharon","orcid":"0000-0002-0044-9719","position":9,"is_corresponding":false},{"id":262227,"name":"Howard Streicher","orcid":"0000-0003-3683-9804","position":10,"is_corresponding":false},{"id":1243180,"name":"Christopher W. Ryan","orcid":"0000-0002-6941-9366","position":11,"is_corresponding":false},{"id":269619,"name":"Charles D. Blanke","orcid":null,"position":12,"is_corresponding":false},{"id":108759,"name":"Razelle Kurzrock","orcid":"0000-0003-4110-1214","position":13,"is_corresponding":false},{"id":110451,"name":"Sandip Pravin Patel","orcid":"0000-0002-8387-4840","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T02:00:08.103086Z","pmid":"39067873","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":[]}