Phase II basket trial of Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: adrenocortical carcinoma cohort

• Published in: Journal for immunotherapy of cancer 2024-07, Vol.12 (7), p.e009074
• Main Authors: Patel, Sandip P, Othus, Megan, Chae, Young Kwang, Huynh, Tridu, Tan, Benjamin, Kuzel, Timothy, McLeod, Christine, Lopez, Gabby, Chen, Helen X, Sharon, Elad, Streicher, Howard, Ryan, Christopher W, Blanke, Charles, Kurzrock, Razelle
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Neoplasms - drug therapy; Adrenal Cortex Neoplasms - mortality; Adrenocortical Carcinoma - drug therapy; Adrenocortical Carcinoma - mortality; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer therapies; Clinical/Translational Cancer Immunotherapy; Combination therapy; CTLA-4 Antigen - antagonists & inhibitors; Female; Hormones; Humans; Hypotheses; Immune Checkpoint Inhibitor; Immune Checkpoint Inhibitors - administration & dosage; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immune modulatory; Immunotherapy; Ipilimumab - administration & dosage; Ipilimumab - adverse effects; Ipilimumab - therapeutic use; Male; Metastasis; Middle Aged; Neuroendocrine and Adrenal Tumor; Neuroendocrine tumors; Nivolumab - administration & dosage; Nivolumab - adverse effects; Nivolumab - therapeutic use; Pathology; Patients; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Prospective Studies; Short Report; Thyroid gland; Toxicity; Tumors
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2024-009074

ObjectivesMultiple 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/settingA 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.Participants21 eligible patients were registered. Median age was 53 years (range 26–69); 16 (76%) were women.InterventionsIpilimumab 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 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%.ResultsThe 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.ConclusionsIpilimumab plus nivolumab is active in refractory metastatic adrenocortical cancer meeting the primary endpoint of the study, with a 19% iORR and 33% iCBR (includes