{"doi":"10.1210/clinem/dgae512","title":"Cabozantinib Plus Ipilimumab/Nivolumab in Patients With Previously Treated Advanced Differentiated Thyroid Cancer","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>This investigator-initiated phase II trial aimed to evaluate the efficacy of cabozantinib in combination with nivolumab and ipilimumab (CaboNivoIpi) in previously treated patients with radioactive iodine-refractory differentiated thyroid cancer.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>Eligible patients with radioactive iodine-refractory differentiated thyroid cancer who progressed on 1 prior line of vascular endothelial growth factor receptor-targeted therapy received a 2-week run-in of cabozantinib monotherapy followed by CaboNivoIpi for 4 cycles (cycle length = 6 weeks), followed by cabozantinib plus nivolumab (cycle length = 4 weeks) until disease progression. The primary endpoint was objective response rate (ORR) within the first 6 months of treatment. A Simon optimal 2-stage design allowed for an interim analysis after accrual of 10 evaluable patients. At least 5 responses were needed to proceed to stage 2.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>Among 11 patients enrolled, the median age was 69 years. Prior vascular endothelial growth factor receptor-targeted therapies included lenvatinib, pazopanib, and sorafenib plus everolimus. Median follow-up was 13.4 months. Among 10 evaluable patients, ORR within the first 6 months of treatment was 10% (1 partial response). Median progression-free survival was 9 months (95% CI, 3.0–not reached) and median overall survival was 19.2 months (95% CI, 4.6–not reached). Grade 3/4 treatment-related adverse events (AEs) were noted in 55% (6/11) and grade 5 AEs in 18% (2/11) of patients. The most common treatment-related AE was hypertension. The study did not reach its prespecified efficacy threshold.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>CaboNivoIpi had low ORRs and a high rate of grade ≥3 treatment-related AEs.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trial Registration</jats:title>\n                  <jats:p>NCT03914300</jats:p>\n               </jats:sec>","journal":"The Journal of Clinical Endocrinology &amp; Metabolism","year":2025,"id":609776,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1567454,"name":"Eric J Sherman","orcid":null,"position":1,"is_corresponding":false},{"id":449643,"name":"Erminia Massarelli","orcid":"0000-0001-7798-7286","position":2,"is_corresponding":false},{"id":1567455,"name":"Jorge Nieva","orcid":null,"position":3,"is_corresponding":false},{"id":809328,"name":"Jameel Muzaffar","orcid":"0000-0003-1924-2301","position":4,"is_corresponding":false},{"id":845106,"name":"John C Morris","orcid":null,"position":5,"is_corresponding":false},{"id":281801,"name":"Mabel Ryder","orcid":"0000-0002-0520-6505","position":6,"is_corresponding":false},{"id":1567456,"name":"Alan L Ho","orcid":null,"position":7,"is_corresponding":false},{"id":347150,"name":"Mark Agulnik","orcid":"0000-0003-3513-3519","position":8,"is_corresponding":false},{"id":693773,"name":"Lai Wei","orcid":"0000-0002-5936-797X","position":9,"is_corresponding":false},{"id":1463031,"name":"Demond Handley","orcid":"0000-0003-0223-1550","position":10,"is_corresponding":false},{"id":1567457,"name":"Catherine Moses","orcid":null,"position":11,"is_corresponding":false},{"id":1567458,"name":"Rajani Jacob","orcid":null,"position":12,"is_corresponding":false},{"id":25357,"name":"John Wright","orcid":"0000-0003-2683-4428","position":13,"is_corresponding":false},{"id":262227,"name":"Howard Streicher","orcid":"0000-0003-3683-9804","position":14,"is_corresponding":false},{"id":1026849,"name":"William Carson","orcid":"0000-0002-0321-5096","position":15,"is_corresponding":false},{"id":1567459,"name":"Manisha H Shah","orcid":null,"position":16,"is_corresponding":false},{"id":806761,"name":"Bhavana Konda","orcid":"0000-0002-9099-5990","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Cabozantinib Plus Ipilimumab/Nivolumab in Patients With Previously Treated Advanced Differentiated Thyroid Cancer","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>This investigator-initiated phase II trial aimed to evaluate the efficacy of cabozantinib in combination with nivolumab and ipilimumab (CaboNivoIpi) in previously treated patients with radioactive iodine-refractory differentiated thyroid cancer.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>Eligible patients with radioactive iodine-refractory differentiated thyroid cancer who progressed on 1 prior line of vascular endothelial growth factor receptor-targeted therapy received a 2-week run-in of cabozantinib monotherapy followed by CaboNivoIpi for 4 cycles (cycle length = 6 weeks), followed by cabozantinib plus nivolumab (cycle length = 4 weeks) until disease progression. The primary endpoint was objective response rate (ORR) within the first 6 months of treatment. A Simon optimal 2-stage design allowed for an interim analysis after accrual of 10 evaluable patients. At least 5 responses were needed to proceed to stage 2.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>Among 11 patients enrolled, the median age was 69 years. Prior vascular endothelial growth factor receptor-targeted therapies included lenvatinib, pazopanib, and sorafenib plus everolimus. Median follow-up was 13.4 months. Among 10 evaluable patients, ORR within the first 6 months of treatment was 10% (1 partial response). Median progression-free survival was 9 months (95% CI, 3.0–not reached) and median overall survival was 19.2 months (95% CI, 4.6–not reached). Grade 3/4 treatment-related adverse events (AEs) were noted in 55% (6/11) and grade 5 AEs in 18% (2/11) of patients. The most common treatment-related AE was hypertension. The study did not reach its prespecified efficacy threshold.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>CaboNivoIpi had low ORRs and a high rate of grade ≥3 treatment-related AEs.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trial Registration</jats:title>\n                  <jats:p>NCT03914300</jats:p>\n               </jats:sec>","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39133806","pmcid":"PMC11834700","openalex_id":"https://openalex.org/W4401558354","authors":[],"funders":[{"funder_name":"The Ohio State University Comprehensive Cancer Center","grant_id":"5UM1CA186712-03","title":null},{"funder_name":"Memorial Sloan Kettering","grant_id":"UM1CA186691","title":null},{"funder_name":"City of Hope Cancer Center","grant_id":"4UM1CA186717-07","title":null},{"funder_name":"University of Southern California","grant_id":"UM1CA186717","title":null},{"funder_name":"Moffitt Cancer Center","grant_id":"2UM1 CA186644-06","title":null},{"funder_name":"Mayo Clinic, Rochester","grant_id":"3UM1CA186686-03S1","title":null},{"funder_name":"NCI NIH HHS","grant_id":"UM1 CA186644","title":null},{"funder_name":"NCI NIH HHS","grant_id":"UM1 CA186686","title":null},{"funder_name":"NCI NIH HHS","grant_id":"UM1 CA186712","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA008748","title":null},{"funder_name":"National Cancer Institute","grant_id":"","title":null}],"total_grants":11,"fwci":2.3748,"citation_percentile":0.90335853,"influential_citations":0,"citation_trend":[{"year":2024,"count":2},{"year":2025,"count":7}],"oa_status":"green","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11834700","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11834700","host_type":"repository"},{"url":"https://academic.oup.com/jcem/advance-article-pdf/doi/10.1210/clinem/dgae512/58923487/dgae512.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jcem/article-pdf/110/3/830/58923487/dgae512.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1210/clinem/dgae512","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39133806","host_type":"repository"}],"fields_of_study":["Thyroid Cancer Diagnosis and Treatment","Thyroid Disorders and Treatments","Thyroid and Parathyroid Surgery","Humans","Female","Male","Aged","Middle Aged","Thyroid Neoplasms","Anilides","Pyridines","Ipilimumab","Antineoplastic Combined Chemotherapy Protocols","Nivolumab","Aged, 80 and over","Adult","Follow-Up Studies"],"mesh_terms":["Ipilimumab","Nivolumab","Adult","Aged","Aged, 80 and over","Anilides","Antineoplastic Combined Chemotherapy Protocols","Female","Follow-Up Studies","Humans","Male","Middle Aged","Pyridines","Thyroid Neoplasms"],"keywords":["Medicine","Cabozantinib","Nivolumab","Internal medicine","Pazopanib","Lenvatinib","Ipilimumab","Adverse effect","Interim analysis","Axitinib","Oncology","Sorafenib","Clinical endpoint","Refractory (planetary science)","Everolimus","Response Evaluation Criteria in Solid Tumors","Progressive disease","Rash","Discontinuation","Thyroid cancer","Cancer","Clinical trial","Phases of clinical research","Sunitinib","Chemotherapy","Hepatocellular carcinoma","Immunotherapy","VEGFR","Differentiated Thyroid Cancer","Immune Checkpoint Inhibitors"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T15:04:50.967234Z","pmid":null,"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":[]}