{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T01:54:27Z","timestamp":1794534867339,"version":"4.9.1"},"reference-count":18,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"Importance<\/jats:title>Dysregulated metabolism is a hallmark of renal cell carcinoma (RCC). Glutaminase is a key enzyme that fuels tumor growth by converting glutamine to glutamate. Telaglenastat is an investigational, first-in-class, selective, oral glutaminase inhibitor that blocks glutamine utilization and downstream pathways. Preclinically, telaglenastat synergized with cabozantinib, a VEGFR2\/MET\/AXL inhibitor, in RCC models.<\/jats:p><\/jats:sec>Objective<\/jats:title>To compare the efficacy and safety of telaglenastat plus cabozantinib (Tela\u2009+\u2009Cabo) vs placebo plus cabozantinib (Pbo\u2009+\u2009Cabo).<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>CANTATA was a randomized, placebo-controlled, double-blind, pivotal trial conducted at sites in the US, Europe, Australia, and New Zealand. Eligible patients had metastatic clear-cell RCC following progression on 1 to 2 prior lines of therapy, including 1 or more antiangiogenic therapies or nivolumab plus ipilimumab. The data cutoff date was August 31, 2020. Data analysis was performed from December 2020 to February 2021.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Patients were randomized 1:1 to receive oral cabozantinib (60 mg daily) with either telaglenastat (800 mg twice daily) or placebo until disease progression or unacceptable toxicity.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary end point was progression-free survival (Response Evaluation Criteria in Solid Tumors version 1.1) assessed by blinded independent radiology review.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 444 patients were randomized: 221 to Tela\u2009+\u2009Cabo (median [range] age, 61 [21-81] years; 47 [21%] women and 174 [79%] men) and 223 to Pbo\u2009+\u2009Cabo (median [range] age, 62 [29-83] years; 68 [30%] women and 155 [70%] men). A total of 276 (62%) patients had received prior immune checkpoint inhibitors, including 128 with prior nivolumab plus ipilimumab, 93 of whom had not received prior antiangiogenic therapy. Median progression-free survival was 9.2 months for Tela\u2009+\u2009Cabo vs 9.3 months for Pbo\u2009+\u2009Cabo (HR, 0.94; 95% CI, 0.74-1.21; P<\/jats:italic>\u2009=\u2009.65). Overall response rates were 31% (69 of 221) with Tela\u2009+\u2009Cabo vs 28% (62 of 223) with Pbo\u2009+\u2009Cabo. Treatment-emergent adverse event (TEAE) rates were similar between arms. Grade 3 to 4 TEAEs occurred in 160 patients (71%) with Tela\u2009+\u2009Cabo and 172 patients (79%) with Pbo\u2009+\u2009Cabo and included hypertension (38 patients [17%] vs 40 patients [18%]) and diarrhea (34 patients [15%] vs 29 patients [13%]). Cabozantinib was discontinued due to AEs in 23 patients (10%) receiving Tela\u2009+\u2009Cabo and 33 patients (15%) receiving Pbo\u2009+\u2009Cabo.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this randomized clinical trial, telaglenastat did not improve the efficacy of cabozantinib in metastatic RCC. Tela\u2009+\u2009Cabo was well tolerated with AEs consistent with the known risks of both agents.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT03428217<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2022.3511","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T15:33:49Z","timestamp":1662046429000},"page":"1411","source":"Crossref","is-referenced-by-count":168,"title":["Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma"],"prefix":"10.1001","volume":"8","author":[{"given":"Nizar M.","family":"Tannir","sequence":"first","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camillo","family":"Porta","sequence":"additional","affiliation":[{"name":"University of Pavia, Pavia, Italy"},{"name":"Now with University of Bari Aldo Moro, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola J.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Auckland District Health Board and The University of Auckland, Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Motzer","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"McGregor","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit K.","family":"Jain","sequence":"additional","affiliation":[{"name":"H. 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