JCO precision oncology · 2026
Cobimetinib + Vemurafenib in Patients With BRAF V600E-Mutant Papillary Thyroid and Biliary Tract Cancers: Results From the TAPUR Study.
СтатьяКлиническое исследование II фазыНазвание и аннотация: Перевод пока не подготовлен
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Diamond-Rossi Samantha A, Rothe Michael, Garrett-Mayer Elizabeth, Pisick Evan, Bleeker Jonathan, Ganti Apar Kishor, Meric-Bernstam Funda, Moyers Justin T, Nair Suresh G, Kadakia Kunal C, Rohatgi Nitin, Sahai Vaibhav, Vijayvergia Namrata, Gold Philip J, Sharma Manish R, Hinshaw Dominique C, Gregory Abigail, Grantham Gina N, Halabi Susan, Schilsky Richard L
Аннотация
PURPOSE: TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations. Results of two cohorts of patients with advanced thyroid (TC) or biliary tract cancer (BTC) with BRAF V600E mutations treated with cobimetinib plus vemurafenib (C + V) are reported.
METHODS: Eligible patients had measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration. Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). Both cohorts expanded to stage II but closed before reaching the target sample size by pharmaceutical company request; inferences are based on thresholds set forth in the protocol to maintain the α level. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of SD, and safety.
RESULTS: Patients with TC (N = 22; n = 16 evaluable) or BTC (N = 18; n = 15 evaluable) with BRAF V600E mutations were enrolled. In the TC cohort, the DC and OR rates were 94% (one-sided 90% CI, 78 to 100) and 63% (95% CI, 35 to 85), respectively. In the BTC cohort, the DC and OR rates were 67% (one-sided 90% CI, 47 to 100) and 53% (95% CI, 27 to 79), respectively. The null hypothesis of 15% DC rate was rejected for both cohorts (P < .0001). Twenty-one patients (53%) had ≥1 treatment-related grade 3 to 4 adverse event (AE) or serious AE.
CONCLUSION: The combination of C + V met the prespecified criteria to declare a signal of activity in patients with TC and BTC with BRAF V600E mutations.
METHODS: Eligible patients had measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration. Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). Both cohorts expanded to stage II but closed before reaching the target sample size by pharmaceutical company request; inferences are based on thresholds set forth in the protocol to maintain the α level. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of SD, and safety.
RESULTS: Patients with TC (N = 22; n = 16 evaluable) or BTC (N = 18; n = 15 evaluable) with BRAF V600E mutations were enrolled. In the TC cohort, the DC and OR rates were 94% (one-sided 90% CI, 78 to 100) and 63% (95% CI, 35 to 85), respectively. In the BTC cohort, the DC and OR rates were 67% (one-sided 90% CI, 47 to 100) and 53% (95% CI, 27 to 79), respectively. The null hypothesis of 15% DC rate was rejected for both cohorts (P < .0001). Twenty-one patients (53%) had ≥1 treatment-related grade 3 to 4 adverse event (AE) or serious AE.
CONCLUSION: The combination of C + V met the prespecified criteria to declare a signal of activity in patients with TC and BTC with BRAF V600E mutations.