Cobimetinib Plus Vemurafenib in Patients With Colorectal Cancer WithBRAFMutations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

• DOI: 10.1200/po.22.00191
• Publication Date: 2022-11-21T20:59:35Z
• Authors: Kelsey A. Klute; Michael Rothe; Elizabeth Garrett...; Pam K. Mangat; Reza Nazemzadeh; Kathleen J. Yost; Herbert L. Duvivier; Eugene R. Ahn; Timothy L. Cannon; Olatunji B. Alese; John C. Krauss; Ramya Thota; Carmen J. Calfa; Crystal S. Denlinger; Raegan O'Lone; Susan Halabi; Gina N. Grantham; Richard L. Schilsky
• Keywords: Clinical endpoint

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 known to be drug targets. The results cohort colorectal (CRC) BRAF mutations treated cobimetinib (C) plus vemurafenib (V) are reported. METHODS Eligible had CRC, no standard treatment options, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors V600E/D/K/R mutations, MAP2K1/2, MEK1/2, or NRAS mutations. C was taken 60 mg orally once daily for 21 days followed by seven off, V 960 twice daily. Simon's two-stage design used primary study end point objective response stable at least 16 weeks duration. Secondary points were progression-free survival, overall safety. RESULTS Thirty enrolled from August 2016 2018; all CRC V600E mutation except one patient K601E mutation. Three not evaluable efficacy. Eight partial responses six duration observed control rates 52% (95% CI, 35 65) 30% 14 50), respectively. null hypothesis 15% rate rejected ( P < .0001). Thirteen grade 3 adverse event serious possibly related + V: anemia, decreased lymphocytes, dyspnea, diarrhea, elevated liver enzymes, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, upper gastrointestinal hemorrhage. CONCLUSION combination has heavily pretreated