Combined PD-1, BRAF and MEK inhibition in BRAFV600E colorectal cancer: a phase 2 trial
Harvard University · Massachusetts General Hospital · +7 more institutions
Abstract
Abstract While BRAF inhibitor combinations with EGFR and/or MEK inhibitors have improved clinical efficacy in BRAF V600E colorectal cancer (CRC), response rates remain low and lack durability. Preclinical data suggest that BRAF/MAPK pathway inhibition may augment the tumor immune response. We performed a proof-of-concept single-arm phase 2 clinical trial of combined PD-1, BRAF and MEK inhibition with sparatlizumab (PDR001), dabrafenib and trametinib in 37 patients with BRAF V600E CRC. The primary end point was overall response rate, and the secondary end points were progression-free survival, disease control rate, duration of response and overall survival. The study met its primary end point with a confirmed…
Citation impact
- FWCI
- 39.73
- Percentile
- 100%
- References
- 54
Authors
45- JTJun TianCorresponding
Harvard University, Massachusetts General Hospital
- JCJonathan Chen
Broad Institute, Harvard University, Massachusetts General Hospital, Massachusetts Institute of Technology
- SCSherry Chao
Broad Institute, Massachusetts Institute of Technology
- KPKarin Pelka
Broad Institute, Gladstone Institutes, Massachusetts Institute of Technology
- MGMarios Giannakis
Harvard University, Dana-Farber Cancer Institute
Topics & keywords
- Dabrafenib
- Trametinib
- Colorectal cancer
- Medicine
- MAPK/ERK pathway
- MEK inhibitor
- Immune system
- Oncology
- Good health and well-being
Funding
- AAAmerican Association for Cancer ResearchAward: SU2C-AACR-DT22-17
- MGMassachusetts General Hospital
- EIEntertainment Industry Foundation
- SFSociety for Immunotherapy of Cancer
- DFDeutsche Forschungsgemeinschaft
- NINational Institutes of HealthAwards: NCI R01, U54CA224068, R01 CA208756, P50 CA127003, T32CA207021
- SUStand Up To CancerAwards: DT22-17, SU2C-AACR-DT22-17
- NCNational Cancer InstituteAwards: T32CA207021, CA127003, P50 CA127003, U54CA224068
- MRMoonshot Research and Development Program