Cancer cell · 2025
Phase 1/2 trial of encorafenib, cetuximab, and nivolumab in microsatellite stable BRAFV600E metastatic colorectal cancer.
СтатьяКлиническое исследование II фазыКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
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Morris Van K, Parseghian Christine M, Bahrambeigi Vahid, Abdelfattah Nourhan, Xiao Lianchun, Agrawal Anjali, Lin Kangyu, Raghav Kanwal P S, Wolff Robert A, Dasari Arvind, Huey Ryan W, Kee Bryan K, Overman Michael J, Willis Jason A, Le Phat H, Escano Michelle, Baig Yunyu C, Pan Kelsey, Menter David, Tam Alda L, Foo Wai C, Shen Li, Lee Hey Min, Gallup Thomas D, Margain Cori, Gallup Dave, Rajapakshe Kimal I, Guerrero Paola A, Wang Jing, Corcoran Ryan B, Maitra Anirban, Yun Kyuson, Kopetz Scott
Аннотация
The BRAF inhibitor encorafenib and anti-epidermal growth factor receptor (EGFR) antibody cetuximab modestly improve survival for patients with microsatellite stable (MSS) BRAFV600E metastatic colorectal cancer (mCRC), characterized by higher immune activation than MSS BRAFwild-type colorectal cancer (CRC). In this phase 1/2 study (NCT04017650) of 26 participants with MSS BRAFV600E mCRC who received encorafenib, cetuximab, and anti-PD-1 antibody nivolumab, we report an overall response rate of 50% (95% confidence interval [CI] 29-71) and median progression-free survival of 7.4 months (95% CI, 5.6-9.6). Transcriptomic profiling of pretreatment biopsies and extracellular vesicle RNA (evRNA) isolated from plasma show enrichment of non-canonical mitogen-activated protein kinase (MAPK) signaling and immune activation signatures for responders. Complement pathway activation enriches in non-responder biopsies. On serial evRNA profiling, decreased MAPK signature and increased interferon gamma response signature associate with sustained treatment benefit. MSS BRAFV600E mCRC with baseline MAPK activation and immune activation signatures may benefit from the triple combination but not with complement pathway activation.