Reference Detail

Ref Type

Abstract

PMID

Authors

T.W. Kim J. Lee S.J. Shin S-W. Han Y.J. Kim J-S. Kim S.Y. Oh D.H. Lee M.H. Kim S.T. Kim Y. Hong S. Kim T. Kim B. Lee J. Eng-Wong Y. Yan C. Chou Y.S. Noh

Title

661MO Anti-tumor activity of belvarafenib in combination with cobimetinib in patients with metastatic solid tumors harboring BRAF fusions or BRAF class II/III mutation

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	34	Supplement 2	October 2023	S465	Ann Oncol

URL

https://www.annalsofoncology.org/article/S0923-7534(23)02684-4/fulltext

Abstract Text

Background Belvarafenib (Belva) is a type II selective RAF dimer inhibitor that, in combination with Cobimetinib (Cobi) has shown clinical activity in patients with NRAS-mutant melanoma ( ASCO 2021 , ESMO 2021 ). One cohort in this phase I trial evaluated BRAF fusions (including indel/rearrangement) or class II/III point mutations, which are considered potential therapeutic targets for Belva +/- Cobi. Here, we present findings on activity and safety of Belva and Cobi in patients with BRAF fusion including indel/rearrangement. Methods A total of 23 patients harboring BRAF non-canonical aberration were enrolled and treated with Belva 300mg PO BID and Cobi 20mg PO TIW (3 times a week) in the HM-RAFI-103 study (NCT03284502). Sub-cohort A (SC-A) enrolled patients with BRAF fusions and sub-cohort B (SC-B) enrolled patients with BRAF class II/III point mutations. Safety results were updated based on 133 patients who were treated with Belva and Cobi as of Jan 31, 2023. Results In SC-A, a total of 15 patients harboring BRAF fusions (Melanoma (10), NSCLC (3), CRC (1), Pancreatic cancer (1)) and 8 patients with BRAF class II/III point mutation were in SC-B (Biliary tract cancer (3), CRC (3), SCLC (1), Glioblastoma (1)) were enrolled. The confirmed objective response rate (ORR), assessed by investigators’ assessment, for SC-A was 60.0%, median progression-free survival (mPFS) was 13.7 months, and median duration of response was 12.0 months (95% CI: 7.43 to 22.34) with median follow-up time 12.9 months, while patients in SC-B showed best response of stable disease. As of cut-off date, the most common treatment related adverse events from 133 patients is dermatitis acneiform (54.1%), rash (28.6%), and blood creatine phosphokinase increased (24.1%). No new safety signals were found. Conclusions The combination of Belva with Cobi showed promising anti-tumor activity as well as durable responses in patients with BRAF fusions regardless of cancer type.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF fusion	Advanced Solid Tumor	predicted - sensitive	Belvarafenib + Cobimetinib	Phase I	Actionable	In a Phase I trial (HM-RAFI-103), Belvarafenib (HM95573) and Cotellic (cobimetinib) combination therapy demonstrated preliminary activity in patients with advanced solid tumors harboring BRAF fusions, resulting in an objective response rate of 60% (9/15, all partial responses), a disease control rate of 93.3% (14/15), with a median progression-free survival of 13.7 months, and a median duration of response of 12 months (Ann Oncol 34 (2023): S465; NCT03284502).	detail...