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Ref Type abstract
PMID
Authors F.P. Lin, A. Mersiades, J. Lee, W. Xu, S. Chinchen, M. Charakidis, S. Thavaneswaran, B.G.M. Hughes, C.R. Underhill, H.S. Takhar, R. Harrup, A. Nagrial, M. Millward, J. Desai, D. Espinoza, C.K. Lee, B.J. Solomon, J. Simes, N. Pavlakis, D. Thomas
Title 623P Phase II trial of vemurafenib (VEM) and cobimetinib (COB) in BRAF V600-mutated solid tumours and first-line (1L) non-small cell lung cancer (NSCLC): Australian molecular screening and therapeutics (MoST) substudy 12
Journal Vol Issue Date Pages Journal Short Title
Annals of Oncology 35 Supplement 2 September 2024
URL https://www.annalsofoncology.org/article/S0923-7534(24)02209-9/fulltext
Abstract Text Background Class I BRAF mutations contribute to the oncogenesis of 4% of solid tumours and 3% of non-squamous NSCLC. While combined BRAF/MEK inhibition with VEM+COB has been established in melanoma management, its activity in other tumour types and 1L NSCLC treatment remains underexplored. Methods This multicentre phase 2 trial (ACTRN12620000861954), part of the MoST program and its NSCLC subprogram (ASPiRATION), assessed the activity of the VEM+COB in 2 patient (pt) groups with advanced BRAF V600 mutant cancers (refractory solid tumours and 1L NSCLC) identified through comprehensive genomic profiling. Pts received VEM 960 mg twice daily and COB 60 mg daily (days 1 to 21 every 28 days) until disease progression, withdrawal, or unacceptable toxicity. The primary objective was objective response rate (ORR) assessed by RECIST v1.1 or RANO criteria (primary brain tumours). Secondary objectives included overall and progression-free survival (OS and PFS), PFS rate at 6 months (mo), safety and tolerability. The activity threshold was defined as > 6 responses in 32 pts preplanned for each group; the Kaplan-Meier method was used for time-to-event analyses. Results This study enrolled 64 pts (36 solid, 28 1L NSCLC) with median follow-up of 13.1 and 14.7 mo, respectively (solid and 1L NSCLC groups). Both groups met the predefined threshold, achieving ORR of 50% (18 of 36, solid) and 42% (10 of 24 RECIST evaluable, 1L NSCLC). Confirmed responses were seen in 16 pts with NSCLC (across both groups, including 1 complete, CR), 2 each with biliary tract, unknown primary, salivary gland (1 CR), and papillary thyroid cancers, 1 each with glioblastoma, anal, pancreatic acinar carcinoma, and a malignant peripheral nerve sheath tumour. In the solid group, the median PFS and OS were 7.9 mo (95% CI: 5.6–15.9) and 15.9 mo (9.1–21.9). The 6-mo PFS rates were 68% (48–82%) and 67% (45–81%) for the solid and 1L NSCLC groups respectively. Ten pts (16%) discontinued treatment and 21 pts (33%) required dose adjustments due to adverse events. Conclusions VEM+COB is active in a range of advanced solid tumours and 1L NSCLC with a BRAF V600 mutation.

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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 V600X Advanced Solid Tumor predicted - sensitive Cobimetinib + Vemurafenib Phase II Actionable In a Phase II trial, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an objective response rate (ORR) of 50% (18/36), median progression-free survival of 7.9 months, and overall survival of 15.9 months in patients with advanced solid tumors harboring a BRAF V600 mutation and an ORR of 42% (10/24) in treatment-naive patients with non-small cell lung cancer harboring a BRAF V600 mutation (Ann Oncol (2024) 35 (Suppl_2): S498). detail...
BRAF V600X lung non-small cell carcinoma predicted - sensitive Cobimetinib + Vemurafenib Phase II Actionable In a Phase II trial, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an objective response rate (ORR) of 50% (18/36), median progression-free survival of 7.9 months, and overall survival of 15.9 months in patients with advanced solid tumors harboring a BRAF V600 mutation and an ORR of 42% (10/24) in treatment-naive patients with non-small cell lung cancer harboring a BRAF V600 mutation (Ann Oncol (2024) 35 (Suppl_2): S498). detail...