Presented today at the ESMO Congress 2024* by Maria Vieito, Medical Oncologist at the Vall d’Hebron University Hospital, CORE Phase I Investigator of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – Caixa Research and Clinical Investigator of VHIO’s Early Clinical Drug Development Group, preliminary results of the ongoing first-in-human, multicenter phase 1/2 clinical trial show preliminary efficacy of the novel CFT1946 oral BiDAC™ designed to selectively inhibit the BRAF V600 protein and overcome treatment resistance.
BRAF alterations are found in between 7 and 15% of cancers. BRAF V600 is one of the most frequently occurring mutations and associates with an increased proliferation rate of cancer cells.
“While approved selective inhibitors targeting BRAF alterations, particularly the BRAF V600 protein, are used in the treatment of some patients with BRAF-mutant solid tumors, their efficacy is limited due to intrinsic or acquired resistance to therapy,” said Maria Vieito, first author of this present study. “CTF1946 has been developed to overcome the limitations of classical BRAF inhibitors. This novel compound has been shown to degrade the BRAF V600 mutant protein and overcome RAF-driven resistance in preclinical models.”
First results of this phase 1/2 dose-escalation and cohort expansion clinical trial show the initial safety, tolerability, and early evidence of efficacy of CFT1946 monotherapy in previously treated patients with refractory BRAF-V600 mutant solid tumors.
As of April 12, 2024, 25 patients with melanoma, non-small cell lung cancer, colorectal cancer, or other solid tumor types had received treatment with CFT1946 monotherapy. All patients presented with a BRAF V600 mutation, and 24 patients had progressed after prior treatment with BRAF inhibitors.
“The top priority when evaluating a novel agent for the first time in people is safety. Initial results from this study show that CTF1946 monotherapy was well tolerated over the range of doses tested. We also observed BRAF V600E degradation in plasma and tissue samples,” added Vieito.
Regarding antitumor efficacy, partial responses and stable disease were observed in 9 patients. Notably, at a higher dose, partial responses of two patients showed a reduction of 64% and 54% in target lesions, respectively.
“These data are very preliminary but show promise as we continue to advance research into this type of therapy designed to target a specific mutation and prevent the acquisition of cancer drug resistance,” concluded Maria Vieito.
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*Session details
European Society for Medical Oncology Congress 2024, 13-17 September, Barcelona, Spain
Proffered paper session 1: Developmental therapeutics
Date: Fri, 13.09.2024
Time: 16:00h – 17:30h
Chairs: Elena Garralda (Barcelona, Spain), Lillian L. Siu (Toronto, Canada, Ontario)
612O – Preliminary results from a phase I study of CFT1946, a novel BIDAC degrader in mutant BRAF V600 solid tumors
Speaker: Maria Vieito (Barcelona, Spain)
Lecture Time: 16:10 – 16:20
