A Phase 2 Study of Avutometinib (VS-6766) (Dual RAF/MEK Inhibitor) as a Single Agent and In Combination With Defactinib (FAK Inhibitor) in Recurrent KRAS-Mutant (KRAS-MT) and BRAF-Mutant (BRAF-MT) Non-Small Cell Lung Cancer (NSCLC) (RAMP 202)

This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy or VS-6766 in combination with defactinib in subjects with recurrent Non-small cell lung cancer.

Start Date31 Dec 2020

Sponsor / Collaborator

Verastem, Inc.

NCT03915951 / Active, not recruitingPhase 2

A Phase 2, Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer

This is an open-label, multicenter, non-randomized, Phase 2 study to determine the safety, tolerability and efficacy of encorafenib given in combination with binimetinib in patients with BRAFV600E-mutant metastatic non-small cell lung cancer (NSCLC). Patients who are either treatment-naïve, OR who have received 1) first-line treatment with standard platinum-based chemotherapy, OR 2) first-line treatment with an anti-programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) inhibitor given alone or in combination with platinum-based chemotherapy will be enrolled.

Start Date04 Jun 2019

Sponsor / Collaborator

Pfizer Inc.

NCT02974725 / TerminatedPhase 1

A Phase Ib, Open-label, Multicenter Study of Oral LXH254-centric Combinations in Adult Patients With Advanced or Metastatic KRAS or BRAF Mutant Non-Small Cell Lung Cancer or NRAS Mutant Melanoma

To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.

Start Date24 Feb 2017

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

100 Clinical Results associated with BRAF Mutation Non-small Cell Lung Cancer

100 Translational Medicine associated with BRAF Mutation Non-small Cell Lung Cancer

0 Patents (Medical) associated with BRAF Mutation Non-small Cell Lung Cancer

Literatures (Medical) associated with BRAF Mutation Non-small Cell Lung Cancer

01 Sep 2024·Anti-Cancer Drugs

MET alterations as resistance mechanisms of dabrafenib-trametinib in BRAF p.V600E mutated non-small cell lung cancer patient

Article

Author: Mazzaschi, Giulia ; Adorni, Alessia ; Minari, Roberta ; Gnetti, Letizia ; Lagrasta, Costanza Anna Maria ; Tiseo, Marcello ; Dodi, Alessandra ; Testi, Irene ; Airò, Giulia ; Pecci, Federica ; Azzoni, Cinzia ; Pluchino, Monica ; Verzè, Michela

The combination of BRAF and MEK inhibitors demonstrated significant clinical benefit in patients with BRAF-mutant non-small cell lung cancer (NSCLC). However, the molecular mechanisms of acquired resistance to BRAF and MEK inhibition in NSCLC are still unknown. Herein, we report a case of a 76-year-old man with a history of smoking who was diagnosed with BRAF V600E-mutant lung adenocarcinoma (PD-L1 > 50%) and subsequently candidate to first-line therapy with pembrolizumab. After 18 months since the start of immunotherapy, computed tomography scan showed disease progression and a second-line therapy with dabrafenib and trametinib was initiated. Seven months later, due to a suspect disease progression, a left supraclavicular lymphadenectomy was performed and next-generation sequencing analysis revealed the appearance of MET exon 14 skipping mutation, while fluorescence in situ hybridization analysis showed MET amplification. The patient is still on BRAF and MEK inhibitor treatment. Our case highlights the relevance of performing tumor tissue rebiopsy at the time of progression during treatment with BRAF/MEK inhibition with the aim of identifying putative mechanisms of resistance.

29 Jul 2024·Future Oncology

Dabrafenib-trametinib in BRAF V600-mutated non-small-cell lung cancer: a single center real world experience

Article

Author: Carrozzi, Laura ; Massa, Valentina ; Sbrana, Andrea ; Chella, Antonio ; Bernardini, Laura ; Petrini, Iacopo ; Cappelli, Sabrina

Aim: We retrospectively evaluated the effect of dabrafenib/trametinib combination in patients with BRAF-mutated non-small-cell lung cancer (NSCLC) treated in a single center from 2017 to 2022.Patients: The response and safety data of 42 patients (27 treated in first-line and 15 as second/subsequent lines) were analyzed.Results: The objective response was 73.8%, with no differences between patients undergoing first- or second-line. A longer, statistically significant median progression-free survival (PFS) was observed in patients receiving the combination in first-line vs those in the second/subsequent lines (19.9 months [95% CI: 19.7-20] vs 13.1 months [95% CI: 8.6-17.6], respectively; p = 0.012). The median overall survival (OS) was 29.9 months (95% CI: 14.1-45.7) for patients treated with the combination in first-line and 22.4 months (95% CI: 14.6-30.2) for those treated in subsequent lines. The combination was well toleratedConclusion: We confirm the efficacy of dabrafenib/trametinib in BRAF-V600-mutated NSCLC.

01 Apr 2024·Translational Lung Cancer Research

The evolving treatment landscape for BRAF-mutated non-small cell lung cancer

Communications

Author: Rose, April A N ; Dankner, Matthew ; Maxwell, Jennifer

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