VS-6766

Dual RAF/MEK inhibitor VS 6766 for treatment of KRAS mutant NSCLC: Novel combinations targeting G12V or G12C variants

Jonathan Pachter, PhD, Chief Scientific Officer

NSCLC Drug Development Summit, July 14, 2021

FRAME: A phase I trial of the combination of the dual RAF-MEK inhibitor VS-6766 and the FAK inhibitor Defactinib; Evaluation of efficacy in KRAS mutated NSCLC.

Matthew G. Krebs, Rajiv Shinde, Rozana Abdul Rahman, Rafael Grochot, Martin Little, Jenny King, Mark Van De Velde, Joseph Kitchin, Mona Parmar, Alison Turner, Muneeb Mahmud, Christina Yap, Nina Tunariu, Juanita Lopez, Johann S. de Bono, Udai Banerji, Anna Minchom

AACR Virtual Annual Meeting-April 10-15 2021 & May 17-21 2021

Dual RAF/MEK Inhibitor VS-6766 Enhances Anti-Tumor Efficacy of KRAS G12C Inhibitors through a Vertical Pathway Inhibition Strategy

Silvia Coma, Sanjib Chowdhury, Jonathan A Pachter

AACR Virtual Annual Meeting-April 10-15 2021 & May 17-21 2021

Synergistic Antitumor Efficacy of the Dual RAF/MEK Inhibitor VS-6766 with FAK inhibition for Treatment of RAS-Dependent Solid Tumors

Silvia Coma, Monica Musteanu, Justine S. Paradis, J. Silvio Gutkind, Mariano Barbacid, Jonathan A. Pachter

AACR Virtual Annual Meeting-April 10-15 2021 & May 17-21 2021

Synergistic combinations with the novel dual RAF/MEK inhibitor VS-6766: Establishing VS-6766 as the backbone of therapy for RAS-driven cancers

Silvia Coma, Sanjib Chowdhury, Jonathan A. Pachter

RAS-Targeted Drug Discovery Summit – February 23-25, 2021

Synthetic Lethal Screens Reveal Co-Targeting FAK and MEK as a Multimodal Precision Therapy for GNAQ-Driven Uveal Melanoma

Justine S. Paradis, Monica Acosta, Robert Saddawi-Konefka, Ayush Kishore, Frederico Gomes, Nadia Arang, Manoela Tiago, Silvia Coma, Simone Lubrano, Xingyu Wu, Kyle Ford, Chi-Ping Day, Glenn Merlino, Prashant Mali, Jonathan A. Pachter, Takami Sato, Andrew E. Aplin, J. Silvio Gutkind

Clinical Cancer Research. 2021 February 10; DOI: 10.1158/1078-0432.CCR-20-3363

Intermittent schedules of the oral RAF–MEK inhibitor CH5126766/VS-6766 in patients with RAS/RAF-mutant solid tumours and multiple myeloma: a single-centre, open-label, phase 1 dose-escalation and basket dose-expansion study

Christina Guo, Maxime Chénard-Poirier, Desamparados Roda, Maria de Miguel, Samuel J Harris, Irene Moreno Candilejo, Priya Sriskandarajah, Wen Xu, Mariana Scaranti, Anastasia Constantinidou, Jenny King, Mona Parmar, Alison J Turner, Suzanne Carreira, Ruth Riisnaes, Laura Finneran, Emma Hall, Yuji Ishikawa, Kiyohiko Nakai, Nina Tunariu, Bristi Basu, Martin Kaiser, Juanita Suzanne Lopez, Anna Minchom, Johann S de Bono, Udai Banerji

Lancet Oncology. 2020 October 28; 21 (11): 1478–1488. DOI: 10.1016/S1470-2045(20)30464-2

Synergistic Combinations with the Dual RAF/MEK Inhibitor VS-6766 to Overcome Resistance Mechanisms

Jonathan Pachter, PhD

RAS-Targeted Drug Development September 16, 2020

Phase I study of the combination of a RAF-MEK inhibitor CH5126766 and FAK inhibitor defactinib in an intermittent dosing schedule with expansions in KRAS mutant cancers

Rajiv Shinde, Angelika Terbuch, Martin Little, Reece Caldwell, Roopa Kurup, Ruth Riisnaes, Mateus Crespo, Ruth Ruddle, Bora Gurel, Adam Stewart, Jenny King, Mona Parmar, Alison Turner, Florence Raynaud, Muneeb Mahmud, Christina Yap, Jonathan A. Pachter, Gordon B. Mills, Anna Minchom, Juanita Lopez, Susana N. Banerjee, Johann S. de Bono, Matthew Krebs, Udai Banerji

AACR Session I April 24-49 2020 Session II June 22-24 2020

Defactinib

Targeting FAK in anticancer combination therapies

John C. Dawson, Alan Serrels, Dwayne G. Stupack, David D. Schlaepfer & Margaret C. Frame

Nature Reviews Cancer. 2021 March 17; doi.org/10.1038/s41568-021-00340-6

Phase I Study of Defactinib combined with Pembrolizumab and Gemcitabine in Patients with Advanced Cancer: Experiences of Pancreatic Ductal Adenocarcinoma (PDAC) Patients

Andrea Wang-Gillam, Robert McWilliams, A. Craig Lockhart, Benjamin R. Tan Jr., Rama Suresh, Kian-Huat Lim, Katrina S. Pedersen,  Nikolaos Trikalinos, Olivia Aranha, Haeseong Park, Lee Ratner, Nicholas Boice, David G DeNardo.

AACR Session I April 24-49 2020 Session II June 22-24 2020

A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors

Suzanne F Jones, Lillian L Siu, Johanna C Bendell, James M Cleary, Albiruni R A Razak, Jeffrey R Infante, Shuchi S Pandya, Philippe L Bedard, Kristen J Pierce, Brett Houk, W Gregory Roberts, S Martin Shreeve, Geoffrey I Shapiro

Invest New Drugs. 2015 Oct;33(5):1100-7. doi: 10.1007/s10637-015-0282-y.