SPY312.23+1.71 0.55%
DIA258.42+1.11 0.43%
IXIC10,207.63+53.00 0.52%

Verastem Oncology Highlights Presentation Of Preclinical Data Supporting Combo Of VS-6766, Defactinib In Metastatic Uveal Melanoma

Verastem, Inc. (NASDAQ:VSTM) (also known as Verastem Oncology), a biopharmaceutical company committed to developing and commercializing new medicines for patients battling cancer, today announced results from a study

Benzinga · -

Verastem, Inc. (NASDAQ:VSTM) (also known as Verastem Oncology), a biopharmaceutical company committed to developing and commercializing new medicines for patients battling cancer, today announced results from a study that provides preclinical proof-of-concept for combining VS-6766, its RAF/MEK inhibitor, with defactinib, its focal adhesion kinase (FAK) inhibitor, for the treatment of metastatic uveal melanoma (UM), the most prevalent eye cancer among adults. The data comprise one of four virtual posters with Verastem authors being presented today at the American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting II, which is taking place June 22-24, 2020.

Uveal melanoma arises from the melanin-producing cells in the eye, similar to how it arises in cutaneous melanoma. While it’s considered rare, primary UM metastasizes in 50% of patients with only 8% of patients surviving 2 years after development of metastatic disease.1 Previously, MEK inhibitors, including selumetinib and trametinib, have failed to show substantial clinical benefit for patients with metastatic uveal melanoma.2,3 Indeed, no current therapies improve overall survival for metastatic UM and there is a high unmet need for novel therapies.4

In the current preclinical study, FAK inhibition (FAKi; e.g., defactinib) demonstrated synergistic growth-inhibitory effects in UM cells when combined with a MEK inhibitor (MEKi) or the investigational RAF/MEK inhibitor VS-6766. Additionally, MEKi increased phosphorylation of FAK, suggesting the need for FAK blockade in combination with MEKi for more complete antitumor effect. Accordingly, FAKi combination with MEKi induced apoptotic cell death leading to rapid tumor regression in UM xenografts, whereas the MEKi or FAKi as single agents showed tumor growth inhibition but failed to showed tumor shrinkage. Furthermore, the FAKi/MEKi combination was successful at reducing tumor burden in liver metastasis UM models.

“The study identified and reinforced FAK as a viable pathway to inhibit downstream from the GNAQ pathway, which is constitutively active in UM,” said J. Silvio Gutkind, PhD, Distinguished Professor of Pharmacology and Associate Director for Basic Science at UC San Diego Moores Cancer Center, and senior investigator of the study. “We observed that co-targeting of FAK and RAF/MEK signaling led to tumor collapse in UM xenograft and liver metastasis models in vivo. Based on the encouraging results of this study, we are excited to work toward clinical testing of defactinib with VS-6766 for patients with metastatic uveal melanoma.”

“These data build on a growing body of evidence that underscore the potential of the VS-6766/defactinib combination for treatment of a variety of solid tumors with significant medical need,” said Brian Stuglik, Chief Executive Officer of Verastem Oncology. “We will continue to evaluate the combination in metastatic uveal melanoma along with rapidly advancing our broader clinical development program in solid tumors.”

The combination of VS-6766 and defactinib is being evaluated in patients with Low Grade Serous Ovarian Cancer (LGSOC), and KRAS mutant non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) in the ongoing investigator-initiated Phase I trial. The company also plans to support a Phase II investigator-initiated study of the combination of VS-6766 and defactinib in uveal melanoma anticipated to begin in late 2020.

Details for all abstracts selected for presentation at the AACR 2020 Virtual Meeting II are as follows:

Title: FAK and MEK co-targeting: A new multimodal precision therapy for GNAQ-driven uveal melanoma
Lead author: Justine S. Paradis
Poster #: 6406/30
Session: PO.ET06.05
Date and Time: Monday, June 22, 2020; 9:00 a.m. to 6:00 p.m. EDT
URL: https://www.abstractsonline.com/pp8/#!/9045/presentation/5323

Title: The dual PI3K-δ/PI3K-γ inhibitor duvelisib inhibits signaling and proliferation of solid tumor cells expressing PI3K-δ and/or PI3K-γ
Lead author: Silvia Coma
Poster #: 663/10
Session: PO.ET06.06
Date and Time: Monday, June 22, 2020; 9:00 a.m. to 6:00 p.m. EDT
URL: https://www.abstractsonline.com/pp8/#!/9045/presentation/1880

Title: Single cell expression analysis of PIK3 genes to direct solid tumor treatment with the dual PI3K-δ,γ inhibitor duvelisib
Lead author: Samantha Hidy
Poster #: 1552/3
Session: PO.TB06.02
Date and Time: Monday, June 22, 2020; 9:00 a.m. to 6:00 p.m. EDT
URL: https://www.abstractsonline.com/pp8/#!/9045/presentation/7806

Title: PEGylated recombinant human hyaluronidase, PEGPH20, significantly enhances the anti-tumor activity of the combination of focal adhesion kinase Inhibitor and anti-PD-1 antibody by targeting CXCR4-expressing myeloid cells in a murine model of PDAC
Lead author: Arsen Osipov
Poster #: 1588/9
Session: PO.TB06.04
Date and Time: Monday, June 22, 2020; 9:00 a.m. to 6:00 p.m. EDT
URL: https://www.abstractsonline.com/pp8/#!/9045/presentation/7864