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Verastem Oncology Announces New Data Published in The Lancet Oncology Supports Potential of VS-6766 as Treatment for RAS Mutant Tumors
Investigator-Initiated Phase 1 Study is First to Evaluate a Dual RAF/MEK Inhibitor Using Innovative Intermittent Dosing Schedules in Patients Harboring RAS/RAF Pathway Mutations
Study Finds VS-6766 Regimen is Tolerable and Shows Antitumor Activity in Recommended Phase 2 Single Agent Dose
Phase 2 Registration-Directed Trials with VS-6766 Alone and in Combination with Defactinib in Low-Grade Serous Ovarian Cancer and KRAS Mutant Non-Small Cell Lung Cancer Expected to Commence by Year-End 2020
“The positive results observed with this innovative intermittent dosing regimen of VS-6766 demonstrate its significant potential across various cancers with RAS/RAF/MEK pathway mutations,” stated
The full manuscript, titled “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,” can be accessed here.
“These results support the potential of VS-6766 as a treatment for a variety of cancers where conventional approaches have been sub-optimal and there is significant unmet need. We believe VS-6766 has the potential to be the backbone of RAS therapy by addressing the multiple points of resistance and toxicity issues that have made advancing new options difficult,” said
Results from the Phase 1 Study Investigating Intermittent Dosing of VS-6766 in Patients with RAS/RAF-mutated Solid Tumors and Multiple Myeloma
Four mg twice weekly was established as the recommended Phase 2 dose for VS-6766 monotherapy and was deemed tolerable based on clinician’s assessment with several patients remaining on study for more than six months.
In the subsequent basket expansion part, seven (26.9%) of 26 response-evaluable patients with RAS mutations in the basket expansion achieved objective responses, with response rates in patients with NSCLC, gynecological malignancies, colorectal cancer (CRC), melanoma, and multiple myeloma being 3/10 (30%), 3/5 (60%), 0/4 (0%), 0/1 (0%), and 1/6 (16.7%), respectively. In all six responders with solid tumors, tumor shrinkage was observed at the time of the first restaging scan after two cycles of treatment, with partial responses confirmed after two to four cycles. Five of the six responses lasted more than six months.
Among the 57 safety-evaluable patients, the most common Grade 3/4 treatment related adverse events (TRAEs) were rash (19%), CPK elevation (11%), hypoalbuminemia (11%), and fatigue (7%). Five (9%) patients experienced treatment-related serious adverse events. In the study, TRAEs were manageable, resolved spontaneously or reversed with dose modification. There were no treatment-related deaths. The study also confirmed a long half-life of 55 hours and target engagement in the form of reduction of both p-ERK and p-MEK in three patients who underwent paired biopsies, supporting intermittent dosing schedules.
This study was supported by Chugai Pharmaceutical Co., Ltd.
VS-6766 (formerly known as CH5126766 and CKI27) is a unique inhibitor of the RAF/MEK signaling pathway. In contrast to other MEK inhibitors in development, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors.
Defactinib (VS-6063) is an oral small molecule inhibitor of FAK and PYK2 that is currently being evaluated as a potential combination therapy for various solid tumors. The Company has received Orphan Drug designation for defactinib in ovarian cancer and mesothelioma in the US, EU and
About the VS-6766/Defactinib Combination
RAS mutant tumors are present in 30% of all human cancers and have historically presented a difficult treatment challenge and are often associated with significantly worse prognosis. Challenges associated with identifying new treatment options for these types of cancers include resistance to single agents, identifying tolerable combination regimens with MEK inhibitors and new RAS inhibitors in development addressing only a minority of all RAS mutated cancers.
The combination of VS-6766 and defactinib has been found to be clinically active in patients with KRAS mutant tumors. In an ongoing investigator-initiated Phase 1/2 FRAME study, the combination of VS-6766 and defactinib is being evaluated in patients with LGSOC, KRAS mutant NSCLC and colorectal cancer (CRC). Updated interim data from this study presented at the 2nd Annual RAS-Targeted Drug Development Summit in
About Verastem Oncology
Forward-Looking Statements Notice
This press release includes forward-looking statements about Verastem Oncology’s strategy, future plans and prospects, including statements related to the potential clinical value of the RAF/MEK/FAK combination and the anticipated timeline for Phase 2 registration-directed trials with VS-6766 in low grade serous ovarian cancer and KRAS mutant NSCLC. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," “can,” “promising” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement.
Applicable risks and uncertainties include the risks and uncertainties, among other things, regarding: the success in the development and potential commercialization of our product candidates, including defactinib in combination with VS-6766; the occurrence of adverse safety events and/or unexpected concerns that may arise from additional data or analysis or result in unmanageable safety profiles as compared to their levels of efficacy; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the scope, timing, and outcome of any legal proceedings; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of our product candidates; whether preclinical testing of our product candidates and preliminary or interim data from clinical trials will be predictive of the results or success of ongoing or later clinical trials; that the timing, scope and rate of reimbursement for our product candidates is uncertain; that third-party payors (including government agencies) may not reimburse; that there may be competitive developments affecting our product candidates; that data may not be available when expected; that enrollment of clinical trials may take longer than expected; that our product candidates will experience manufacturing or supply interruptions or failures; that we will be unable to successfully initiate or complete the clinical development and eventual commercialization of our product candidates; that the development and commercialization of our product candidates will take longer or cost more than planned; that we or Chugai Pharmaceutical Co., Ltd. will fail to fully perform under the VS-6766 (CH5126766) license agreement; that we may not have sufficient cash to fund our contemplated operations; that we may be unable to make additional draws under our debt facility or obtain adequate financing in the future through product licensing, co-promotional arrangements, public or private equity, debt financing or otherwise; that we will be unable to execute on our partnering strategies for defactinib in combination with VS-6766; that we will not pursue or submit regulatory filings for our product candidates, and that our product candidates will not receive regulatory approval, become commercially successful products, or result in new treatment options being offered to patients.
Other risks and uncertainties include those identified under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended
1 Gerber D. et al. Phase 2 study of the focal adhesion kinase inhibitor defactinib (VS-6063) in previously treated advanced KRAS mutant non-small cell lung cancer.
2 Chénard-Poirier, M. et al. Results from the biomarker-driven basket trial of RO5126766 (CH5127566), a potent RAF/MEK inhibitor, in RAS- or RAF-mutated malignancies including multiple myeloma.
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