83% (5/6) of patients achieved a confirmed
partial response in cohort 1, the most mature dose level; one
dose-limiting toxicity was observed, however, the dose level was
subsequently cleared after additional patients were enrolled
Follow up of patients in the additional dose
and schedule cohorts is ongoing to determine the recommended Phase
2 dose for study expansion
Poster presentation on Saturday, June 1, 2024
at the ASCO Annual Meeting
Company to host investor conference call and
webcast on Friday, May 24, 2024 at 8:00 am EDT to discuss these
data
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company
committed to advancing new medicines for patients with cancer,
today announced the initial interim safety and efficacy results
from the ongoing RAMP 205 Phase 1/2 clinical trial evaluating
avutometinib plus defactinib in combination with gemcitabine and
Nab-paclitaxel in the first-line in patients with metastatic
pancreatic cancer. As of May 14, 2024, patients receiving the
combination of avutometinib and defactinib with gemcitabine and
Nab-paclitaxel in dose level 1 cohort achieved a confirmed overall
response rate (ORR) of 83% (5/6), one dose-limiting toxicity (DLT)
was observed in the dose level 1 cohort, and the dose level was
subsequently cleared after additional patients were enrolled. The
initial interim results will be presented at the upcoming American
Society of Clinical Oncology (ASCO) Annual Meeting on June 1, 2024,
in a poster session from 1:30-4:30 pm CDT in Chicago, IL.
“The initial interim results from the RAMP 205 trial evaluating
avutometinib and defactinib in combination with standard of care
first-line chemotherapy are encouraging and demonstrate the
importance of targeting the RAS/MAPK pathway, as more than 90% of
pancreatic tumors have a KRAS mutation. We continue to progress the
study evaluating other dose and schedule regimens to determine the
recommended Phase 2 dose in the trial,” said John Hayslip, M.D.,
chief medical officer of Verastem Oncology. "Metastatic pancreatic
cancer continues to be a challenging cancer to treat and these data
support the intent behind the Therapeutic Accelerator Award that we
received from PanCAN to develop new therapies faster and more
efficiently than in historical studies.”
“Verastem was the inaugural recipient of the PanCAN Therapeutic
Accelerator Award, which has been an important part of PanCAN’s
approach to advancing innovative treatments for pancreatic cancer,”
said Anna Berkenblit, M.D., MMSc, Chief Scientific and Medical
Officer at PanCAN. “We look forward to Verastem presenting their
initial data from the Phase 1b/2a trial of avutometinib and
defactinib in combination with standard care gemcitabine and
Nab-paclitaxel in previously untreated metastatic pancreatic cancer
at ASCO. There is a critical need for new treatment options in this
disease, and we hope that the results from this study lead to
improved outcomes for patients with pancreatic cancer.”
Initial Interim Data from RAMP 205 from the Ongoing Phase 1/2
Clinical Trial
As of a data cutoff of May 14, 2024, 41 patients had been
treated in one of four dose and schedule cohort regimens of
avutometinib and defactinib with gemcitabine and
Nab-paclitaxel:
- In dose level 1, 6 patients received 2.4 mg of avutometinib
twice a week (BIW), 200 mg of defactinib twice a day (BID) for 3
weeks out of every 4 and 800 mg/m2 of gemcitabine and 125 mg/m2 of
Nab-paclitaxel on a schedule of day 1, day 8 and day 15.
- In dose level -1, 11 patients received 2.4 mg of avutometinib
twice a week (BIW), 200 mg of defactinib twice a day (BID) for 3
weeks out of every 4 with 800 mg/m2 of gemcitabine and 100 mg/m2 of
Nab-paclitaxel on a schedule of day 1, day 8 and day 15.
- In dose level 1a, 12 patients received 3.2 mg of avutometinib
twice a week (BIW), 200 mg of defactinib twice a day (BID) for 3
weeks out of every 4 with 800 mg/m2 of gemcitabine and 125 mg/m2 of
Nab-paclitaxel on a schedule of day 1 and day 15.
- In dose level 2a, 12 patients received 3.2 mg of avutometinib
twice a week (BIW), 200 mg of defactinib twice a day (BID) for 3
weeks out of every 4 with 1000 mg/m2 of gemcitabine and 125 mg/m2
of Nab-paclitaxel on a schedule of day 1 and day 15.
As of May 14, 2024, in the dose level 1 cohort, 83% (5/6) of
patients achieved a confirmed partial response with more than six
months of follow-up at the time of data cutoff. Of the 26 patients
in all cohorts who have had the opportunity to have their first
scan while on treatment, 21 have experienced a reduction of the
change in target lesion sum of diameters.
Patients in the trial had a median age of 64 years, 46% were
male and 49% had an Eastern Cooperative Oncology Group (ECOG)
Performance Status of one.
Initial Interim Safety Data from All Dose Cohorts
As of the May 14, 2024 data cutoff, 12 patients experienced 19
treatment emergent serious adverse events (SAEs), 11 patients with
grade ≥3. Grade ≥3 treatment emergent SAEs included blood bilirubin
increased (n=2), biliary obstruction (n=2), febrile neutropenia
(n=2), pulmonary embolism (n=2), sepsis (n=2), anaemia (n=1),
pneumoperitoneum (n=1), septic shock (n=1), skin infection (n=1),
malignant neoplasm progression (n=1) and vomiting (n=1). Two
patients discontinued treatment due to treatment emergent adverse
events (febrile neutropenia, blood bilirubin increased, and
detachment of retinal pigment epithelium).
One dose-limiting toxicity of febrile neutropenia was observed
in the dose level 1 cohort and the dose cohort was cleared after
additional patients were evaluated. In the additional dose cohorts
enrolled more recently (-1, 1a, and 2a), follow up is ongoing and
most patients remained on treatment at data cutoff.
Conference Call and Webcast Information
Verastem will hold an investor conference call and webcast on
Friday, May 24 at 8:00 am EDT, to discuss these data. The call will
feature members of Verastem’s management team. To access the
conference call, please dial (844) 763-8274 (local) or (412)
717-9224 (international) at least 10 minutes prior to the start
time and ask to be joined into the Verastem Oncology conference
call. A live audio webcast of the call, along with accompany
slides, will be accessible here.
About Metastatic Pancreatic Cancer
Pancreatic cancer is the third leading cancer in the U.S. and
seventh leading cause of cancer-associated mortality worldwide.
Metastatic pancreatic cancer is defined as stage IV cancer, where
the cancer spreads to other organs. In the U.S., over 30,000
patients are diagnosed with metastatic pancreatic cancer each
year1,2, for which the five-year survival rate is 3%2. Globally,
over 240,000 patients are diagnosed with metastatic pancreatic
cancer each year3. More than 90% of pancreatic cancers have a KRAS
mutation4. The standard of care consists of surgery, chemotherapy,
radiation or a combination of these approaches5.
About RAMP 205 Phase 1/2 Study
RAMP 205 is a multicenter, open-label, single arm Phase 1b/2a
study designed to evaluate the safety, tolerability and efficacy of
avutometinib and defactinib in combination with standard of care
chemotherapy (gemcitabine and Nab-paclitaxel) in patients with
previously untreated metastatic pancreatic ductal adenocarcinoma.
Part A of the study will evaluate different dose and schedule
combinations to determine the recommended Phase 2 dose for
expansion into Part B. RAMP 205 is supported by a PanCAN
Therapeutic Accelerator Award.
About the Avutometinib and Defactinib Combination
Avutometinib is an investigational RAF/MEK clamp that is
designed to induce inactive complexes of MEK with ARAF, BRAF and
CRAF potentially creating a more complete and durable anti-tumor
response through maximal RAS/MAPK pathway inhibition. Avutometinib
is designed to block both MEK kinase activity and the ability of
RAF to phosphorylate MEK. This differentiated proposed mechanism
potentially allows avutometinib to block MEK signaling without the
compensatory activation of MEK that appears to limit the efficacy
of other MEK-only inhibitors. The U.S. Food and Drug Administration
(FDA) granted Breakthrough Therapy Designation of the
investigational combination of avutometinib and defactinib, a
selective FAK inhibitor, for the treatment of all patients with
recurrent low-grade serous ovarian cancer (LGSOC) regardless of
KRAS status after one or more prior lines of therapy, including
platinum-based chemotherapy. Avutometinib alone or in combination
with defactinib was also granted Orphan Drug Designation by the FDA
for the treatment of LGSOC.
Verastem Oncology is currently conducting clinical trials with
avutometinib in RAS/MAPK driven tumors as part of its Raf
And Mek Program or RAMP. RAMP 301
(NCT06072781) is an international Phase 3 confirmatory trial
evaluating the combination of avutometinib and defactinib versus
standard chemotherapy or hormonal therapy for the treatment of
recurrent LGSOC. RAMP 201 (NCT04625270) is a Phase 2
registration-directed trial of avutometinib in combination with
defactinib in patients with recurrent LGSOC and enrollment has been
completed in each of the dose optimization and expansion phases and
the low-dose evaluation.
Verastem Oncology has established clinical collaborations with
Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) in combination
with avutometinib and defactinib and KRAZATI™ (adagrasib) in
combination with avutometinib in KRAS G12C mutant NSCLC as part of
the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials,
respectively. The RAMP 205 (NCT05669482), a Phase 1b/2 clinical
trial evaluating avutometinib and defactinib with
gemcitabine/Nab-paclitaxel in patients with front-line metastatic
pancreatic cancer, is supported by the PanCAN Therapeutic
Accelerator Award.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a late-stage development
biopharmaceutical company committed to the development and
commercialization of new medicines to improve the lives of patients
diagnosed with cancer. Our pipeline is focused on RAS/MAPK-driven
cancers, specifically novel small molecule drugs that inhibit
critical signaling pathways in cancer that promote cancer cell
survival and tumor growth, including RAF/MEK inhibition and FAK
inhibition. For more information, please visit www.verastem.com and
follow us on LinkedIn.
Forward Looking Statements
This press release includes forward-looking statements about,
among other things, Verastem Oncology’s programs and product
candidates, strategy, future plans and prospects, including
statements related to the potential clinical value of various of
the Company’s clinical trials, including the RAMP 201, RAMP 205 and
RAMP 301 trials, the timing of commencing and completing trials,
including the RAMP 205 trial topline data reports, interactions
with regulators, the potential for and timing of commercialization
of product candidates and potential for additional development
programs involving Verastem Oncology’s lead compound. 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. Forward-looking statements are not
guarantees of future performance and are 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 avutometinib in combination with other
compounds, including defactinib, LUMAKRAS™ and others; the
uncertainties inherent in research and development, such as
negative or unexpected results of clinical trials, the occurrence
or timing of applications for our product candidates that may be
filed with regulatory authorities in any jurisdictions; whether and
when regulatory authorities in any jurisdictions may approve any
such applications that may be filed for our product candidates,
and, if approved, whether our product candidates will be
commercially successful in such jurisdictions; 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 trial design, labeling and other matters that
could affect the timing, 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; the market opportunities
of our drug candidates are based on internal and third-party
estimates which may prove to be incorrect; 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 or that the FDA may
require the Company to enroll additional patients in the Company’s
ongoing RAMP-301 confirmatory Phase 3 clinical trial prior to
submitting an NDA seeking accelerated approval; that our product
candidates will cause adverse safety events and/or unexpected
concerns may arise from additional data or analysis, or result in
unmanageable safety profiles as compared to their levels of
efficacy; that we may be unable to successfully validate, develop
and obtain regulatory approval for companion diagnostic tests for
our product candidates that require or would commercially benefit
from such tests, or experience significant delays in doing so; that
our product candidates may experience manufacturing or supply
interruptions or failures; that any of our third party contract
research organizations, contract manufacturing organizations,
clinical sites, or contractors, among others, who we rely on fail
to fully perform; that we face substantial competition, which may
result in others developing or commercializing products before or
more successfully than we do which could result in reduced market
share or market potential for our product candidates; 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,
including as a result of conducting additional studies; that we may
not have sufficient cash to fund our contemplated operations; that
we may not attract and retain high quality personnel; that we or
Chugai Pharmaceutical Co., Ltd. will fail to fully perform under
the avutometinib license agreement; that our target market for our
product candidates might be smaller than we are presently
estimating; that Secura Bio, Inc. will fail to fully perform under
the asset purchase agreement with Secura Bio, Inc., including in
relation to milestone payments; that we will not see a return on
investment on the payments we have and may continue to make
pursuant to the collaboration and option agreement with GenFleet
Therapeutics (Shanghai), Inc. (GenFleet), or that GenFleet will
fail to fully perform under the agreement; that we may be unable to
obtain adequate financing in the future through product licensing,
co-promotional arrangements, public or private equity, debt
financing or otherwise; 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 December 31, 2023 as filed with the Securities
and Exchange Commission (SEC) on March 14, 2024 and in any
subsequent filings with the SEC. The forward-looking statements
contained in this press release reflect Verastem Oncology’s views
as of the date hereof, and the Company does not assume and
specifically disclaims any obligation to update any forward-looking
statements whether as a result of new information, future events or
otherwise, except as required by law.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240523300933/en/
For Investor and Media Inquiries: Julissa Viana Vice
President, Corporate Communications and Investor Relations
investors@verastem.com or media@verastem.com
Verastem (NASDAQ:VSTM)
Historical Stock Chart
Von Dez 2024 bis Jan 2025
Verastem (NASDAQ:VSTM)
Historical Stock Chart
Von Jan 2024 bis Jan 2025
