Verastem Oncology Announces New RAMP 201 Molecular Profiling and External Control Arm Analyses Describing Outcomes for Avutometinib Plus Defactinib in Recurrent Low-Grade Serous Ovarian Cancer to be Presented at IGCS 2026

The external control analysis found higher weighted response rates than conventional care in both KRAS-mutated and KRAS wild-type disease.

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RAMP 201 molecular profiling showed clinically meaningful activity in KRAS wild-type recurrent LGSOC, including ORRs of 22% in patients with NRAS- or BRAF-mutated tumors and 18% in patients with KRAS/NRAS/BRAF triple wild-type tumors

External control analysis showed higher weighted ORR and statistically significant improvements in PFS versus conventional care in both KRAS-mutated and KRAS wild-type subgroups

BOSTON--(BUSINESS WIRE)-- Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, today announced data from a new molecular profiling and tumor biomarker analysis of the Phase 2 RAMP 201 clinical trial of avutometinib plus defactinib in patients with recurrent low-grade serous ovarian cancer (LGSOC), as well as a new external control arm analysis comparing outcomes from RAMP 201 with conventional care. The analyses will be presented today at the International Gynecologic Cancer Society (IGCS) 2026 Annual Global Meeting in Montréal, Canada, October 1-3, 2026. Encore data from the Phase 2 RAMP 201J study in Japanese patients are also being featured in a rapid oral presentation.

Rapid Orals: Molecular Profiling and Tumor Biomarker Analysis of RAMP 201, A Study Demonstrating Efficacy of Avutometinib in Combination with Defactinib in Recurrent Low-Grade Serous Ovarian Cancer

Date and Time: October 2, 2026, 10:30 - 11:30​ a.m. ET

Molecular profiling of baseline tumor samples from RAMP 201 was conducted to assess the activity of avutometinib plus defactinib across molecularly defined subgroups within the KRAS wild-type recurrent LGSOC population.

Among patients with KRAS wild-type LGSOC, 81% also had no NRAS and BRAF mutations. In this triple wild-type (KRAS/NRAS/BRAF) population, avutometinib plus defactinib demonstrated clinically meaningful activity, with a confirmed objective response rate (ORR) of 18% (7/39) and median progression-free survival (mPFS) of 13 months. Among patients with KRAS wild-type LGSOC with NRAS or BRAF mutations, the combination achieved a confirmed ORR of 22% (2/9).

“Patients whose tumors are wild-type for KRAS, NRAS, and/or BRAF have typically experienced response rates under 10% with trametinib, chemotherapy or endocrine therapy,” said Professor Susana Banerjee, M.B.B.S., M.A., Ph.D., F.R.C.P, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust and Team Leader in Women's Cancers at The Institute of Cancer Research, London and Global Lead Principal Investigator of ENGOTov60/GOG3052/NCRI/RAMP201. “This analysis provides additional insight into molecular biology of recurrent LGSOC and suggests that targeting RAF, MEK, and FAK with avutometinib plus defactinib may provide clinically meaningful benefit beyond tumors driven by KRAS, NRAS or BRAF mutations.”

Poster Rounds with the Professor: Efficacy of Avutometinib and Defactinib vs Conventional Care in Low-Grade Serous Ovarian Cancer (LGSOC): An External Control Arm Analysis

Date and Time: October 2, 2026, 2:25 – 2:30 p.m. ET

The external control arm analysis compared outcomes among patients treated with avutometinib plus defactinib in RAMP 201 with a matched and reweighted cohort treated with conventional care, chemotherapy or anti-estrogen therapy, from the GOG 281 trial.

Among patients with KRAS-mutated LGSOC, weighted ORR was 38.7% with avutometinib plus defactinib versus 0% with conventional care and median weighted PFS was 22.1 months versus 6.5 months, respectively. Among patients with KRAS wild-type LGSOC, weighted ORR was 22.7% with avutometinib plus defactinib versus 7.9% with conventional care and median weighted PFS was 11.3 months versus 7.7 months, respectively.

“Taken together, the molecular profiling and external control arm analyses adds to the body of evidence of the potential of avutometinib plus defactinib to treat recurrent LGSOC in both KRAS-mutated and KRAS wild-type disease,” said Michael Kauffman, M.D., Ph.D., president of development at Verastem Oncology. “The molecular profiling data show activity across biologically distinct subgroups of KRAS wild-type disease, including triple wild-type tumors, while the external control analysis shows higher response rates and statistically significant improvements in PFS over conventional care. Building on the established activity in KRAS-mutated recurrent LGSOC, these findings reinforce the approved use of avutometinib plus defactinib at first recurrence for patients with KRAS-mutated LGSOC, and the potential of combined RAF/MEK and FAK targeting to provide clinically meaningful benefit to a broader population of patients with KRAS wild-type recurrent LGSOC, many of whom have historically experienced poorer outcomes.”

Rapid Oral Presentation: Avutometinib and Defactinib in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC): A Phase II Study in Japanese Patients (RAMP 201J)

Date and Time: October 2, 2026, 10:30 - 11:30​ a.m. ET

This encore presentation includes results from RAMP 201J previously reported at the Annual Meeting of the Japanese Society of Gynecologic Oncology, held July 17–19, 2026, in Sapporo, Japan. As of May 29, 2026, 16 efficacy-evaluable patients with recurrent LGSOC received avutometinib plus defactinib, with a median follow-up of 12.4 months.

The combination achieved a 44% ORR and 94% disease control rate across all patients. ORRs were 71% in patients with KRAS-mutated tumors and 22% in those with KRAS wild-type tumors, with disease control rates of 100% and 89%, respectively. Overall, 94% of patients experienced tumor shrinkage, and 11 of 16 remained on treatment at the data cutoff.

​At the IGCS 2026 Annual Global Meeting, visit Verastem’s exhibition booth (#01) for more information on its approved therapy and ongoing cancer research. The full schedule and full presentation abstracts are available on the IGCS Annual Global Meeting web site.

About RAMP 201
RAMP 201 (ENGOTov60/GOG3052/NCRI) (NCT04625270) was an adaptive, two-part multicenter, parallel cohort, randomized, open-label Phase 2 registration-directed trial evaluating the efficacy and safety of avutometinib alone and in combination with defactinib in patients with recurrent low-grade serous ovarian cancer (LGSOC). The first part of the trial (Part A) determined the selection of the go-forward regimen, which was the combination of avutometinib and defactinib versus avutometinib alone, based on overall response rates. The expansion phases of the trial (Parts B and C) evaluated the safety and efficacy of the go-forward regimen of avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily. The Part D portion of the trial evaluated a low dose of the combination to inform individualized dose reduction.

About Low-Grade Serous Ovarian Cancer (LGSOC)
LGSOC is a rare ovarian cancer that is insidious and persistent. LGSOC is distinct and different from high-grade serous ovarian cancer (HGSOC) and requires different treatment. LGSOC is highly recurrent and less sensitive to chemotherapy compared to HGSOC. Approximately 6,000-8,000 women in the U.S. and 80,000 worldwide are living with this disease. LGSOC affects younger women with bimodal peaks of diagnosis at ages between 20-30 and 50-60 and has a median survival of approximately ten years. Approximately 70 percent of LGSOC shows RAS pathway-associated mutations, and 30 percent of people with LGSOC have a KRAS mutation. The majority of patients report a negative impact of LGSOC on their mental and physical health, fertility, and long-term quality of life.

About AVMAPKI and FAKZYNJA Combination Therapy
AVMAPKI (avutometinib) inhibits MEK kinase activity while also blocking the compensatory reactivation of MEK by upstream RAF. RAF and MEK proteins are regulators of the RAS/RAF/MEK/ERK (MAPK) pathway. Blocking RAF and/or MEK activates FAK, a key mediator of drug resistance. FAKZYNJA (defactinib) is a FAK inhibitor and together, the avutometinib and defactinib combination was designed to provide a more complete blockade of the signaling that drives the growth and drug resistance of RAS/MAPK pathway-dependent tumors.

The U.S. Food and Drug Administration (FDA) approved AVMAPKI^® FAKZYNJA^® CO-PACK (avutometinib capsules; defactinib tablets) for the treatment of adult patients with KRAS-mutated recurrent LGSOC who have received prior systemic therapy on May 8, 2025. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Verastem is conducting RAMP 301 (GOG-3097/ENGOT-ov81/GTG-UK) (NCT06072781), an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC) with and without a KRAS mutation. In June 2026, Verastem provided updated results on the Phase 1/2 RAMP 205 trial (NCT05669482), which is evaluating avutometinib plus defactinib in combination with standard-of-care chemotherapy as a first-line treatment for patients with advanced pancreatic cancer. Avutometinib and defactinib are not approved by the FDA or any other regulatory authority, either in combination or with other therapies, for any of these investigative uses. Neither avutometinib nor defactinib are approved by the FDA or any other regulatory authority on a stand-alone basis for any use.

AVMAPKI FAKZYNJA CO-PACK U.S. Indication

Indication

AVMAPKI FAKZYNJA CO-PACK is indicated for the treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Important Safety Information

Warnings and Precautions

• Ocular Toxicities: Ocular toxicities, including visual impairment and vitreoretinal disorders, occurred. Perform comprehensive ophthalmic evaluation at baseline, prior to cycle 2, every three cycles thereafter, and as clinically indicated. Withhold AVMAPKI FAKZYNJA CO-PACK for ocular toxicities until improvement at the same or reduced dose. Permanently discontinue AVMAPKI FAKZYNJA CO-PACK for any grade 4 toxicity.
• Serious Skin Toxicities: Skin toxicities, including photosensitivity and severe cutaneous adverse reactions (SCARSs) occurred. Adhere to concomitant medications. Monitor for skin toxicities and interrupt, reduce or permanently discontinue AVMAPKI FAKZYNJA CO-PACK based on severity, tolerability and duration.
• Hepatotoxicity: Monitor liver function tests prior to each cycle, on day 15 of the first 4 cycles, and as clinically indicated. Withhold, reduce or discontinue AVMAPKI FAKZYNJA CO-PACK based on severity and persistence of abnormality.
• Rhabdomyolysis: Monitor creatine phosphokinase prior to the start of each cycle, on day 15 of the first four cycles, and as clinically indicated. If increased CPK occurs, evaluate patients for rhabdomyolysis or other causes. Withhold, reduce or permanently discontinue AVMAPKI FAKZYNJA CO-PACK based on severity and duration of the adverse reaction.
• Embryo-Fetal Toxicity: AVMAPKI FAKZYNJA CO-PACK can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Adverse Reactions

The most common (≥ 25%) adverse reactions, including laboratory abnormalities, were increased creatine phosphokinase, nausea, fatigue, increased aspartate aminotransferase, rash, diarrhea, musculoskeletal pain, edema, decreased hemoglobin, increased alanine aminotransferase, vomiting, increased blood bilirubin, increased triglycerides, decreased lymphocyte count, abdominal pain, dyspepsia, dermatitis acneiform, vitreoretinal disorders, increased alkaline phosphatase, stomatitis, pruritus, visual impairment, decreased platelet count, constipation, dry skin, dyspnea, cough, urinary tract infection, and decreased neutrophil count.

Drug Interactions

• Strong and moderate CYP3A4 inhibitors: Avoid concomitant use with AVMAPKI FAKZYNJA CO-PACK.
• Strong and moderate CYP3A4 inducers: Avoid concomitant use with AVMAPKI FAKZYNJA CO-PACK.
• Warfarin: Avoid concomitant use of AVMAPKI FAKZYNJA CO-PACK with warfarin and use an alternative to warfarin.
• Gastric acid reducing agents: Avoid concomitant use of AVMAPKI FAKZYNJA CO-PACK with proton pump inhibitors (PPIs) or H2 receptor antagonists. If use of an acid-reducing agent cannot be avoided, administer FAKZYNJA 2 hours before or 2 hours after the administration of a locally acting antacid.

Use in Specific Populations

• Lactation: Advise not to breastfeed.
• Fertility: May impair fertility in males and females.

Click here for full Prescribing Information.

About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a biopharmaceutical company committed to developing and commercializing new medicines to improve the lives of patients diagnosed with RAS/MAPK pathway-driven cancers. Verastem markets AVMAPKI^® FAKZYNJA^® CO-PACK in the U.S. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition, FAK inhibition, and KRAS G12D inhibition. For more information, please visit www.verastem.com and follow us on LinkedIn.

Forward-Looking Statements
This press release includes forward-looking statements. These forward-looking statements generally can be identified by the use of words such as “anticipate,” “expect,” “plan,” “could,” “may,” “believe,” “estimate,” “forecast,” “goal,” “project,” and other words of similar meaning. Such forward-looking statements address various matters about, among other things, Verastem Oncology’s programs and product candidates, strategy, future plans and prospects, including statements related to the potential for and timing of commercialization of product candidates, the expected outcome and benefits of the Company’s collaboration with GenFleet Therapeutics (Shanghai), Inc., the timing of commencing and completing trials and compiling data, the Company’s proforma cash position, the expected timing of the presentation of data by the Company and the potential clinical value of various of the Company’s clinical trials. Each forward-looking statement contained in this press release is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include, among others: the uncertainties inherent in research and development, such as the possibility of negative or unexpected results of clinical trials; that we may 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, or that GenFleet may fail to fully perform under the agreement; that we may not be successful in our continued commercialization of AVMAPKI FAKZYNJA CO-PACK; that we may not satisfy the closing conditions to receive $50.0 million from our non-dilutive royalty financing arrangement with Oberland Capital; that the development and commercialization of our product candidates may take longer or cost more than planned, including as a result of conducting additional studies or our decisions regarding execution of such commercialization; that data may not be available when expected; risks associated with preliminary and interim data, which may not be representative of more mature data; risks associated with the regulatory and policy actions proposed and enacted by the current U.S. presidential administration that may adversely affect our business; risks associated with the current administration’s reductions to the FDA’s workforce and any subsequent reductions that may lead to disruptions and delays in the FDA’s review and oversight of our product candidates and impact the FDA’s ability to provide timely feedback on our development programs; that our product candidates may not receive regulatory approval, become commercially successful products, or result in new treatment options being offered to patients; and the risks identified under the heading "Risk Factors" as detailed in the Company’s Annual Report on Form 10-K for the year ended December 31, 2025, as filed with the Securities and Exchange Commission (SEC) on March 4, 2026, as well as the other information we file with the SEC, are possibly realized. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. You are encouraged to read our filings with the SEC, available at www.sec.gov, for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this press release, and we undertake no obligation to update or revise any of these statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.

View source version on businesswire.com: https://www.businesswire.com/news/home/20261002351312/en/

For Investor and Media Inquiries:
Julissa Viana
Senior Vice President, Corporate Communications,
Investor Relations & Patient Advocacy
investors@verastem.com  or
media@verastem.com

Source: Verastem Oncology

Key Terms

objective response rate medical

The objective response rate (ORR) is the percentage of patients in a clinical trial whose tumors measurably shrink or disappear according to preset rules. Investors use it as a quick, objective signal of a drug’s ability to produce a clear treatment effect—like counting how many plants visibly respond after applying a new fertilizer—and higher ORR can improve odds of regulatory approval, commercial success, and company valuation.

progression-free survival medical

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

external control arm medical

A external control arm is a comparison group for a clinical study made from data collected outside the trial—such as past trials, medical records, or registries—instead of using patients randomized within the same study. It matters to investors because using outside data can speed development and lower costs but also introduces uncertainty about how comparable the groups are, which can affect regulatory decisions, perceived drug effectiveness, and the commercial value of a therapy.

accelerated approval regulatory

Accelerated approval is a process that allows new medical treatments to be approved more quickly than usual if they address serious or life-threatening conditions and show promising early results. For investors, it signals that a treatment may reach the market sooner, potentially boosting a company's prospects, but it also involves some uncertainty since full evidence of effectiveness is still being gathered.