Verastem Oncology Presents Two-Year Median Follow-Up Data for AVMAPKI®–FAKZYNJA® Combination in Recurrent Low-Grade Serous Ovarian Cancer at SGO 2026 Annual Meeting on Women’s Cancers
Verastem Oncology (Nasdaq: VSTM), a company dedicated to developing innovative therapies for cancers driven by the RAS/MAPK signaling pathway, has announced new long-term clinical data from its Phase 2 RAMP 201 trial evaluating the combination of avutometinib and defactinib. These updated results, reflecting approximately two years of median follow-up, are being presented during an oral plenary session at the Society of Gynecologic Oncology 2026 Annual Meeting on Women’s Cancers, taking place April 10–13, 2026, in San Juan.
The data focus on patients with recurrent low-grade serous ovarian cancer (LGSOC), a rare and challenging subtype of ovarian cancer characterized by slower growth but notable resistance to conventional chemotherapy. For this patient population, treatment options remain limited, making the development of targeted therapies an urgent clinical priority.
The combination therapy—marketed as AVMAPKI® (avutometinib capsules) and FAKZYNJA® (defactinib tablets)—targets key signaling pathways involved in tumor growth and survival. Avutometinib is designed to inhibit MEK signaling within the RAS/MAPK pathway, while defactinib targets focal adhesion kinase (FAK), a protein implicated in cancer cell adhesion, survival, and resistance mechanisms. Together, this dual-target approach aims to disrupt tumor progression more effectively than single-agent therapies.
According to the updated analysis, patients who remained on the combination therapy for two years continued to demonstrate durable clinical benefit, with efficacy outcomes consistent with earlier findings from the primary analysis. These results provide encouraging evidence that long-term treatment with the combination can maintain response levels while remaining tolerable for patients.
Dr. Rachel Grisham, the presenting investigator for the RAMP 201 study and Section Head of Ovarian Cancer at Memorial Sloan Kettering Cancer Center, emphasized the significance of these findings. She noted that patients who continued therapy over extended periods were able to sustain both response and duration of treatment, suggesting that the regimen can provide ongoing benefit with manageable toxicity. As the field approaches the one-year anniversary of regulatory approval for the combination, these long-term data further validate its role as a meaningful treatment option for patients with recurrent disease.
The updated dataset includes patients with a median follow-up of approximately 24.9 months. Key efficacy endpoints—such as median duration of response (mDOR) and median progression-free survival (mPFS)—remained consistent with those reported in the earlier primary analysis, which had a shorter follow-up period. Notably, the median duration of response reached 31.1 months in the overall population, highlighting the durability of clinical benefit. Similarly, median progression-free survival remained stable at around 12.9 months across analyses.
Subgroup analyses provided additional insights into treatment outcomes based on KRAS mutation status. Among patients with KRAS-mutated tumors, median progression-free survival reached up to 19.6 months in the long-term follow-up group, compared to 12.7 months in those with KRAS wild-type disease. Importantly, both groups demonstrated meaningful benefit, underscoring the broad applicability of the therapy across different molecular subtypes of LGSOC.
Treatment persistence was another notable finding. Approximately 50 percent of patients with KRAS-mutated disease and 30 percent of those with KRAS wild-type tumors remained on therapy for more than one year. This level of sustained treatment exposure is particularly significant in a setting where patients often experience limited durable responses with existing therapies.
Safety outcomes from the extended follow-up were consistent with earlier observations, with no new safety signals identified. Adverse events remained manageable, and the overall discontinuation rate due to treatment-related side effects was relatively low at 12 percent. These findings suggest that the combination therapy can be administered over long periods without compromising patient safety.
Dr. Bradley Monk, an investigator in the RAMP 201 trial and a specialist at Florida Cancer Specialists & Research Institute, highlighted the clinical relevance of the data. He noted that the ability to maintain patients on therapy for extended durations—particularly those without KRAS mutations—represents a meaningful advancement in a disease setting with few effective options. He also emphasized that the manageable safety profile and the use of dose adjustments to maintain treatment intensity distinguish this regimen from earlier MEK inhibitor-based approaches.
In addition to the RAMP 201 findings, Verastem Oncology presented results from an exposure-response analysis examining the relationship between drug dosing, efficacy, and safety. This analysis included data from multiple studies, including RAMP 201, RAMP 202, and the FRAME trial, encompassing a broader patient population.
The analysis demonstrated that the currently approved dosing regimen—avutometinib 3.2 mg administered twice weekly in combination with defactinib 200 mg taken twice daily—provides the optimal balance between efficacy and tolerability. While lower doses of avutometinib may reduce the incidence of treatment-emergent adverse events (TEAEs), they may also compromise therapeutic effectiveness.
Among the most commonly reported adverse events were skin-related disorders, gastrointestinal toxicities, elevations in liver function tests, and increases in creatine phosphokinase levels. However, the study findings indicate that these side effects can be effectively managed through dose interruptions and supportive care measures, allowing patients to resume treatment at the recommended dose without significant loss of benefit.
Importantly, the ability to manage adverse events without permanently discontinuing therapy is a key advantage of this treatment approach. By maintaining dose intensity over time, clinicians can help maximize the therapeutic impact while minimizing disruptions to patient care.
The presentation of these data at the Society of Gynecologic Oncology 2026 Annual Meeting on Women’s Cancers highlights the growing interest in targeted therapies for ovarian cancer and the importance of ongoing clinical research in this field. As new insights emerge, they contribute to a more nuanced understanding of how to optimize treatment strategies for patients with complex and heterogeneous diseases like LGSOC.
In conjunction with its scientific presentations, Verastem Oncology is also engaging with the oncology community through its presence at the conference exhibition hall. The company’s booth provides an opportunity for clinicians and researchers to learn more about its approved therapies, ongoing clinical trials, and broader research initiatives.
Overall, the two-year follow-up data from the RAMP 201 trial reinforce the potential of the avutometinib and defactinib combination as a durable and well-tolerated treatment option for patients with recurrent low-grade serous ovarian cancer. These findings not only support its current clinical use but also provide a strong foundation for future research aimed at further improving outcomes for patients facing this challenging disease.
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. Oncology 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 Oncology 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 Oncology 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. Verastem Oncology is also evaluating avutometinib plus defactinib with standard-of-care chemotherapy as a potential treatment in the first-line for patients with advanced pancreatic cancer (RAMP 205; NCT05669482).
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.
Source Link:https://www.businesswire.com/
