Verastem Oncology Presents Two-Year Follow-Up Data Highlighting Durable Benefits of AVMAPKI and FAKZYNJA Combination in Recurrent LGSOC
Verastem Oncology has announced updated findings from the Phase 2 RAMP 201 clinical trial, showcasing two-year median follow-up data for its combination therapy of avutometinib and defactinib The data, presented at the Society of Gynecologic Oncology (SGO) 2026 Annual Meeting on Women’s Cancers in San Juan, Puerto Rico, reinforce the long-term efficacy, durability, and manageable safety profile of the treatment in patients with recurrent low-grade serous ovarian cancer (LGSOC).
Sustained Clinical Benefits Over Two Years
The updated analysis demonstrates that patients treated with the combination therapy continue to experience meaningful and sustained clinical benefits across multiple efficacy measures. With a median follow-up period of approximately 24.9 months, results indicate that the durability of response remains consistent with earlier findings from the primary analysis conducted over a year prior.
Key efficacy endpoints, including median duration of response (mDoR) and median progression-free survival (mPFS), showed stable and encouraging outcomes. Patients with KRAS mutations exhibited particularly strong responses, with a median duration of response reaching 31.1 months and progression-free survival extending up to 19.6 months. Meanwhile, patients with KRAS wild-type disease also demonstrated clinically relevant benefits, albeit at slightly lower levels.
These findings suggest that the combination therapy not only provides initial tumor control but also maintains its effectiveness over extended treatment periods.
Long-Term Treatment Retention Rates
An important highlight from the study is the proportion of patients who remained on therapy beyond one year. Data revealed that approximately 52% of patients with KRAS-mutated LGSOC and 30% of those with KRAS wild-type disease continued treatment for more than 12 months.
This level of treatment persistence underscores both the tolerability and effectiveness of the regimen. In a disease setting where treatment options are limited and long-term disease control is challenging, the ability to sustain therapy for extended durations is a critical indicator of clinical benefit.
Consistent Safety Profile with No New Signals
Safety outcomes from the two-year follow-up remained consistent with the initial analysis, with no new safety concerns identified. The combination therapy continued to demonstrate a well-tolerated profile, supporting its suitability for long-term use.
Adverse events (AEs) observed during the extended follow-up were in line with previously reported data. Importantly, only 12% of patients discontinued treatment due to adverse events, reflecting a relatively low discontinuation rate.
Common treatment-emergent adverse events included:
- Skin-related disorders
- Gastrointestinal toxicities
- Elevated liver function tests
- Increased creatine phosphokinase levels
Despite these events, most were manageable through dose adjustments, interruptions, or supportive care, allowing patients to continue therapy without significant compromise to treatment outcomes.
Expert Insights on Long-Term Efficacy
Clinical investigators emphasized the significance of these findings in the context of recurrent LGSOC treatment. According to leading researchers involved in the study, patients who remained on the combination therapy for two years were able to maintain the same level of response observed in earlier analyses.
This consistency highlights the potential for long-term disease control with manageable toxicity, making the regimen a promising option for patients requiring extended therapy. Experts also noted that the ability to maintain dose intensity through temporary dose interruptions is a key advantage, distinguishing this approach from earlier MEK inhibitor-based treatments.
Clinically Meaningful Outcomes in KRAS Wild-Type Patients
While KRAS-mutated patients showed stronger responses overall, the data also revealed encouraging outcomes for patients with KRAS wild-type LGSOC. Approximately one-third of these patients remained on therapy for over a year, a notable achievement given the historically limited treatment options available for this subgroup.
This finding suggests that the combination therapy may have broader applicability across different molecular subtypes of LGSOC, expanding its potential impact in clinical practice.
Exposure-Response Analysis Supports Approved Dosing
In addition to the clinical trial results, a poster presentation at the SGO meeting highlighted findings from an exposure-response analysis involving patients from the FRAME, RAMP 201, and RAMP 202 studies.
The analysis demonstrated that the optimal therapeutic effect is achieved when using the FDA-approved dosing regimen:
- Avutometinib: 3.2 mg twice weekly
- Defactinib: 200 mg twice daily
All key efficacy endpoints—including overall response rate, duration of response, and tumor shrinkage—were maximized at this dosing schedule.
Although lower doses of avutometinib were associated with reduced adverse events, they also showed diminished efficacy. This reinforces the importance of maintaining the approved dose to achieve the best clinical outcomes.
Managing Adverse Events Without Compromising Efficacy
A critical insight from the exposure-response analysis is that adverse events can be effectively managed without permanently reducing the dose. Temporary dose interruptions were shown to help control side effects, after which patients could resume treatment at the full approved dose.
This strategy allows clinicians to balance safety and efficacy, ensuring that patients can continue benefiting from therapy while minimizing treatment-related complications.
Such flexibility in dosing management is particularly valuable in long-term treatment settings, where maintaining therapeutic intensity is essential for sustained disease control.
Reinforcing Confidence in Real-World Use
The two-year follow-up data provide strong support for the real-world application of the avutometinib and defactinib combination. The consistency between the updated analysis and earlier results adds confidence in the therapy’s reliability and durability.
For patients living with recurrent LGSOC—a rare and often treatment-resistant form of ovarian cancer—these findings represent a meaningful advancement. The combination therapy offers a viable option that not only extends progression-free survival but also maintains quality of life through manageable side effects.
Continued Commitment to Oncology Innovation
Verastem Oncology’s presence at the SGO 2026 Annual Meeting, including its exhibition booth and multiple presentations, underscores the company’s ongoing commitment to advancing cancer treatment. By focusing on therapies targeting the RAS/MAPK pathway, the company aims to address unmet needs in oncology, particularly in difficult-to-treat cancers.
The updated RAMP 201 data mark an important milestone as the therapy approaches its one-year anniversary since FDA approval, highlighting progress in delivering innovative and durable treatment options to patients.
The two-year follow-up results from the RAMP 201 trial demonstrate that the combination of avutometinib and defactinib provides sustained clinical benefit, durable responses, and a manageable safety profile in patients with recurrent low-grade serous ovarian cancer.
With strong efficacy across both KRAS-mutated and wild-type populations, consistent safety outcomes, and validated dosing strategies, the therapy represents a significant step forward in the management of this challenging disease.
As research continues and additional data emerge, this combination treatment is poised to play an increasingly important role in improving outcomes for patients with LGSOC.
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.
