Avutometinib Plus Defactinib Shows Lasting Benefit in LGSOC

Dr. Rachel N. Grisham presented findings at the 2026 Society of Gynecologic Oncology Annual Meeting showing that the combination of avutometinib and defactinib led to long-lasting responses in patients with low-grade serous ovarian cancer, a rare form of ovarian cancer that can be difficult to treat.

How effective was avutometinib plus defactinib in low-grade serous ovarian cancer?

In the phase 2 RAMP 201 trial, the combination helped shrink or control cancer in many patients.

Among 109 patients, 31% experienced tumor shrinkage, including 2% whose cancer disappeared completely. In addition, 57% of patients had stable disease, meaning their cancer did not grow.

This means that most patients experienced some level of disease control, which is important because this type of ovarian cancer often grows slowly but can be hard to treat with standard therapies.

The responses also lasted for a long time. The median duration of response was 31.1 months, meaning that for many patients, the treatment continued to work for more than 2 years.

At 12 months, 71% of patients who responded to treatment were still seeing benefit, and at 24 months, 56% continued to respond.

The treatment also delayed cancer growth. The median time before the cancer worsened was 12.9 months. At 12 months, 58% of patients had not experienced disease progression, and at 24 months, 25% remained progression-free.

What do these results suggest for patients with this type of ovarian cancer?

Low-grade serous ovarian cancer can be challenging to treat, especially after prior therapies have stopped working.

The results from this study show that this combination may help keep the cancer under control for a longer period of time, which may allow patients to stay on the same treatment longer and delay the need for other therapies.

Some patients remained on treatment for more than a year, and in many cases, the responses lasted well beyond that, suggesting the treatment may provide long-term benefit for certain patients.

How was the RAMP 201 trial conducted?

The RAMP 201 trial included patients with recurrent low-grade serous ovarian cancer who had previously received platinum-based chemotherapy. Patients were required to have measurable disease, meaning their tumors could be tracked during treatment.

Patients received avutometinib together with defactinib on a schedule of 3 weeks on treatment followed by 1 week off.

The study evaluated how well the treatment worked by measuring tumor response, how long responses lasted, how long patients lived without their cancer worsening and safety.

The median age of patients in the study was 54 years, and many had received several prior treatments before joining the trial.

Did some patients respond better than others?

The study looked at patients with and without a KRAS mutation, a genetic change found in some cancers.

Among patients with KRAS-mutated disease, 44% experienced tumor shrinkage, and responses lasted a median of 31.1 months. The median time before cancer worsened in this group was 19.6 months.

Among patients without this mutation, 17% experienced tumor shrinkage, and the median duration of response was 12.0 months.

These results suggest that the treatment may work better in patients with certain tumor characteristics, but some benefit was seen in both groups.

What side effects were reported with avutometinib plus defactinib?

The side effects seen with the combination were similar to those reported earlier in the study, and no new safety concerns were identified.

The most common side effects included nausea, diarrhea, swelling and rash. Some patients also had changes in blood test results, including increased levels of a muscle-related enzyme.

More serious side effects were less common but included higher levels of this enzyme, diarrhea and anemia.

Many patients needed dose adjustments to help manage side effects. Treatment was temporarily stopped in 84% of patients due to side effects, and 37% required a dose reduction.

About 12% of patients stopped treatment due to side effects.

Importantly, no deaths were reported as a result of treatment.

Researchers noted that side effects were generally manageable and that the treatment could be given over a long period of time for many patients.

References

1. Rachel N. Grisham, MD, et al. “Long-term efficacy and safety of avutometinib plus defactinib in patients with recurrent low-grade serous ovarian cancer: results from ENGOT-ov60/GTG-UK/GOG-3052.” Presented at the 2026 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
2. U.S. Food and Drug Administration. “FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer.” Published May 8, 2025. Accessed April 10, 2026.
3. ClinicalTrials.gov. “A study of avutometinib versus avutometinib plus defactinib in recurrent low-grade serous ovarian cancer with and without a KRAS mutation (RAMP 201).” Updated January 29, 2025. Accessed April 10, 2026.

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