The FDA has granted accelerated approval to a new combination therapy-avutometinib plus defactinib (Avmapki Fakzynja Co-pack)-for adults with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have already received systemic therapy.
What Does This Mean for Patients?
- First Approved Option for This Subtype: This is the first FDA-approved treatment specifically for patients with recurrent KRAS-mutated LGSOC, a rare and difficult-to-treat form of ovarian cancer.
- Who Is Eligible? Adult patients whose cancer has returned and who have previously tried at least one systemic therapy can now access this new combination treatment.
How Effective Is the New Treatment?
- Impressive Response Rates: In the RAMP-201 clinical trial, 44% of patients with KRAS-mutated LGSOC saw their tumors shrink (overall response rate), with some responses lasting from 3.3 months up to 31.1 months.
- Tumor Shrinkage: Most patients experienced some degree of tumor reduction, and the median progression-free survival (the time during and after treatment when the cancer does not get worse) was over one year for both KRAS-mutated and wild-type patients.
- Better Than Previous Therapies: Only 8.7% of patients responded to their previous treatment, compared to 43.5% who responded to avutometinib plus defactinib in the trial.
Common Side Effects: The most frequently reported side effects (in at least 25% of patients) included:
- Muscle enzyme increases
- Nausea
- Fatigue
- Rash
- Diarrhea
- Muscle and joint pain
- Swelling (edema)
- Changes in blood counts and liver enzymes
- Abdominal pain and digestive issues
- Skin changes and visual disturbances
Most side effects were manageable, and the discontinuation rate due to side effects was low.
About Avutometinib plus Defactinib (Avmapki Fakzynja Co-pack)
To get better and longer-lasting results, combination therapies are designed to overcome key resistance mechanisms, offering the potential for deeper and more durable responses. For patients with cancers driven by KRAS mutations, such as certain ovarian and lung cancers, these combination therapies could provide new hope, especially when other treatments have stopped working.
- Avutometinib targets the RAF/MEK part of the RAS pathway (vertical blockade).
- Defactinib targets FAK, a different pathway cancer can use to survive (parallel inhibition).
- By combining these two drugs, the treatment attacks cancer from multiple angles, making it harder for cancer cells to adapt and survive.
What’s Next?
- Confirmatory Trials Ongoing: The RAMP-301 phase 3 trial is underway to further confirm the benefits of this combination and potentially expand its use to more patients, including those without KRAS mutations.
- Availability: With this approval, patients in the US with this rare cancer subtype now have a new, targeted option that was not available before.
If you have KRAS-mutated recurrent low-grade serous ovarian cancer, talk to your oncologist about whether this new therapy might be right for you.
More Reading
Treatment and Management of Ovarian Cancer
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Reference:
Banerjee SN, Nieuwenhuysen EV, Santin A, et al. Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC): A Subgroup Analysis of ENGOT-ov60/GOG3052/RAMP 201 Part A. Gynecologic Oncology. 2024;190:S55 – S5.
