A New Targeted Treatment for Recurrent Low-Grade Serous Ovarian Cancer
For women living with low-grade serous ovarian cancer (LGSOC), recurrence after initial treatment is a difficult reality, and for years there have been no FDA-approved therapies designed specifically for this cancer.¹ In May 2025, that changed. The FDA granted accelerated approval for the Avmapki™ / Fakzynja™ Co-Pack, a combination of avutometinib and defactinib, for adults with KRAS-mutant recurrent LGSOC who have already had systemic therapy.² This is the first targeted treatment ever approved for this group of patients.³
How the Drug Combo Works
Avutometinib targets the MAPK signaling pathway, which is often overactive when KRAS is mutated.⁴ Defactinib blocks focal adhesion kinase (FAK), which helps cancer cells survive and spread.⁵ Working together, the drugs attack cancer growth from two angles, making tumor cells more vulnerable.⁶
Clinical Trial Evidence: RAMP 201
The FDA’s approval was based on results from the RAMP 201 Phase 2 trial (ENGOT-ov60 / GOG-3052).⁷ In this study of 109 patients with recurrent LGSOC, the subgroup of 57 patients whose tumors carried KRAS mutations showed a 44% response rate, meaning nearly half experienced measurable tumor shrinkage.⁸ In all patients, the response rate was 31%, and the median duration of response was over 31 months.⁹ The treatment was generally manageable, with side effects such as nausea, fatigue, rash, and mild liver test changes leading only a small number of patients to stop therapy.¹⁰
Why Biomarker Testing Is Essential
This new therapy works only if the tumor has a KRAS mutation.¹¹ About 30% of LGSOC tumors carry this mutation, so genomic (molecular) testing is critical to identify who qualifies.¹² Without testing, patients may miss the chance to benefit from the drug or be exposed unnecessarily if their tumor lacks the mutation.¹³
Future Clinical Development
Because the approval was accelerated, it depends on confirmation in a larger trial. The ongoing RAMP 301 Phase 3 trial is comparing the Avmapki / Fakzynja combo to standard treatments.¹⁴ If it confirms longer disease control, the therapy could become a new standard of care.¹⁵ Researchers are also exploring whether this strategy can extend beyond ovarian cancer into other KRAS-driven tumors.¹⁶
What This Means for Patients
For patients with KRAS-mutant recurrent LGSOC, this is the first therapy proven to shrink tumors and control disease in a meaningful way.¹⁷ While it is not a cure, it represents real hope in an area with few options. Oncologists now must integrate biomarker testing into routine care and consider this drug for eligible patients.
Conclusion: Navexio’s Role
At Navexio, we help patients and families understand whether advanced molecular testing is appropriate, interpret complex results, and connect them to new therapies or clinical trials. The approval of Avmapki / Fakzynja shows why precision oncology matters: matching the right treatment to the right biology. For anyone navigating recurrent ovarian cancer—or other cancers with emerging targeted options—Navexio is here to guide every step of the way.
References
FDA Approves First Targeted Therapy for KRAS-Mutant Recurrent Low-Grade Serous Ovarian Cancer. FDA, 2025.
Verastem Oncology. Press Release: FDA Approval of Avmapki / Fakzynja Co-Pack, 2025.
The ASCO Post. FDA Approves Doublet for KRAS-Mutated, Recurrent LGSOC, 2025.
Avutometinib (Drug Mechanism). Wikipedia, 2025.
Defactinib (Drug Mechanism). Wikipedia, 2025.
OncLive. Avutometinib/Defactinib Expands Treatment Options, 2025.
Verastem Oncology. RAMP 201 Phase 2 Data Publication, 2025.
Verastem Oncology. RAMP 201 Trial Results, 2025.
CancerNetwork. Avutometinib Combo Yields Responses in LGSOC, 2025.
Targeted Oncology. Avutometinib + Defactinib Gains FDA Approval, 2025.
OncLive. Accelerated Approval Establishes Role of Avutometinib/Defactinib, 2025.
Drugs.com. Avmapki Fakzynja Co-Pack Drug Snapshot, 2025.
OncLive. The Role of Biomarker Testing in KRAS-Mutant Ovarian Cancer, 2025.
ClinicalTrials.gov. NCT05683344 (RAMP 301 Phase 3 Trial).
PubMed. ENGOT-ov81 / GOG-3097 RAMP 301 Trial Overview, 2025.
Verastem Oncology. FRAME Study & Future Development, 2024.
CancerNetwork. FDA Approval Signals “Exciting Time” in KRAS-Mutant LGSOC, 2025.