Avutometinib/Defactinib May be a New SOC in Low-Grade Serous Ovarian Cancer

In an interview with CancerNetwork^®, Susana N. Banerjee, MD, discussed the impact results from the phase 2 RAMP 201 trial (NCT04625270) may have on the low-grade serous ovarian cancer space. In particular, she stated that she is hopeful the combination will eventually receive an approval in this indication because its rare nature.

The trial evaluated avutometinib or avutometinib and defactinib in patients with low-grade serous ovarian cancer with and without KRAS mutations. In the single-agent arm, the confirmed overall response rates (ORR) in the KRAS mutant, KRAS wild-type, and overall populations, respectively, were 13%, 6%, and 10%. The corresponding rates in the combination arm were 60%, 29%, and 45%, respectively.

She also highlighted that there are plans to further assess the combination in a phase 3 study in addition to presenting more data from the phase 2 RAMP 201 study after additional patients have enrolled. Banerjee is a consultant medical oncologist and research lead for The Royal Marsden NHS Foundation Trust Gynaecology Unit at the Institute of Cancer Research in London and presented data from the trial at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

Transcript:

I’m very encouraged by these initial interim results. What this has done is lead to the selection of the combination of avutometinib and defactinib as the go-forward regimen in patients with recurrent low-grade serous ovarian cancer. This is based on the response rates that I’ve reported in previously treated recurrent, low-grade serous ovarian cancer regardless of the KRAS mutation status, and the manageable safety profile so far with relatively low rates of dose reductions and discontinuation.

We presented the initial interim results, and we will present [additional data] when we have more women enrolled in this study. The key next step is going forward with a phase 3 randomized clinical trial. I very much hope that the regulatory authorities recognize this activity in a rare form of ovarian cancer [for which] our current approved therapies have lower activity. We need more results from this clinical trial, and also going forward with further clinical trials. I very much hope that [by] working together globally with patients who have low-grade serous ovarian cancer, we may be able to set a new standard of care.

Reference

Banerjee S, Ring KL, Nieuwenhuysen EV, et al. Initial efficacy and safety results from ENGOT-ov60/GOG-3052/RAMP 201: A phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC). J Clin Oncol. 2023;41(suppl 16):5515. doi:10.1200/JCO.2023.41.16_suppl.5515