The combination of avutometinib and defactinib in treating recurrent low-grade serous ovarian cancer - a plain language summary of the Phase II clinical trial ENGOT-OV60/GOG-3052/RAMP 201

Sep 28, 2026

Plain Language Summary of publication describing the Phase II ENGOT-OV60/GOG-3052/RAMP 201 clinical trial in recurrent low-grade serous ovarian cancer (LGSOC). The study assessed avutometinib alone versus combination therapy with defactinib, including a lower-dose combination, in patients whose cancer recurred or persisted after surgery and chemotherapy. All participants were tested for the non-hereditary KRAS somatic mutation. The primary endpoint was confirmed objective response rate, alongside monitoring adverse events and other efficacy measures.

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CategoryHealthcare

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Future ONCOLOGY Plain Language Summary of Publication The combination of avutometinib and defactinib in treating recurrent low-grade serous ovarian cancer: a plain language summary of the Phase II clinical trial ENGOT-OV60/GOG-3052/RAMP 201 Susana N. Banerjeea, Els Van Nieuwenhuysenb, Carol Aghajanianc,d, Véronique D’Hondte, Bradley J. Monkf, Andrew Clampg, Emily Prendergasth, Ana Oaknini, Kari Ringj, Nicoletta Colombok, l, Robert W. Hollowaym, Manuel Rodriguesn,o, Hye Sook Chonp, Charlie Gourleyq, Alessandro D. Santinr, Premal H. Thakers, Christine Gennigenst, Gregg Newmanu, Erin Salinasv, Hagop Youssoufianw, Kathleen N. Moorex, Stephanie Lustgartenw, David M. O’Malleyy, Toon Van Gorpb & Rachel N. Grishamc,d Author affiliations can be found at the end of this article First draft submitted: 3 October 2025; Accepted for publication: 21 November 2025 Where can I find the original article on which this summary is based? The original article is titled ‘Efficacy and safety of avutometinib ± defactinib in recurrent low-grade serous ovarian cancer: Primary analysis of ENGOT-OV60/GOG-3052/RAMP 201,’ and it can be read for free at: [https://doi.org/10.1200/JCO-25-001](https://doi.org/10.1200/JCO-25-001)12. What is this summary about? How to say (download PDF and double click sound icon to play sound) ... • Avutometinib: Uh-VU-toe-MEH-ti-nib • Defactinib: De-FAK-ti-nib This plain language summary describes the results of the ENGOT-OV60/ GOG-3052/RAMP 201 clinical study, which were published in 2025. The Phase II study evaluated treatments for patients with a rare type of ovarian cancer, low-grade serous ovarian cancer (LGSOC). The study specifically involved those whose cancer came back or persisted, despite already having surgery and previous chemotherapy. Researchers investigated the effect of avutometinib on its own and in combination with defactinib to see which treatment would be more effective and to determine if both treatments were safe. They also investigated the combination of a lower dose of avutometinib with defactinib. All trial participants were tested for a specific KRAS genetic mutation (non-hereditary, also called somatic). The main goal of the study was to determine the confirmed objective response rate of each treatment. This is the percentage of patients whose cancer shrinks by at least 30% after treatment and maintains this shrinkage for at least 2 months. The study also closely monitored for any adverse events associated with each treatment and looked at other measures of treatment effectiveness. What were the results? The percentage of patients with an objective response was 31% in the combination treatment group and 17% in the avutometinibonly group. Amongst patients receiving the combination, the objective response rate was 44% in the group of participants with a KRAS mutation and 17% in the group without a KRAS mutation. The lower dose of avutometinib used in combination with defactinib was not as effective as the standard dose. In the standard dose combination treatment group, most adverse events were not severe (categorized as grade 1 or 2 on a scale of 0 to 5) and were managed with dose holds or dose reductions. The most frequent adverse events reported were nausea, increased creatine phosphokinase (CPK), diarrhea, peripheral edema, andrash. A total of 10% of participants discontinued treatment due to adverse events. 10. 1080/14796694 .2025. 2595130 © 2025 The Author(s) . Published by Informa UK Limited, trading as Taylor & Francis Group This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on w

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What was the Phase II trial designed to evaluate?

The trial evaluated avutometinib alone and in combination with defactinib, including a lower-dose combination, to determine effectiveness and safety for recurrent LGSOC patients after surgery and prior chemotherapy.

How did the objective response rates compare between treatments?

Objective response was 31% for the combination group and 17% for the avutometinib-only group. Within the combination group, response was 44% for participants with a KRAS mutation and 17% for those without.

What adverse events were reported and how were they managed?

Most adverse events were not severe (grades 1–2) and were managed with dose holds or dose reductions. The most frequent events included nausea, increased creatine phosphokinase, diarrhea, peripheral edema, and rash, and 10% discontinued due to adverse events.

Sep 28, 2026

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