The RAMP 301 Clinical Trial (NCT06072781) for low-grade serous ovarian cancer (LGSOC) has opened.
The Phase 3 trial is evaluating the novel combination treatment Avutometinib and Defactinib against the standard of care in people whose low-grade serous ovarian cancer has come back (recurred) after treatment.
Avutometinib is a MEK/BRAF inhibitor, and Defactinib is a FAK inhibitor. Last year the phase 2 clinical trial RAMP 201 testing this combination found an objective response rate (ORR) of 45% in recurrent low-grade serous ovarian cancer.
For context, this compares favourably to trametinib, which outperformed standard of care with an ORR of 26% in its Phase 2/3 clinical trial published in 2022. Trametinib has since been listed in the US NCCN Ovarian Cancer Guidelines and funded in the United Kingdom for recurrent LGSOC.
Verastem Oncology recently received Orphan Drug Designation from the FDA to help accelerate the Avutometinib and Defactinib combination treatment’s path to approval.
Currently, all prescribed treatments for low-grade serous ovarian cancer are used off-label (e.g. letrozole), or have broad ovarian cancer approval (e.g. carboplatin chemotherapy). There are no FDA approved treatments for LGSOC.
Participants in the RAMP 301 trial will be randomly allocated to one of two treatment arms, receiving either Avutometinib with Defactinib, or an ‘Investigators Choice of Treatment’. Participants in the ‘Investigators Choice of Treatment’ arm will be given their doctor’s choice of pegylated liposomal doxorubicin or paclitaxel or topotecan or anastrozole, or letrozole, which are standard treatments used in recurrent low-grade serous ovarian cancer treatment.
The trial is a ‘crossover’ assignment. This means that anyone in the clinical trial whose cancer progresses on treatment will be switched to the other treatment arm, so people who don’t initially receive Avutometinib with Defactinib will still have the opportunity to try it if their cancer progresses.
“Clinical trials are an opportunity to have advanced access to treatments while helping inform treatment choices for women in the future.
The success of this clinical trial would send a strong signal to the pharmaceutical industry that investment in rare ovarian cancers is both possible and desirable.
We hope Avutometinib and Defactinib will be the first of many new treatments for low-grade serous ovarian cancer.”
Jane Ludemann, Founder of the Low Grade Serous Ovarian Cancer Initiative
Update: as of 29 October 2024 the trial is recruiting in Australia, Canada, France, Italy, Spain, the United Kingdom and United States of America. Further countries are planned.
For up to date information on clinical trial sites visit clinicaltrials.gov.
Eligibility:
The eligibility criteria for the trial include people with:
- Recurrent low-grade serous cancer (ovarian, fallopian tube, or peritoneal).
- Aged 18 years or older.
- Have had progression or recurrence after at least one prior systemic treatment for metastatic disease.
- Measurable cancer on scans according to the RECIST v1.1 guidelines.
- Being in otherwise adequate health.
- Previous MEK inhibitor use is not an exclusion criteria so long as there were no life threatening complications and the person has not received avutometinib before.
People will not be able to participate in the trial if they have:
- Co-existing high-grade serous ovarian cancer (but borderline tumours are acceptable).
- Symptomatic brain metastases.
- Previous treatment with avutometinib, defactinib, or other FAK inhibitors.
- An active skin condition in the past year that required systemic therapy.
- A history of medically significant rhabdomyolysis, heart disease or severe obstructive pulmonary disease.
- Inability to swallow oral medication.
This is not an exhaustive list. The full list of criteria and exclusion clauses can be found at clinicaltrials.gov
Further Information:
- Interpreting Results From RAMP 201: Avutometinib +/- Defactinib in Recurrent LGSOC – Onc Live Interview with Dr O’Malley – 3 November 2023
- RAF/MEK and FAK Inhibitor Combo Effective in Low-Grade Serous Ovarian Cancer — Impressive overall response rate with avutometinib-defactinib in RAMP 201 trial – coverage of the International Gynaecologic Cancer Society Annual Meeting presentation by MedPage Today – 5 November 2023
- Verastem Oncology Presents Positive Updated RAMP 201 Data for Avutometinib and Defactinib Combination in Recurrent Low-Grade Serous Ovarian Cancer at the International Gynecologic Cancer Society (IGCS) 2024 Annual Meeting – Verastem press release – 17 October 2024
- Clinical Trial Offers New Hope To Women – UK news article and video featuring Dr Bannerjee and low-grader Katie – 19 October 2024
