TriangleNCT04625270 · CITED IN SOURCE DOCUMENTS
A Study of Avutometinib (VS-6766) v. Avutometinib (VS-6766) + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer With and Without a KRAS Mutation
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2025-01-29
This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy and in combination with defactinib in subjects with recurrent Low-Grade Serous Ovarian Cancer (LGSOC)
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Histologically proven LGSOC (ovarian, peritoneal) * Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease. * Measurable disease according to RECIST 1.1 * An Eastern Cooperative Group (ECOG) performance status ≤ 1. * Adequate organ function * Adequate recovery from toxicities related to prior treatments * Agreement to use highly effective method of contraceptive, if necessary Exclusion Criteria: * Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy * Co-existing high-grade ovarian cancer or another histology * History of prior malignancy with recurrence \<3 years from the time of enrollment * Major surgery within 4 weeks * Symptomatic brain metastases requiring steroids or other interventions * Known SARS-Cov2 infection (clinical symptoms) ≤28 days prior to first dose of study therapy * For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor * Active skin disorder that has required systemic therapy within the past year * History of rhabdomyolysis * Concurrent ocular disorders * Concurrent heart disease or severe obstructive pulmonary disease * Subjects with the inability to swallow oral medications
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- FEMALE
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- To determine the optimal regimen, either avutometinib(VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, for subsequent evaluation for efficacy in the Expansion Phase (Part B)
- intervention Names
- Drug: avutometinib (VS-6766)
- Drug: avutometinib (VS-6766) and defactinib
- label
- Part A
- type
- EXPERIMENTAL
- description
- To determine the efficacy of the optimal regimen identified from Part A
- intervention Names
- Drug: avutometinib (VS-6766)
- Drug: avutometinib (VS-6766) and defactinib
- label
- Part B
- type
- EXPERIMENTAL
- description
- To evaluate additional efficacy parameters for the optimal regimen identified in Part A.
- intervention Names
- Drug: avutometinib (VS-6766) and defactinib
- label
- Part C:
- type
- EXPERIMENTAL
- description
- To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib
- intervention Names
- Drug: avutometinib (VS-6766) and defactinib
- label
- Part D
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Part A
- Part B
- description
- avutometinib (VS-6766) monotherapy
- name
- avutometinib (VS-6766)
- type
- DRUG
- arm Group Labels
- Part A
- Part B
- Part C:
- Part D
- description
- avutometinib (VS-6766) and defactinib combination
- name
- avutometinib (VS-6766) and defactinib
- other Names
- avutometinib (VS-6766) and VS-6063
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- SEQUENTIAL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 225
- type
- ESTIMATED
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Confirmed overall response rate per RECIST 1.1
- measure
- Part A: Determine optimal regimen of avutometinib (VS-6766) monotherapy or in combination with defactinib
- time Frame
- From start of treatment to confirmation of response; 24 weeks
- description
- Confirmed overall response rate per RECIST 1.1
- measure
- Part B: To determine the efficacy of the optimal regimen identified from Part A
- time Frame
- From start of treatment to confirmation of response; 24 weeks
- description
- Confirmed overall response rate per RECIST 1.1
- measure
- Part C: To evaluate additional efficacy parameters for the optimal regimen identified in Part A
- time Frame
- From start of treatment to confirmation of response; 24 weeks
- description
- Confirmed ORR defined according to RECIST 1.1
- measure
- Part D:To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib
- time Frame
- From start of treatment to confirmation of response; 24 weeks
- secondary Outcomes
- description
- Proportioned subjects achieving a CR or PR as assess by the investigator
- measure
- Overall Response Rate as assessed by Investigator
- time Frame
- From start of treatment to confirmation of response; 24 weeks
- description
- From time of first response to PD as assessed by the BIRC
- measure
- Duration of Response (DOR)
- time Frame
- Time from the first documentation of response to first documentation of progressive disease or death due to any cause, greater than or equal to 6 months
- description
- CR+PR+stable disease
- measure
- Disease Control Rate (DCR)
- time Frame
- Greater than or equal to 8 weeks
- description
- From time of first dose of study intervention to PD or death for any cause
- measure
- Progression Free Survival (PFS)
- time Frame
- Up to 5 years
- description
- From time of first dose of study intervention to death
- measure
- Overall Survival (OS)
- time Frame
- Up to 5 years
Full study description
- brief Summary
- This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy and in combination with defactinib in subjects with recurrent Low-Grade Serous Ovarian Cancer (LGSOC)
- detailed Description
- This is a multicenter, randomized, open-label Phase 2 study designed to evaluate safety and tolerability and preliminary efficacy of avutometinib (VS-6766) versus avutometinib (VS-6766) in combination with defactinib in subjects with molecularly profiled recurrent LGSOC.
Source references
- references
- citation
- Banerjee SN, Van Nieuwenhuysen E, Aghajanian C, D'Hondt V, Monk BJ, Clamp A, Prendergast E, Oaknin A, Ring K, Colombo N, Holloway RW, Rodrigues M, Chon HS, Gourley C, Santin AD, Thaker PH, Gennigens C, Newman G, Salinas E, Youssoufian H, Moore KN, Lustgarten S, O'Malley DM, Van Gorp T, Grisham RN. Efficacy and Safety of Avutometinib +/- Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201. J Clin Oncol. 2025 Sep;43(25):2782-2792. doi: 10.1200/JCO-25-00112. Epub 2025 Jul 11.
- pmid
- 40644648
- type
- DERIVED
- citation
- McNamara B, Demirkiran C, Hartwich TMP, Bellone S, Manavella D, Mutlu L, Greenman M, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz PE, Coma S, Pachter JA, Santin AD. Preclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer. Gynecol Oncol. 2024 Apr;183:133-140. doi: 10.1016/j.ygyno.2024.01.028. Epub 2024 Mar 15.
- pmid
- 38493021
- type
- DERIVED
Source notices and limitations
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- 14 CLINICAL STUDIES The efficacy of AVMAPKI FAKZYNJA CO-PACK was evaluated in RAMP-201 (NCT04625270), an open-label, multicenter study that included 57 adult patients with measurable KRAS -mutated recurrent LGSOC. Patients were required to have received at le
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- Fakzynja Co-pack will be posted on <a href="https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm">Drugs@FDA</a>.</p><p>Efficacy was evaluated in RAMP-201 (NCT04625270), an open-label, multicenter trial that included 57 adult patients with measurable KRAS-mutated recurrent LGSOC. Patients were required to have received at lea
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- FDA grants accelerated approval to the combination of avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer
Preserved source evidence · Not medical advice