A Study of Avutometinib (VS-6766) v. Avutometinib (VS-6766) + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer With and Without a KRAS Mutation (RAMP 201)

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ClinicalTrials.gov Identifier: NCT04625270

Recruitment Status : Active, not recruiting

First Posted : November 12, 2020

Last Update Posted : March 12, 2024

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborators:

European Network of Gynaecological Oncological Trial Groups (ENGOT)

GOG Foundation

Information provided by (Responsible Party):

Verastem, Inc.

Tracking Information

First Submitted Date ^ICMJE

November 5, 2020

First Posted Date ^ICMJE

November 12, 2020

Last Update Posted Date

March 12, 2024

Actual Study Start Date ^ICMJE

December 21, 2020

Estimated Primary Completion Date

December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ]
Confirmed overall response rate per RECIST 1.1
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 ]
Confirmed overall response rate per RECIST 1.1
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 ]
Confirmed overall response rate per RECIST 1.1
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 ]
Confirmed ORR defined according to RECIST 1.1

Original Primary Outcome Measures ^ICMJE

Part A: Determine optimal regimen of VS-6766 monotherapy or in combination with defactinib [ Time Frame: From start of treatment to confirmation of response; 24 weeks ]
Confirmed overall response rate per RECIST 1.1
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 ]
Confirmed overall response rate per RECIST 1.1

Change History

Current Secondary Outcome Measures ^ICMJE

Overall Response Rate as assessed by Investigator [ Time Frame: From start of treatment to confirmation of response; 24 weeks ]
Proportioned subjects achieving a CR or PR as assess by the investigator
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 ]
From time of first response to PD as assessed by the BIRC
Disease Control Rate (DCR) [ Time Frame: Greater than or equal to 8 weeks ]
CR+PR+stable disease
Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
From time of first dose of study intervention to PD or death for any cause
Overall Survival (OS) [ Time Frame: Up to 5 years ]
From time of first dose of study intervention to death

Original Secondary Outcome Measures ^ICMJE

Overall Response Rate as assessed by Investigator [ Time Frame: From start of treatment to confirmation of response; 24 weeks ]
Proportioned subjects achieving a CR or PR as assess by the investigator
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 ]
From time of first response to PD as assessed by the IRC
Disease Control Rate (DCR) [ Time Frame: Greater than or equal to 8 weeks ]
CR+PR+stable disease as assessed by the IRC
Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
From time of first dose of study intervention to PD or death for any cause
Overall Survival (OS) [ Time Frame: Up to 5 years ]
From time of first dose of study intervention to death

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

A Study of Avutometinib (VS-6766) v. Avutometinib (VS-6766) + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer With and Without a KRAS Mutation

Official Title ^ICMJE

A Phase 2 Study of Avutometinib (VS-6766) (Dual RAF/MEK Inhibitor) Alone and In Combination With Defactinib (FAK Inhibitor) in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC)

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.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Low Grade Ovarian Serous Adenocarcinoma
Ovarian Cancer

Intervention ^ICMJE

Drug: avutometinib (VS-6766)
avutometinib (VS-6766) monotherapy
Drug: avutometinib (VS-6766) and defactinib
avutometinib (VS-6766) and defactinib combination

Other Name: avutometinib (VS-6766) and VS-6063

Study Arms ^ICMJE

Experimental: Part A
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)
Interventions:
- Drug: avutometinib (VS-6766)
- Drug: avutometinib (VS-6766) and defactinib
Experimental: Part B
To determine the efficacy of the optimal regimen identified from Part A
Interventions:
- Drug: avutometinib (VS-6766)
- Drug: avutometinib (VS-6766) and defactinib
Experimental: Part C:
To evaluate additional efficacy parameters for the optimal regimen identified in Part A.

Intervention: Drug: avutometinib (VS-6766) and defactinib
Experimental: Part D
To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib

Intervention: Drug: avutometinib (VS-6766) and defactinib

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Estimated Enrollment ^ICMJE

225

Original Estimated Enrollment ^ICMJE

100

Estimated Study Completion Date ^ICMJE

December 2026

Estimated Primary Completion Date

December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender ^ICMJE

Sexes Eligible for Study:

Female

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Belgium, Canada, France, Italy, Spain, United Kingdom, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04625270

Other Study ID Numbers ^ICMJE

VS-6766-201
GOG-3052 ( Other Identifier: The GOG Foundation, Inc. )
ENGOT-ov60 ( Other Identifier: ENGOT )

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Not Provided

Current Responsible Party

Verastem, Inc.

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Verastem, Inc.

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

European Network of Gynaecological Oncological Trial Groups (ENGOT)
GOG Foundation

Investigators ^ICMJE

Principal Investigator:	Susana Banerjee, MBBS,MA,PhD	European Network of Gynaecological Oncological Trial Groups (ENGOT)
Principal Investigator:	Rachel Grisham, MD	GOG Foundation
Study Director:	MD Verastem	Verastem, Inc.

PRS Account

Verastem, Inc.

Verification Date

March 2024

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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