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A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer (RAMP202)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04620330
Recruitment Status : Recruiting
First Posted : November 6, 2020
Last Update Posted : December 27, 2022
Sponsor:
Information provided by (Responsible Party):
Verastem, Inc.

Study Description
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Brief Summary:
This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy or VS-6766 in combination with defactinib in subjects with recurrent Non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer KRAS Activating Mutation Drug: avutometinib (VS-6766) Drug: avutometinib (VS-6766) and Defactinib Phase 2

Detailed Description:
This is a multicenter, open-label Phase 2 study designed to evaluate safety and tolerability and efficacy of avutometinib (VS-6766) versus avutometinib (VS-6766) in combination with defactinib in subjects with KRAS and BRAF mutant NSCLC following treatment with an appropriate platinum-based regimen and an approved immune checkpoint inhibitor (CPI).
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Avutometinib (VS-6766) (Dual RAF/MEK Inhibitor) as a Single Agent and In Combination With Defactinib (FAK Inhibitor) in Recurrent KRAS-Mutant (KRAS-MT) and BRAF-Mutant (BRAF-MT) Non-Small Cell Lung Cancer (NSCLC) (RAMP 202)
Actual Study Start Date : December 31, 2020
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1: avutometinib (VS-6766) monotherapy
in patients with NSCLC KRAS-G12V tumor
 Drug: avutometinib (VS-6766)
Monotherapy
Experimental: Arm 2: avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC KRAS-G12V tumor
 Drug: avutometinib (VS-6766) and Defactinib
Combination therapy
Other Name: avutometinib (VS-6766) and VS-6063
Experimental: Arm 3: avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC KRAS-other (non-G12V) tumor
 Drug: avutometinib (VS-6766) and Defactinib
Combination therapy
Other Name: avutometinib (VS-6766) and VS-6063
Experimental: Arm 4: avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC BRAF-V600E tumor
 Drug: avutometinib (VS-6766) and Defactinib
Combination therapy
Other Name: avutometinib (VS-6766) and VS-6063
Experimental: Arm 5:avutometinib (VS-6766) in combination with defactinib
in patients with a NSCLC BRAF-non-V600E tumor
 Drug: avutometinib (VS-6766) and Defactinib
Combination therapy
Other Name: avutometinib (VS-6766) and VS-6063


Outcome Measures
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Primary Outcome Measures :
  1. To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC [ Time Frame: From start of treatment to confirmation of response; 24 weeks ]
    Confirmed overall response rate per RECIST 1.1

  2. To evaluate the initial efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC [ Time Frame: From start of treatment to confirmation of response; 24 weeks ]
    Confirmed overall response rate per RECIST 1.1

  3. To determine efficacy in KRAS-other (non-G12V) NSCLC [ Time Frame: From start of treatment to confirmation of response; 24 weeks ]
    Confirmed overall response rate per RECIST 1.1

  4. To determine the efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC [ Time Frame: From start of treatment to confirmation of response; 24 weeks ]
    Confirmed overall response rate per RECIST 1.1


Secondary Outcome Measures :
  1. To characterize the safety and toxicity profile of VS-6766 as a monotherapy and in combination with defactinib in KRAS-MT NSCLC and in BRAF-MT NSCLC [ Time Frame: 24 weeks ]
    Adverse events (AEs), serious AEs (SAEs), vital signs, physical examinations, clinical laboratory values, and tolerability (dose interruptions/reductions)

  2. Overall Response Rate per RECIST 1.1 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

  3. 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 ]
    Time of first response to PD as assessed by the IRC

  4. Disease Control Rate (DCR) [ Time Frame: Greater than or equal to 8 weeks ]
    CR and PR stable disease as assessed by the IRC

  5. Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
    From the time of first dose of study intervention to PD or death from any cause

  6. Overall Survival (OS) [ Time Frame: Up to 5 years ]
    From time of first dose of study intervention to death


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects ≥ 18 years of age
  • Histologic or cytologic evidence of NSCLC
  • Known KRAS or BRAF mutation
  • The subject must have received appropriate prior therapy
  • 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

Exclusion Criteria:

  • Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
  • History of prior malignancy, with the exception of curatively treated malignancies
  • Major surgery within 4 weeks (excluding placement of vascular access)
  • History of treatment with a direct and specific inhibitor of MEK, KRAS or BRAF except for treatment of BRAF V-600E mutant NSCLC
  • Exposure to strong CYP2C9 and CYP3A4 inhibitors or inducers within 7 days prior to the first dose and during the course of therapy
  • Symptomatic brain metastases requiring steroids or other local interventions.
  • Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
  • Active skin disorder that has required systemic therapy within the past 1 year
  • History of rhabdomyolysis
  • Concurrent ocular disorders
  • Concurrent heart disease or severe obstructive pulmonary disease
  • Subjects with the inability to swallow oral medications
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04620330


Contacts
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Contact: Verastem Call Center 781-292-4204 clinicaltrials@verastem.com

Locations
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Sponsors and Collaborators
Verastem, Inc.
Investigators
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Principal Investigator: Ross Camidge, MD, PhD University of Colorado, Denver
Study Director: MD Verastem Verastem, Inc.
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Verastem, Inc.
ClinicalTrials.gov Identifier: NCT04620330    
Other Study ID Numbers: VS-6766-202
First Posted: November 6, 2020    Key Record Dates
Last Update Posted: December 27, 2022
Last Verified: December 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Verastem, Inc.:
NSCLC
KRAS-G12V
G12V
 BRAF
V600E
KRAS
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
 Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms