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

Sponsor
Verastem, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04620330
Collaborator
(none)
100
Enrollment
40
Locations
5
Arms
59
Anticipated Duration (Months)
2.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will assess the safety and efficacy of 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
Phase 2

Detailed Description

This is a multicenter, open-label Phase 2 study designed to evaluate safety and tolerability and efficacy of VS-6766 versus 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

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of 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 :
Dec 31, 2020
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1: VS-6766 monotherapy

in patients with NSCLC KRAS-G12V tumor

Drug: VS-6766
Monotherapy
Experimental: Arm 2: VS-6766 in combination with defactinib

in patients with a NSCLC KRAS-G12V tumor

Drug: VS-6766 and Defactinib
Combination therapy
Other Names:
  • VS-6766 and VS-6063

    		•
    Experimental: Arm 3: VS-6766 in combination with defactinib

    in patients with a NSCLC KRAS-other (non-G12V) tumor

    Drug: VS-6766 and Defactinib
    Combination therapy
    Other Names:
  • VS-6766 and VS-6063

    		•
    Experimental: Arm 4: VS-6766 in combination with defactinib

    in patients with a NSCLC BRAF-V600E tumor

    Drug: VS-6766 and Defactinib
    Combination therapy
    Other Names:
  • VS-6766 and VS-6063

    		•
    Experimental: Arm 5: VS-6766 in combination with defactinib

    in patients with a NSCLC BRAF-non-V600E tumor

    Drug: VS-6766 and Defactinib
    Combination therapy
    Other Names:
  • VS-6766 and VS-6063

    		•

    Outcome Measures

    Primary Outcome Measures

    1. To determine the optimal regimen, either VS-6766 monotherapy or VS-6766 in combination with defactinib, in KRAS-G12V NSCLC [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 VS-6766 in combination with defactinib in BRAF-MT NSCLC [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 [From start of treatment to confirmation of response; 24 weeks]

      Confirmed overall response rate per RECIST 1.1

    4. To determine the efficacy of VS-6766 in combination with defactinib in BRAF-MT NSCLC [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 [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 [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 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) [Greater than or equal to 8 weeks]

      CR and PR stable disease as assessed by the IRC

    5. Progression Free Survival (PFS) [Up to 5 years]

      From the time of first dose of study intervention to PD or death from any cause

    6. Overall Survival (OS) [Up to 5 years]

      From time of first dose of study intervention to death

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 City of Hope Duarte California United States 91010
    2 University of Colorado Hospital Aurora Colorado United States 80045
    3 Rocky Mountain Cancer Centers Lone Tree Colorado United States 80124
    4 Georgetown University Medical Center Washington District of Columbia United States 20007
    5 Florida Cancer Specialists Fort Myers Florida United States 33908
    6 Florida Cancer Specialists Saint Petersburg Florida United States 33705
    7 Emory University School of Medicine Atlanta Georgia United States 30322
    8 Northwestern University Chicago Illinois United States 60611
    9 University of Chicago Medical Center-Duchossois Center for Advanced Medicine Chicago Illinois United States 60637
    10 Illinois Cancer Specialists Niles Illinois United States 60714
    11 Hematology/Oncology Clinic, LLP Baton Rouge Louisiana United States 70809
    12 Maryland Oncology Hematology P.A Columbia Maryland United States 21044
    13 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    14 Henry Ford Cancer Institute/Henry Ford Health System Detroit Michigan United States 48202
    15 Washington University School of Medicine Saint Louis Missouri United States 63110
    16 Hackensack University Medical Center Hackensack New Jersey United States 07601
    17 Northwell Health-Monter Cancer Center Lake Success New York United States 11042
    18 Zangmeister Cancer Center Columbus Ohio United States 43219
    19 Northwest Cancer Specialists, P.C. Portland Oregon United States 97213
    20 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    21 Univ. of Pittsburgh Med Center Pittsburgh Pennsylvania United States 15232
    22 Chattanooga Oncology Hematology Assoc. Chattanooga Tennessee United States 037404
    23 Tennessee Oncology Nashville Tennessee United States 37203
    24 Texas Oncology Dallas Texas United States 75246
    25 Texas Oncology Ft Worth Cancer Center Fort Worth Texas United States 76104
    26 Texas Oncology Grapevine Texas United States 76051
    27 MD Anderson Cancer Center Houston Texas United States 77030
    28 Virginia Cancer Specialists, PC Fairfax Virginia United States 22031
    29 Centre Leon Berard Lyon France 69373
    30 Hopital Cochin Paris France 75014
    31 Institute De Cancerologie De L'Ouest Site Paul Papin Oncologie Medicale Saint-Herblain France 44805
    32 Cancerologie Gustave Roussy - Cancer Medicine Villejuif France 94800
    33 Klinikum Chemnitz gGmbH Chemnitz Germany 09116
    34 Universitatsklinkum Leipzig Leipzig Germany 04103
    35 Azienda Ospedaliera Universitaria Orbassano Torino Italy 10043
    36 Centro Ricerche Cliniche di Verona Verona Italy 37134
    37 Hospital Clinic de Barcelona Barcelona Spain
    38 Complejo Hospitalario Universiario a Coruna Teresa Coruña Spain 15006
    39 Universitario de Teatinos Málaga Spain 29010
    40 Hospital Universitario Virgen de la Macarena Sevilla Spain 41009

    Sponsors and Collaborators

    • Verastem, Inc.

    Investigators

    • Principal Investigator: Ross Camidge, MD, PhD, University of Colorado, Denver
    • Study Director: Hagop Youssoufian, MD, Verastem, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Verastem, Inc.
    ClinicalTrials.gov Identifier:
    NCT04620330
    Other Study ID Numbers:
    • VS-6766-202
    First Posted:
    Nov 6, 2020
    Last Update Posted:
    Jul 20, 2022
    Last Verified:
    Jul 1, 2022
    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:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung

    Study Results

    No Results Posted as of Jul 20, 2022