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Trial record 1 of 1 for:    NCT05375994
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Study of VS-6766 + Adagrasib in KRAS G12C NSCLC Patients (RAMP204)

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ClinicalTrials.gov Identifier: NCT05375994
Recruitment Status : Recruiting
First Posted : May 17, 2022
Last Update Posted : November 28, 2022
Sponsor:
Collaborator:
Mirati Therapeutics Inc.
Information provided by (Responsible Party):
Verastem, Inc.

Brief Summary:
This study will assess the safety and efficacy of Avutometinib (VS-6766) in combination with adagrasib in patients with G12C Non-Small Cell Lung Cancer (NSCLC) who have been exposed to prior G12C inhibitor and experienced progressive disease.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer KRAS Activating Mutation Advanced Cancer Metastatic Cancer Malignant Neoplasm of Lung Malignant Neoplastic Disease Drug: Avutometinib (VS-6766) and adagrasib Phase 1 Phase 2

Detailed Description:
This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety, tolerability and efficacy of Avutometinib (VS-6766) in combination with adagrasib in patients with KRAS G12C mutant NSCLC who have been exposed to prior G12C inhibitor and experienced progressive disease.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of VS-6766 in Combination With Adagrasib in Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer (NSCLC) (RAMP 204)
Actual Study Start Date : August 1, 2022
Estimated Primary Completion Date : July 24, 2024
Estimated Study Completion Date : January 1, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Avutometinib(VS-6766)+adagrasib
To determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients
Drug: Avutometinib (VS-6766) and adagrasib
The RP2D of VS-6766 + adagrasib determined in Part A will be used in Part B dose expansion
Other Name: KRAS G12C Inhibitor, adagrasib, MRTX849

Experimental: Avutometinib (VS-6766)+adagrasib RP2D
To determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients
Drug: Avutometinib (VS-6766) and adagrasib
The RP2D of VS-6766 + adagrasib determined in Part A will be used in Part B dose expansion
Other Name: KRAS G12C Inhibitor, adagrasib, MRTX849




Primary Outcome Measures :
  1. Part A: To determine RP2D for Avutometinib(VS-6766) in combination with adagrasib [ Time Frame: From start of treatment to confirmation of RP2D; 28 days ]
    Assessment of Dose-limiting toxicities (DLTs)

  2. To determine the efficacy of the optimal regimen identified from Part A [ Time Frame: From start of treatment to confirmation of response; 16 weeks ]
    Confirmed overall response rate per RECIST 1.1


Secondary Outcome Measures :
  1. To characterize the safety and toxicity profile: [ Time Frame: 24 Months ]
    • Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs) assessed by the toxicity grading of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0)
    • Severity of Adverse events (AEs) and Serious Adverse Events (SAEs) by toxicity grade assessed by the toxicity grading of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0)
    • Duration of Adverse events (AEs) and Serious Adverse Events (SAEs)
    • Incidence of clinically significant changes in lab parameters
    • Incidence of abnormal vital signs (including systolic and diastolic blood pressure in mmHg)

  2. ECG QT Interval [ Time Frame: 24 months ]
    Corrected ECG QT interval by Fredericia (QTcF)

  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 per RECIST 1.1

  4. Disease Control Rate (DCR) [ Time Frame: Greater than or equal to 8 weeks ]
    CR and PR stable disease as assessed per RECIST 1.1

  5. Progression Free Survival (PFS) [ Time Frame: 24 months ]
    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

  7. Plasma Pharmacokinetics (PK) of Avutometinib(VS 6766), adagrasib, and relevant metabolites - Tmax [ Time Frame: 10 weeks ]
    time of Maximum concentration (Tmax)

  8. Plasma Pharmacokinetics (PK) of Avutometinib(VS 6766), adagrasib, and relevant metabolites - AUC [ Time Frame: 10 weeks ]
    Area under plasma Concentration (AUC) 0 to t

  9. Plasma Pharmacokinetics (PK) of Avutometinib(VS 6766), adagrasib, and relevant metabolites - Half-life [ Time Frame: 10 weeks ]
    concentration Half-life (T1/2)

  10. Clinical Benefit Rate [ Time Frame: ≥ 6 months ]
    defined as Complete Response+Partial Response +Stable Disease



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 G12C mutation
  • The subject must have received prior therapy with a KRAS G12C inhibitor and experienced progression
  • Must have received appropriate treatment with at least one prior systemic regimen, but no more than 3 prior regimens, for Stage 3B-C or 4 NSCLC
  • 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:

  • Prior chemotherapy, targeted therapies, radiotherapy, immunotherapy or treatment with an investigational agent within 14 days of receipt of study drug (within 6 weeks for nitrosoureas, mitomycin C and chest radiation; within 6 months prior to Cycle 1 Day 1 for chest radiation > 30Gy)
  • History of prior malignancy, with the exception of curatively treated malignancies
  • Major surgery within 4 weeks (excluding placement of vascular access)
  • Exposure to strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy
  • Exposure to strong inhibitors of breast cancer resistance protein (BCRP) within 14 days prior to the first dose and during the course of therapy
  • Symptomatic brain metastases requiring steroids or other local interventions within the 2 weeks prior to initiation of therapy
  • Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
  • Known hepatitis B, hepatitis C, or human immunodeficiency virus infection that is active
  • Active skin disorder that has required systemic therapy within the past 1 year
  • History of rhabdomyolysis or interstitial lung disease
  • Concurrent ocular disorders
  • Concurrent heart disease or severe obstructive pulmonary disease
  • Subjects with the inability to swallow oral medications

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): NCT05375994


Contacts
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Contact: Gloria Patrick 1 781 292 4204 clinicaltrials@verastem.com
Contact: Matt Mockler 1 781 292 4204 clinicaltrials@verastem.com

Locations
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United States, California
UCSF Thoracic Oncology Not yet recruiting
San Francisco, California, United States, 94158
Contact: Bianca Bacaltos    415-885-3526    Bianca.Bacaltos@ucsf.edu   
Principal Investigator: Collin Blakely, MD         
United States, Colorado
University of Colorado Hospital Anschutz Cancer Pavllion Recruiting
Aurora, Colorado, United States, 80045
Contact: Halle Kuykendall    720-848-0356    halle.kuykendall@cuanschutz.edu   
Principal Investigator: David Camidge, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Principal Investigator: Kathryn Arbour, MD         
United States, Virginia
Virginia Cancer Specialists, NEXT Oncology Recruiting
Fairfax, Virginia, United States, 22031
Contact: MaryAnn Poole    703-280-5390    mpoole@nextoncology.com   
Principal Investigator: Alexander Spira, MD         
United States, Wisconsin
Medical College Wisconsin Not yet recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Val Hutsen    414-805-5856    vhutsen@mcw.edu   
Principal Investigator: Hui-Zi Chen, MD         
Sponsors and Collaborators
Verastem, Inc.
Mirati Therapeutics Inc.
Investigators
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Study Director: Hagop Youssoufian, MD Verastem, Inc.
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Responsible Party: Verastem, Inc.
ClinicalTrials.gov Identifier: NCT05375994    
Other Study ID Numbers: VS-6766-204
First Posted: May 17, 2022    Key Record Dates
Last Update Posted: November 28, 2022
Last Verified: November 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 G12C
Non Small Cell Lung Cancer
Metastatic Cancer
Adagrasib
Avutometinib(VS-6766)
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplastic Processes
Pathologic Processes
Adagrasib
Antineoplastic Agents