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Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib in G12C NSCLC Patients (RAMP203)

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ClinicalTrials.gov Identifier: NCT05074810
Recruitment Status : Recruiting
First Posted : October 12, 2021
Last Update Posted : March 15, 2023
Sponsor:
Collaborator:
Amgen
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) in combination with sotorasib in patients with G12C Non-Small Cell Lung Cancer (NSCLC) in patients who have been exposed to prior G12C inhibitor and those who have not been exposed to prior G12C inhibitor.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer KRAS Activating Mutation Drug: avutometinib (VS-6766) and sotorasib Phase 1 Phase 2

Detailed Description:
This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety and tolerability and efficacy of avutometinib (VS-6766) in combination with sotorasib in patients with KRAS G12C mutant NSCLC.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Avutometinib (VS-6766) in Combination With Sotorasib in Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer (NSCLC)
Actual Study Start Date : April 12, 2022
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : September 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Sotorasib

Arms and Interventions
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Arm Intervention/treatment
Experimental: avutometinib (VS-6766)+sotorasib
To determine the recommended phase 2 dose (RP2D) for avutometinib (VS 6766) in combination with sotorasib in G12C inhibitor naïve and exposed patients
 Drug: avutometinib (VS-6766) and sotorasib
The RP2D of avutometinib(VS-6766) + sotorasib determined in Part A will be used in Part B dose expansion
Other Names:
  • AMG 510
  • LUMAKRAS™
Experimental: avutometinib (VS-6766)+sotorasib - G12C inhibitor naïve
To determine the efficacy of the RP2D identified from Part A in G12C inhibitor naïve patients
 Drug: avutometinib (VS-6766) and sotorasib
The RP2D of avutometinib(VS-6766) + sotorasib determined in Part A will be used in Part B dose expansion
Other Names:
  • AMG 510
  • LUMAKRAS™
Experimental: avutometinib (VS-6766)+sotorasib - G12C inhibitor exposed
To determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients
 Drug: avutometinib (VS-6766) and sotorasib
The RP2D of avutometinib(VS-6766) + sotorasib determined in Part A will be used in Part B dose expansion
Other Names:
  • AMG 510
  • LUMAKRAS™


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

  2. Part B: 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 ]
    Treatment emergent adverse events/ treatment emergent serious adverse events - their frequency, duration and severity, lab parameters, vital signs and ECG changes based on CTCAE

  2. 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

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

  4. Progression Free Survival (PFS) [ Time Frame: 24 months ]
    From the time of first dose of study intervention to PD or death from any cause

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

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

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

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


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 patients ≥ 18 years of age
  • Histologic or cytologic evidence of NSCLC
  • Known G12C KRAS mutation
  • Have not received a KRAS inhibitor to be included in Part A and Part B, Cohort 1
  • Received at least 1 dose of a G12C inhibitor to be included in Part A or Part B Cohort 2
  • 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:

  • 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
  • Exposure to strong CYP3A4 inhibitors or inducers within 14 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
  • Known hepatitis B, hepatitis C, or human immunodeficiency virus infection that is active
  • 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
  • Inability to swallow oral medications
  • Female patients that are pregnant or breastfeeding
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): NCT05074810


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

Locations
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United States, District of Columbia
Georgetown University Medical Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Jeannette Crawford    202-687-0893    jeanette.g.crawford@medstar.net   
Principal Investigator: Joshua Reuss, MD         
United States, Illinois
Illinois Cancer Specialists Recruiting
Arlington Heights, Illinois, United States, 60005
Contact: Laura Lozano    847-463-2604    Laura.Lozano@usoncology.com   
Principal Investigator: Rajat Malhotra, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Dana Farber Cancer Institute    877-338-7425      
Principal Investigator: Mark Awad, MD         
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Contact: Marybeth McCarthy    313-725-7855    mmccart2@hfhs.org   
Principal Investigator: Shirish Gadgeel, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Tara Ryan    314-273-0144    rtara@wustl.edu   
Principal Investigator: Ramaswamy Govindan, MD         
United States, Texas
Texas Oncology Recruiting
Austin, Texas, United States, 78731
Contact: Amy Ressel    512-427-9400    amy.ressel@usoncology.com   
Principal Investigator: Jeffrey Yorio, MD         
United States, Virginia
Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care Recruiting
Blacksburg, Virginia, United States, 24060
Contact: Natasha Holt    540-808-1704    mailto:Natasha.Holt@USONCOLOGY.COM   
Principal Investigator: Jerome Goldschmidt         
Virginia Cancer Specialists, PC Recruiting
Fairfax, Virginia, United States, 22031
Contact: Carrie Friedman    703-636-1473    mailto:carrie.friedman@usoncology.com   
Principal Investigator: Alexander Spira, MD         
Sponsors and Collaborators
Verastem, Inc.
Amgen
Investigators
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Study Director: MD Verastem Verastem, Inc.
More Information
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Responsible Party: Verastem, Inc.
ClinicalTrials.gov Identifier: NCT05074810    
Other Study ID Numbers: VS-6766-203
First Posted: October 12, 2021    Key Record Dates
Last Update Posted: March 15, 2023
Last Verified: March 2023

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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
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