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Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients (RAMP204)

Primary Purpose

Non Small Cell Lung Cancer, KRAS Activating Mutation, Advanced Cancer

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

avutometinib (VS-6766) and adagrasib

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring NSCLC, KRAS G12C, Non Small Cell Lung Cancer, Metastatic Cancer, Adagrasib, Avutometinib (VS-6766)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

UCSF Thoracic OncologyRecruiting
University of Colorado Hospital Anschutz Cancer PavllionRecruiting
Mayo Clinic Cancer CenterRecruiting
Mayo Clinic Cancer CenterRecruiting
Memorial Sloan Kettering Cancer CenterRecruiting
University of North Carolina at Chapel HillRecruiting
Virginia Cancer Specialists, NEXT OncologyRecruiting
Medical College WisconsinRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

avutometinib(VS-6766)+adagrasib

avutometinib (VS-6766)+adagrasib RP2D

Arm Description

To determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients

To determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients

Outcomes

Primary Outcome Measures

Part A: To determine RP2D for avutometinib(VS-6766) in combination with adagrasib

Assessment of Dose-limiting toxicities (DLTs)

To determine the efficacy of the optimal regimen identified from Part A

Confirmed overall response rate per RECIST 1.1

Secondary Outcome Measures

To characterize the safety and toxicity profile:

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)

ECG QT Interval

Corrected ECG QT interval by Fredericia (QTcF)

Duration of Response (DOR)

Time of first response to PD as assessed per RECIST 1.1

Disease Control Rate (DCR)

CR and PR stable disease as assessed per RECIST 1.1

Progression Free Survival (PFS)

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

Overall Survival (OS)

From time of first dose of study intervention to death

Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Tmax

time of Maximum concentration (Tmax)

Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - AUC

Area under plasma Concentration (AUC) 0 to t

Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Half-life

concentration Half-life (T1/2)

Clinical Benefit Rate

defined as Complete Response+Partial Response +Stable Disease

Full Information

NCT ID

NCT05375994

First Posted

May 2, 2022

Last Updated

July 19, 2023

Sponsor

Verastem, Inc.

Collaborators

Mirati Therapeutics Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05375994

Brief Title

Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients

Acronym

RAMP204

Official Title

A Phase 1/2 Study of Avutometinib (VS-6766) in Combination With Adagrasib in Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer (NSCLC) (RAMP 204)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 1, 2022 (Actual)

Primary Completion Date

July 24, 2024 (Anticipated)

Study Completion Date

January 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Verastem, Inc.

Collaborators

Mirati Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non Small Cell Lung Cancer, KRAS Activating Mutation, Advanced Cancer, Metastatic Cancer, Malignant Neoplasm of Lung, Malignant Neoplastic Disease

Keywords

NSCLC, KRAS G12C, Non Small Cell Lung Cancer, Metastatic Cancer, Adagrasib, Avutometinib (VS-6766)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

85 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

avutometinib(VS-6766)+adagrasib

Arm Type

Experimental

Arm Description

To determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients

Arm Title

avutometinib (VS-6766)+adagrasib RP2D

Arm Type

Experimental

Arm Description

To determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients

Intervention Type

Drug

Intervention Name(s)

avutometinib (VS-6766) and adagrasib

Other Intervention Name(s)

KRAS G12C Inhibitor, adagrasib, KRAZATI®

Intervention Description

The RP2D of VS-6766 + adagrasib determined in Part A will be used in Part B dose expansion

Primary Outcome Measure Information:

Title

Part A: To determine RP2D for avutometinib(VS-6766) in combination with adagrasib

Description

Assessment of Dose-limiting toxicities (DLTs)

Time Frame

From start of treatment to confirmation of RP2D; 28 days

Title

To determine the efficacy of the optimal regimen identified from Part A

Description

Confirmed overall response rate per RECIST 1.1

Time Frame

From start of treatment to confirmation of response; 16 weeks

Secondary Outcome Measure Information:

Title

To characterize the safety and toxicity profile:

Description

Time Frame

24 Months

Title

ECG QT Interval

Description

Corrected ECG QT interval by Fredericia (QTcF)

Time Frame

24 months

Title

Duration of Response (DOR)

Description

Time of first response to PD as assessed per RECIST 1.1

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

Title

Disease Control Rate (DCR)

Description

CR and PR stable disease as assessed per RECIST 1.1

Time Frame

Greater than or equal to 8 weeks

Title

Progression Free Survival (PFS)

Description

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

Time Frame

24 months

Title

Overall Survival (OS)

Description

From time of first dose of study intervention to death

Time Frame

Up to 5 years

Title

Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Tmax

Description

time of Maximum concentration (Tmax)

Time Frame

10 weeks

Title

Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - AUC

Description

Area under plasma Concentration (AUC) 0 to t

Time Frame

10 weeks

Title

Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Half-life

Description

concentration Half-life (T1/2)

Time Frame

10 weeks

Title

Clinical Benefit Rate

Description

defined as Complete Response+Partial Response +Stable Disease

Time Frame

≥ 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Verastem Call Center

Phone

1 781 292 4204

clinicaltrials@verastem.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

MD Verastem

Organizational Affiliation

Verastem, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

UCSF Thoracic Oncology

City

San Francisco

State/Province

California

ZIP/Postal Code

94158

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bianca Bacaltos

Phone

415-885-3526

Bianca.Bacaltos@ucsf.edu

First Name & Middle Initial & Last Name & Degree

Collin Blakely, MD

Facility Name

University of Colorado Hospital Anschutz Cancer Pavllion

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Halle Kuykendall

Phone

720-848-0356

halle.kuykendall@cuanschutz.edu

First Name & Middle Initial & Last Name & Degree

David Camidge, MD

Facility Name

Mayo Clinic Cancer Center

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32224

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yanyan Lou

Phone

855-776-0015

lou.yanyan@mayo.edu

First Name & Middle Initial & Last Name & Degree

YanYan Lou, MD

Facility Name

Mayo Clinic Cancer Center

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kaushal Parikh

Phone

855-776-0015

parikh.kaushal@mayo.edu

First Name & Middle Initial & Last Name & Degree

Kaushal Parikh, MD

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kathryn Arbour, MD

Facility Name

University of North Carolina at Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

275514

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bryana Roberts

Phone

919-966-4432

bryana_roberts@med.unc.edu

First Name & Middle Initial & Last Name & Degree

Jared Weiss, MD

Facility Name

Virginia Cancer Specialists, NEXT Oncology

City

Fairfax

State/Province

Virginia

ZIP/Postal Code

22031

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

MaryAnn Poole

Phone

703-280-5390

mpoole@nextoncology.com

First Name & Middle Initial & Last Name & Degree

Alexander Spira, MD

Facility Name

Medical College Wisconsin

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nicholas Pucek

Phone

414-805-3158

npucek@mcw.edu

First Name & Middle Initial & Last Name & Degree

Hui-Zi Chen, MD

12. IPD Sharing Statement

Learn more about this trial

Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients

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