Clinical trial NCT05375994: Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: 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)
Lead sponsor: Verastem, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Mirati Therapeutics Inc.
First posted: 2022-05-17
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Part A: To determine RP2D for avutometinib(VS-6766) in combination with adagrasib
timeFrame: From start of treatment to confirmation of RP2D; 28 days
measure: To determine the efficacy of the optimal regimen identified from Part A
timeFrame: From start of treatment to confirmation of response; 16 weeks
Secondary outcomes:
measure: To characterize the safety and toxicity profile:
timeFrame: 24 Months
measure: ECG QT Interval
timeFrame: 24 months
measure: Duration of Response (DOR)
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: Greater than or equal to 8 weeks
measure: Progression Free Survival (PFS)
timeFrame: 24 months
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Tmax
timeFrame: 10 weeks
measure: Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - AUC
timeFrame: 10 weeks
measure: Plasma Pharmacokinetics (PK) of avutometinib(VS 6766), adagrasib, and relevant metabolites - Half-life
timeFrame: 10 weeks
measure: Clinical Benefit Rate
timeFrame: ≥ 6 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Thoracic Oncology
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital Anschutz Cancer Pavllion
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Cancer Center
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, NEXT Oncology
state: Virginia
city: Milwaukee
country: United States
facility: Medical College Wisconsin
state: Wisconsin
Study officials:
affiliation: Verastem, Inc.
name: MD Verastem
role: STUDY_DIRECTOR
References: