RAMP204: Study of VS-6766 + Adagrasib in KRAS G12C NSCLC Patients
Study Details
Study Description
Brief Summary
This study will assess the safety and efficacy of 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 |
|---|---|---|
|
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 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: VS-6766+adagrasib To determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients |
Drug: VS-6766 and adagrasib
The RP2D of VS-6766 + adagrasib determined in Part A will be used in Part B dose expansion
Other Names:
|
| Experimental: VS-6766+adagrasib RP2D To determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients |
Drug: VS-6766 and adagrasib
The RP2D of VS-6766 + adagrasib determined in Part A will be used in Part B dose expansion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Part A: To determine RP2D for VS-6766 in combination with adagrasib [From start of treatment to confirmation of RP2D; 28 days]
Assessment of Dose-limiting toxicities (DLTs)
- To determine the efficacy of the optimal regimen identified from Part A [From start of treatment to confirmation of response; 16 weeks]
Confirmed overall response rate per RECIST 1.1
Secondary Outcome Measures
- To characterize the safety and toxicity profile: [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)
- ECG QT Interval [24 months]
Corrected ECG QT interval by Fredericia (QTcF)
- 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 per RECIST 1.1
- Disease Control Rate (DCR) [Greater than or equal to 8 weeks]
CR and PR stable disease as assessed per RECIST 1.1
- Progression Free Survival (PFS) [24 months]
From the time of first dose of study intervention to PD or death from any cause
- Overall Survival (OS) [Up to 5 years]
From time of first dose of study intervention to death
- Plasma Pharmacokinetics (PK) of VS 6766, adagrasib, and relevant metabolites - Tmax [10 weeks]
time of Maximum concentration (Tmax)
- Plasma Pharmacokinetics (PK) of VS 6766, adagrasib, and relevant metabolites - AUC [10 weeks]
Area under plasma Concentration (AUC) 0 to t
- Plasma Pharmacokinetics (PK) of VS 6766, adagrasib, and relevant metabolites - Half-life [10 weeks]
concentration Half-life (T1/2)
- Clinical Benefit Rate [≥ 6 months]
defined as Complete Response+Partial Response +Stable Disease
Eligibility Criteria
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
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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)
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History of prior malignancy, with the exception of curatively treated malignancies
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Major surgery within 4 weeks (excluding placement of vascular access)
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Exposure to strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy
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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
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History of rhabdomyolysis or interstitial lung disease
-
Concurrent ocular disorders
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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 | University of Colorado Hospital Anschutz Cancer Pavllion | Aurora | Colorado | United States | 80045 |
| 2 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 3 | Virginia Cancer Specialists, NEXT Oncology | Fairfax | Virginia | United States | 22031 |
| 4 | Medical College Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Verastem, Inc.
- Mirati Therapeutics Inc.
Investigators
- Study Director: Hagop Youssoufian, MD, Verastem, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VS 6766-204