RAMP203: Phase 1/2 Study of VS-6766 + Sotorasib in G12C NSCLC Patients
Study Details
Study Description
Brief Summary
This study will assess the safety and efficacy of 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 |
|---|---|---|
|
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 VS-6766 in combination with sotorasib in patients with KRAS G12C mutant NSCLC.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: VS-6766+sotorasib To determine the recommended phase 2 dose (RP2D) for VS 6766 in combination with sotorasib in G12C inhibitor naïve and exposed patients |
Drug: VS-6766 and sotorasib
The RP2D of VS-6766 + sotorasib determined in Part A will be used in Part B dose expansion
Other Names:
|
| Experimental: VS-6766+sotorasib - G12C inhibitor naïve To determine the efficacy of the RP2D identified from Part A in G12C inhibitor naïve patients |
Drug: VS-6766 and sotorasib
The RP2D of VS-6766 + sotorasib determined in Part A will be used in Part B dose expansion
Other Names:
|
| Experimental: VS-6766+sotorasib - G12C inhibitor exposed To determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients |
Drug: VS-6766 and sotorasib
The RP2D of VS-6766 + sotorasib 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 sotorasib [From start of treatment to confirmation of RP2D; 28 days]
Assessment of Dose-limiting toxicities (DLTs)
- Part B: 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]
Treatment emergent adverse events/ treatment emergent serious adverse events - their frequency, duration and severity, lab parameters, vital signs and ECG changes based on CTCAE
- 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, sotorasib, and relevant metabolites - Tmax [10 weeks]
time of Maximum concentration (Tmax)
- Plasma Pharmacokinetics (PK) of VS 6766, sotorasib, and relevant metabolites -AUC [10 weeks]
Area under plasma Concentration (AUC) 0 to t
- Plasma Pharmacokinetics (PK) of VS 6766, sotorasib, and relevant metabolites half-life [10 weeks]
concentration Half-life (T1/2)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female patients ≥ 18 years of age
-
Histologic or cytologic evidence of NSCLC
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Known G12C KRAS mutation
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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
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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
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Measurable disease according to RECIST 1.1
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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:
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Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
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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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History of treatment with a direct and specific inhibitor of MEK
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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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Symptomatic brain metastases requiring steroids or other local interventions.
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Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
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Known hepatitis B, hepatitis C, or human immunodeficiency virus infection that is active
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Active skin disorder that has required systemic therapy within the past year
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History of rhabdomyolysis
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Concurrent ocular disorders
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Concurrent heart disease or severe obstructive pulmonary disease
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Inability to swallow oral medications
-
Female patients that are pregnant or breastfeeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 2 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 3 | Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care | Blacksburg | Virginia | United States | 24060 |
| 4 | Virginia Cancer Specialists, PC | Fairfax | Virginia | United States | 22031 |
Sponsors and Collaborators
- Verastem, Inc.
- Amgen
Investigators
- Study Director: Hagop Youssoufian, MD, Verastem Oncology
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VS-6766-203