Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer
- Conditions
- Metastatic CancerPancreas CancerNeoplasms PancreaticMalignant Neoplasm of PancreasKRAS Activating Mutation
- Interventions
- Registration Number
- NCT05669482
- Lead Sponsor
- Verastem, Inc.
- Brief Summary
This study will assess the safety and efficacy of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in patients with Pancreatic Ductal Adenocarcinoma (PDAC) who have been previously untreated.
- 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) and defactinib in combination with gemcitabine and nab-paclitaxel in patients previously untreated metastatic Pancreatic Ductal Adenocarcinoma (PDAC).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
- Male or female subjects ≥ 18 years of age
- Histologic or cytologic evidence of metastatic pancreatic ductal adenocarcinoma.
- An Eastern Cooperative Group (ECOG) performance status ≤ 1
- Measurable disease according to RECIST 1.1
- Adequate organ function
- Adequate cardiac function
- Agreement to use highly effective method of contraceptive
- Patients with pancreatic neuroendocrine tumors
- Prior or concomitant treatment for metastatic pancreatic ductal adenocarcinoma
- Prior treatment with inhibitors of the RAS /MAPK pathway [e.g. MEK inhibitors] or inhibitors of FAK
- History of prior malignancy, with the exception of curatively treated malignancies
- Major surgery within 4 weeks (excluding placement of vascular access)
- Concurrent heart disease or severe obstructive pulmonary disease
- Concurrent ocular disorders
- Active skin disorder that has required systemic therapy within the past 1 year
- Patients with interstitial lung disease or pulmonary fibrosis or severe lung disease, pulmonary edema, and adult respiratory distress syndrome
- Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2D avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel To determine the efficacy of the RP2D identified in Part A in untreated metastatic PDAC patients Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel To determine the recommended phase 2 dose (RP2D) for gemcitabine Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib in patients with untreated metastatic PDAC.
- Primary Outcome Measures
Name Time Method To determine the efficacy of the RP2D identified in Part A 6 months Confirmed overall response rate (ORR) (partial response \[PR\] + complete response \[CR\] defined according to Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\])
Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel 28 days Assessment of Dose-limiting toxicities (DLTs)
- Secondary Outcome Measures
Name Time Method Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Tmax 10 weeks Time to Maximum concentration (Tmax)
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, AUC 10 Weeks Area under plasma Concentration (AUC) 0 to t
Number of abnormal laboratory values 24 months Count of abnormal laboratory values by grade
Overall Survival (OS) Up to 5 years From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Half-life 10 weeks concentration Half-life (T1/2)
Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs) 24 months Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale
Disease Control Rate (DCR) 24 months CR + PR + SD as assessed per RECIST 1.1
Duration of Response (DOR) 24 months Time of first response to PD as assessed per RECIST 1.1
Progression Free Survival (PFS) 24 months From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause
Trial Locations
- Locations (12)
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
🇺🇸New York, New York, United States
New York Presbyterian/Weill-Cornell Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Utah Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States