Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer
RAMP205
A Phase 1b/2a Study of Gemcitabine and Nab-paclitaxel in Combination With Avutometinib (VS-6766) and Defactinib in Patients With Previously Untreated Metastatic Adenocarcinoma of the Pancreas
1 other identifier
interventional
40
1 country
12
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Mar 2023
Longer than P75 for phase_1
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 6, 2022
CompletedFirst Posted
Study publicly available on registry
December 30, 2022
CompletedStudy Start
First participant enrolled
March 22, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2027
September 2, 2025
August 1, 2025
3.4 years
December 6, 2022
August 29, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel
Assessment of Dose-limiting toxicities (DLTs)
28 days
To determine the efficacy of the RP2D identified in Part A
Confirmed overall response rate (ORR) (partial response \[PR\] + complete response \[CR\] defined according to Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\])
6 months
Secondary Outcomes (9)
Duration of Response (DOR)
24 months
Disease Control Rate (DCR)
24 months
Progression Free Survival (PFS)
24 months
Overall Survival (OS)
Up to 5 years
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Tmax
10 weeks
- +4 more secondary outcomes
Study Arms (2)
Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib
EXPERIMENTALTo determine the recommended phase 2 dose (RP2D) for gemcitabine Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib in patients with untreated metastatic PDAC.
Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2D
EXPERIMENTALTo determine the efficacy of the RP2D identified in Part A in untreated metastatic PDAC patients
Interventions
The RP2D of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel determined in Part A will be used in Part B dose expansion.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Verastem, Inc.lead
Study Sites (12)
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158, United States
University of Chicago
Chicago, Illinois, 60637, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016, United States
New York Presbyterian/Weill-Cornell Medical Center
New York, New York, 10021, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Utah Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
Virginia Mason Medical Center
Seattle, Washington, 98101, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
MD Verastem
Verastem, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 6, 2022
First Posted
December 30, 2022
Study Start
March 22, 2023
Primary Completion (Estimated)
August 31, 2026
Study Completion (Estimated)
August 31, 2027
Last Updated
September 2, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will not share