Clinical trial NCT05669482: Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: KRAS Activating Mutation
Metastatic Cancer
Pancreas Cancer
Neoplasms Pancreatic
Malignant Neoplasm of Pancreas
Keywords: avutometinib (VS-6766)
Metastatic Cancer
KRAS Mutation
Pancreatic Cancer
Lead sponsor: Verastem, Inc.
Sponsor class: INDUSTRY
First posted: 2022-12-30
Enrollment: 40
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) 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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel
timeFrame: 28 days
measure: To determine the efficacy of the RP2D identified in Part A
timeFrame: 6 months
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: 24 months
measure: Disease Control Rate (DCR)
timeFrame: 24 months
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) and Defactinib and relevant metabolites, Tmax
timeFrame: 10 weeks
measure: Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, AUC
timeFrame: 10 Weeks
measure: Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Half-life
timeFrame: 10 weeks
measure: Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 24 months
measure: Number of abnormal laboratory values
timeFrame: 24 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: New York
country: United States
facility: New York Presbyterian/Weill-Cornell Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
affiliation: Verastem, Inc.
name: MD Verastem
role: STUDY_DIRECTOR
References: