Study Of Avutometinib (VS-6766) +Defactinib With Gemcitabine And Nab-paclitaxel In Patients With Pancreatic Cancer

Study Overview

Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer

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.

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).

KRAS Activating Mutation
Metastatic Cancer
Pancreas Cancer
Neoplasms Pancreatic
Malignant Neoplasm of Pancreas

DRUG: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel

VS-6766-205

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-12-06	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-06-20
First Submitted that Met QC Criteria 2022-12-19	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-06-24
First Posted (ACTUAL) 2022-12-30	Results First Posted N/A	Last Verified 2025-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib To determine the recommended phase 2 dose (RP2D) for gemcitabine Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib in patients with untreated metastatic PDAC.	DRUG: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel 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.
EXPERIMENTAL: Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2D To determine the efficacy of the RP2D identified in Part A in untreated metastatic PDAC patients	DRUG: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel 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.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib

To determine the recommended phase 2 dose (RP2D) for gemcitabine Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib in patients with untreated metastatic PDAC.

DRUG: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel

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.

EXPERIMENTAL: Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2D

To determine the efficacy of the RP2D identified in Part A in untreated metastatic PDAC patients

DRUG: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel

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.

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Duration of Response (DOR)	Time of first response to PD as assessed per RECIST 1.1	24 months
Disease Control Rate (DCR)	CR + PR + SD as assessed per RECIST 1.1	24 months
Progression Free Survival (PFS)	From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause	24 months
Overall Survival (OS)	From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause	Up to 5 years
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Tmax	Time to Maximum concentration (Tmax)	10 weeks
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, AUC	Area under plasma Concentration (AUC) 0 to t	10 Weeks
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Half-life	concentration Half-life (T1/2)	10 weeks
Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)	Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale	24 months
Number of abnormal laboratory values	Count of abnormal laboratory values by grade	24 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Verastem Call Center

Phone Number: 1 781 292 4204

Email: clinicaltrials@verastem.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: MD Verastem, Verastem, Inc.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record