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

Metastatic Cancer Clinical Trial

— RAMP205  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05669482
• Other study ID #: VS-6766-205
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 22, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: Verastem, Inc.
• Contact: Verastem Call Center
• Phone: 1 781 292 4204
• Email: clinicaltrials[@]verastem.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York Presbyterian/Weill-Cornell Medical Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah Huntsman Cancer Institute	Salt Lake City	Utah
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Verastem, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Duration of Response (DOR)	Time of first response to PD as assessed per RECIST 1.1	24 months
Secondary	Disease Control Rate (DCR)	CR + PR + SD as assessed per RECIST 1.1	24 months
Secondary	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
Secondary	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
Secondary	Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Tmax	Time to Maximum concentration (Tmax)	10 weeks
Secondary	Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, AUC	Area under plasma Concentration (AUC) 0 to t	10 Weeks
Secondary	Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Half-life	concentration Half-life (T1/2)	10 weeks
Secondary	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
Secondary	Number of abnormal laboratory values	Count of abnormal laboratory values by grade	24 months