Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer (RAMP205)

March 4, 2024 updated by: Verastem, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2
  • Phase 1

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

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Helen Diller Family Comprehensive Cancer Center
        • Principal Investigator:
          • Andrew Ko, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago
        • Contact:
        • Principal Investigator:
          • Shergill Ardaman, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Dana Farber Cancer Institute
        • Principal Investigator:
          • Kimberly Perez, MD
        • Contact:
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Principal Investigator:
          • Kian-Huat Lim, MD
        • Contact:
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Principal Investigator:
          • Anna Varghese, MD
      • New York, New York, United States, 10016
        • Recruiting
        • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
        • Contact:
        • Principal Investigator:
          • Kristen Spencer, DO
      • New York, New York, United States, 10021
        • Recruiting
        • New York Presbyterian/Weill-Cornell Medical Center
        • Contact:
        • Principal Investigator:
          • Despina Siolas, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania
        • Principal Investigator:
          • Mark O'Hara, MD
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • University of Utah Huntsman Cancer Institute
        • Principal Investigator:
          • Ignacio Garrido-Laguna
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98101
        • Recruiting
        • Virginia Mason Medical Center
        • Principal Investigator:
          • Vincent Picozzi, MD
        • Contact:
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center
        • Contact:
        • Principal Investigator:
          • Rachael Safyan, MD

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

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.
Other Names:
  • Gemzar
  • Abraxane
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.
Other Names:
  • Gemzar
  • Abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel
Time Frame: 28 days
Assessment of Dose-limiting toxicities (DLTs)
28 days
To determine the efficacy of the RP2D identified in Part A
Time Frame: 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])
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR)
Time Frame: 24 months
Time of first response to PD as assessed per RECIST 1.1
24 months
Disease Control Rate (DCR)
Time Frame: 24 months
CR + PR + SD as assessed per RECIST 1.1
24 months
Progression Free Survival (PFS)
Time Frame: 24 months
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)
Time Frame: 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
Up to 5 years
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Tmax
Time Frame: 10 weeks
Time to Maximum concentration (Tmax)
10 weeks
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, AUC
Time Frame: 10 Weeks
Area under plasma Concentration (AUC) 0 to t
10 Weeks
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Half-life
Time Frame: 10 weeks
concentration Half-life (T1/2)
10 weeks
Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)
Time Frame: 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
24 months
Number of abnormal laboratory values
Time Frame: 24 months
Count of abnormal laboratory values by grade
24 months

Collaborators and Investigators

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

Sponsor

Verastem, Inc.

Investigators

  • Study Director: MD Verastem, Verastem, Inc.

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 Major Dates

Study Start (Actual)

March 22, 2023

Primary Completion (Estimated)

May 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

December 6, 2022

First Submitted That Met QC Criteria

December 19, 2022

First Posted (Actual)

December 30, 2022

Study Record Updates

Last Update Posted (Estimated)

March 5, 2024

Last Update Submitted That Met QC Criteria

March 4, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VS-6766-205

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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