Clincosm LogoSign in Get a demo

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

Sponsor
Verastem, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05669482
Collaborator
(none)
40
Enrollment
1
Location
2
Arms
35.5
Anticipated Duration (Months)
1.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel
 Phase 1/Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Jan 15, 2023
Anticipated Primary Completion Date :
May 31, 2025
Anticipated Study Completion Date :
Dec 31, 2025

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel [28 days]

      Assessment of Dose-limiting toxicities (DLTs)

    2. To determine the efficacy of the RP2D identified in Part A [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])

    Secondary Outcome Measures

    1. Duration of Response (DOR) [24 months]

      Time of first response to PD as assessed per RECIST 1.1

    2. Disease Control Rate (DCR) [24 months]

      CR + PR + SD as assessed per RECIST 1.1

    3. Progression Free Survival (PFS) [24 months]

      From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause

    4. Overall Survival (OS) [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

    5. Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Tmax [10 weeks]

      Time to Maximum concentration (Tmax)

    6. Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, AUC [10 Weeks]

      Area under plasma Concentration (AUC) 0 to t

    7. Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Half-life [10 weeks]

      concentration Half-life (T1/2)

    8. Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs) [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

    9. Number of abnormal laboratory values [24 months]

      Count of abnormal laboratory values by grade

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University School of Medicine Saint Louis Missouri United States 63110

    Sponsors and Collaborators

    • Verastem, Inc.

    Investigators

    • Study Director: MD Verastem, Verastem, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Verastem, Inc.
    ClinicalTrials.gov Identifier:
    NCT05669482
    Other Study ID Numbers:
    • VS-6766-205
    First Posted:
    Dec 30, 2022
    Last Update Posted:
    Jan 4, 2023
    Last Verified:
    Jan 1, 2023
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Verastem, Inc.
    avutometinib (VS-6766)
    Metastatic Cancer
    KRAS Mutation
    Pancreatic Cancer
    Additional relevant MeSH terms:
    Neoplasms
    Neoplasm Metastasis
    Pancreatic Neoplasms
    Gemcitabine
    Paclitaxel

    Study Results

    No Results Posted as of Jan 4, 2023