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

Primary Purpose

KRAS Activating Mutation, Metastatic Cancer, Pancreas Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel
Sponsored by
Verastem, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for KRAS Activating Mutation focused on measuring avutometinib (VS-6766), Metastatic Cancer, KRAS Mutation, Pancreatic Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dana Farber Cancer InstituteRecruiting
  • Washington University School of MedicineRecruiting
  • Laura & Isaac Perlmutter Cancer Center at NYU Langone HealthRecruiting
  • New York Presbyterian/Weill-Cornell Medical CenterRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • University of PennsylvaniaRecruiting
  • Virginia Mason Medical CenterRecruiting
  • Fred Hutchinson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

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

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

Arm Description

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

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

Outcomes

Primary Outcome Measures

Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel
Assessment of Dose-limiting toxicities (DLTs)
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])

Secondary Outcome Measures

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

Full Information

First Posted
December 6, 2022
Last Updated
October 24, 2023
Sponsor
Verastem, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05669482
Brief Title
Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 22, 2023 (Actual)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Verastem, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
KRAS Activating Mutation, Metastatic Cancer, Pancreas Cancer, Neoplasms Pancreatic, Malignant Neoplasm of Pancreas
Keywords
avutometinib (VS-6766), Metastatic Cancer, KRAS Mutation, Pancreatic Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib
Arm Type
Experimental
Arm Description
To determine the recommended phase 2 dose (RP2D) for gemcitabine Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib in patients with untreated metastatic PDAC.
Arm Title
Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2D
Arm Type
Experimental
Arm Description
To determine the efficacy of the RP2D identified in Part A in untreated metastatic PDAC patients
Intervention Type
Drug
Intervention Name(s)
avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel
Other Intervention Name(s)
Gemzar, Abraxane
Intervention Description
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 Measure Information:
Title
Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel
Description
Assessment of Dose-limiting toxicities (DLTs)
Time Frame
28 days
Title
To determine the efficacy of the RP2D identified in Part A
Description
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])
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
Time of first response to PD as assessed per RECIST 1.1
Time Frame
24 months
Title
Disease Control Rate (DCR)
Description
CR + PR + SD as assessed per RECIST 1.1
Time Frame
24 months
Title
Progression Free Survival (PFS)
Description
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause
Time Frame
24 months
Title
Overall Survival (OS)
Description
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause
Time Frame
Up to 5 years
Title
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Tmax
Description
Time to Maximum concentration (Tmax)
Time Frame
10 weeks
Title
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, AUC
Description
Area under plasma Concentration (AUC) 0 to t
Time Frame
10 Weeks
Title
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Half-life
Description
concentration Half-life (T1/2)
Time Frame
10 weeks
Title
Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)
Description
Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale
Time Frame
24 months
Title
Number of abnormal laboratory values
Description
Count of abnormal laboratory values by grade
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Verastem Call Center
Phone
1 781 292 4204
Email
clinicaltrials@verastem.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD Verastem
Organizational Affiliation
Verastem, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kimberly Perez
Phone
617-632-6491
Email
Kimberly_Perez@DFCI.HARVARD.EDU
First Name & Middle Initial & Last Name & Degree
Kimberly Perez, MD
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lynne Mitchell
Phone
314-273-6758
Email
lynne.mitchell@wustl.edu
First Name & Middle Initial & Last Name & Degree
Kian-Huat Lim, MD
Facility Name
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristen Spencer
Phone
212-731-6000
Email
Kristen.Spencer@nyulangone.org
First Name & Middle Initial & Last Name & Degree
Kristen Spencer, DO
Facility Name
New York Presbyterian/Weill-Cornell Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Casey Owens
Email
cdo4001@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Despina Siolas, MD
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Varghese, MD
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luda Mazaleuskya
Phone
267-455-9141
Email
mazali@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
Mark O'Hara, MD
Facility Name
Virginia Mason Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Colleen Soleau
Phone
206-287-6272
Email
Colleen.Soleau@vmfh.org
First Name & Middle Initial & Last Name & Degree
Vincent Picozzi, MD
Facility Name
Fred Hutchinson Cancer Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rachael Safyan
Phone
206-606-2038
Email
rsafyan2@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Rachael Safyan, MD

12. IPD Sharing Statement

Learn more about this trial

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

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