KRAS Activating MutationPhase 1/2RAMP205NCT05669482
Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer
A Phase 1/2 study testing avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in people with KRAS Activating Mutation and Metastatic Cancer, run by Verastem, Inc. at 12 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- KRAS Activating Mutation, Metastatic Cancer, Pancreas Cancer
- What is being tested?
- avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 12 sitesUnited States
- Study dates
- 22 Mar 2023to 31 Aug 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
University of Michigan Cancer Center
Ann Arbor, Michigan, 48109
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
University of Chicago
Chicago, Illinois, 60637
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
New York Presbyterian/Weill-Cornell Medical Center
New York, New York, 10021
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Utah Huntsman Cancer Institute
Salt Lake City, Utah, 84112
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
Virginia Mason Medical Center
Seattle, Washington, 98101
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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
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.
Read the 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).
- Conditions
- KRAS Activating Mutation, Metastatic Cancer, Pancreas Cancer, Neoplasms Pancreatic, Malignant Neoplasm of Pancreas
- Being tested
- avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel
- Keywords
- avutometinib (VS-6766), Metastatic Cancer, KRAS Mutation, Pancreatic Cancer
- Medical subject headings
- Neoplasm Metastasis, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxelDrug
Also called Gemzar, Abraxane
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.
| Study group | Role | What they receive |
|---|---|---|
| Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib | Experimental | To determine the recommended phase 2 dose (RP2D) for gemcitabine Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib in patients with untreated metastatic PDAC. Receives: Drug: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel |
| Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2D | Experimental | To determine the efficacy of the RP2D identified in Part A in untreated metastatic PDAC patients Receives: Drug: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel
Assessment of Dose-limiting toxicities (DLTs)
Measured: 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])
Measured: 6 months
Secondary outcomes (9)
Duration of Response (DOR)
Time of first response to PD as assessed per RECIST 1.1
Measured: 24 months
Disease Control Rate (DCR)
CR + PR + SD as assessed per RECIST 1.1
Measured: 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
Measured: 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
Measured: Up to 5 years
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Tmax
Time to Maximum concentration (Tmax)
Measured: 10 weeks
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, AUC
Area under plasma Concentration (AUC) 0 to t
Measured: 10 Weeks
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Half-life
concentration Half-life (T1/2)
Measured: 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
Measured: 24 months
Number of abnormal laboratory values
Count of abnormal laboratory values by grade
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2022
- Study start22 Mar 2023
- Primary completion31 Aug 2026 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for KRAS Activating MutationStudies of the same condition, open and under way.
- More trials run by Verastem, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Verastem, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD Verastem, Study director, Verastem, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05669482
- Sponsor's protocol ID
- VS-6766-205
- Acronym
- RAMP205
- Status last verified
- Aug 2025
- First submitted
- 6 Dec 2022
- Last updated
- 2 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05669482
- Acronym / sponsor ID
- RAMP205 / VS-6766-205
- Conditions
- KRAS Activating Mutation, Metastatic Cancer, Pancreas Cancer, Neoplasms Pancreatic, Malignant Neoplasm of Pancreas
- Keywords
- avutometinib (VS-6766), Metastatic Cancer, KRAS Mutation, Pancreatic Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Verastem, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Mar 2023 (actual)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 30 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib | Experimental | Drug: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxelTo determine the recommended phase 2 dose (RP2D) for gemcitabine Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib in patients with untreated metastatic PDAC. |
| Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2D | Experimental | Drug: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxelTo determine the efficacy of the RP2D identified in Part A in untreated metastatic PDAC patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxelAlso: Gemzar, AbraxaneThe 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. | Drug | Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib, Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2D |
Primary outcome
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)
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])
9 secondary outcomes
Duration of Response (DOR)
Time frame: 24 months
Disease Control Rate (DCR)
Time frame: 24 months
Progression Free Survival (PFS)
Time frame: 24 months
Overall Survival (OS)
Time frame: Up to 5 years
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Tmax
Time frame: 10 weeks
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, AUC
Time frame: 10 Weeks
Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Half-life
Time frame: 10 weeks
Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)
Time frame: 24 months
Number of abnormal laboratory values
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD Verastem study director
Verastem, Inc.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in people with KRAS Activating Mutation and Metastatic Cancer, run by Verastem, Inc. at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2025.