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Non Small Cell Lung CancerPhase 2RAMP202NCT04620330

A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer

A Phase 2 study testing avutometinib (VS-6766) and avutometinib (VS-6766) and Defactinib in people with Non Small Cell Lung Cancer and KRAS Activating Mutation, run by Verastem, Inc. at 45 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy or VS-6766 in combination with defactinib in subjects with recurrent Non-small cell lung cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
avutometinib (VS-6766) and avutometinib (VS-6766) and Defactinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
45 sitesin 5 countries
Study dates
31 Dec 2020to 12 Dec 2023
Phase
Phase 2
Are there results?
None posted in the registry

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 NSCLC
  • Known KRAS or BRAF mutation
  • The subject must have received appropriate prior therapy
  • Measurable disease according to RECIST 1.1
  • An Eastern Cooperative Group (ECOG) performance status ≤ 1
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  • Adequate organ function
  • Adequate recovery from toxicities related to prior treatments
  • Agreement to use highly effective method of contraceptive

Who cannot join

  • Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
  • History of prior malignancy, with the exception of curatively treated malignancies
  • Major surgery within 4 weeks (excluding placement of vascular access)
  • History of treatment with a direct and specific inhibitor of MEK, KRAS or BRAF except for treatment of BRAF V-600E mutant NSCLC
  • Exposure to strong CYP2C9 and CYP3A4 inhibitors or inducers within 7 days prior to the first dose and during the course of therapy
  • Symptomatic brain metastases requiring steroids or other local interventions.
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  • Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
  • Active skin disorder that has required systemic therapy within the past 1 year
  • History of rhabdomyolysis
  • Concurrent ocular disorders
  • Concurrent heart disease or severe obstructive pulmonary disease
  • Subjects with the inability to swallow oral medications

Trial locations and contacts

45 sites in 5 countries.

45 sites in 5 countries

United States28 sites

  • Emory University School of Medicine

    Atlanta, Georgia, 30322

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Hematology/Oncology Clinic, LLP

    Baton Rouge, Louisiana, 70809

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Chattanooga Oncology Hematology Assoc.

    Chattanooga, Tennessee, 037404

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Medical Center-Duchossois Center for Advanced Medicine

    Chicago, Illinois, 60637

  • Maryland Oncology Hematology P.A

    Columbia, Maryland, 21044

  • Zangmeister Cancer Center

    Columbus, Ohio, 43219

  • Texas Oncology

    Dallas, Texas, 75246

  • Henry Ford Cancer Institute/Henry Ford Health System

    Detroit, Michigan, 48202

  • City of Hope

    Duarte, California, 91010

  • Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

  • Florida Cancer Specialists

    Fort Myers, Florida, 33908

  • Texas Oncology Ft Worth Cancer Center

    Fort Worth, Texas, 76104

  • Texas Oncology

    Grapevine, Texas, 76051

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Northwell Health-Monter Cancer Center

    Lake Success, New York, 11042

  • Rocky Mountain Cancer Centers

    Lone Tree, Colorado, 80124

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Illinois Cancer Specialists

    Niles, Illinois, 60714

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Univ. of Pittsburgh Med Center

    Pittsburgh, Pennsylvania, 15232

  • Northwest Cancer Specialists, P.C.

    Portland, Oregon, 97213

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Florida Cancer Specialists

    St. Petersburg, Florida, 33705

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

France5 sites

  • Centre Leon Berard

    Lyon, 69373

  • Hopital Nord Marseille

    Marseille, 13915

  • Hopital Cochin

    Paris, 75014

  • Institute De Cancerologie De L'Ouest Site Paul Papin Oncologie Medicale

    Saint-Herblain, 44805

  • Cancerologie Gustave Roussy - Cancer Medicine

    Villejuif, 94800

Other trials in France

Spain5 sites

  • Complejo Hospitalario Universiario a Coruna Teresa

    A Coruña, 15006

  • Hospital Clinic de Barcelona

    Barcelona

  • Hospital 12 de Octubre

    Córdoba, 28041

  • Universitario de Teatinos

    Málaga, 29010

  • Hospital Universitario Virgen de la Macarena

    Seville, 41009

Other trials in Spain

Italy4 sites

  • Irccs, Irts

    Meldola, 47014

  • Azienda Ospedaliera Universitaria

    Orbassano, Torino, 10043

  • UOC di Oncologia Medica

    Parma, 43126

  • Centro Ricerche Cliniche di Verona

    Verona, 37134

Other trials in Italy

Germany3 sites

  • Klinikum Chemnitz gGmbH

    Chemnitz, 09116

  • Universitatsklinkum Leipzig

    Leipzig, 04103

  • Evangelisches Klinkum Bethel

    Straße, 33611

Other trials in Germany

About this study

Official title: A Phase 2 Study of Avutometinib (VS-6766) (Dual RAF/MEK Inhibitor) as a Single Agent and In Combination With Defactinib (FAK Inhibitor) in Recurrent KRAS-Mutant (KRAS-MT) and BRAF-Mutant (BRAF-MT) Non-Small Cell Lung Cancer (NSCLC) (RAMP 202)

This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy or VS-6766 in combination with defactinib in subjects with recurrent Non-small cell lung cancer.

Read the detailed description

This is a multicenter, open-label Phase 2 study designed to evaluate safety and tolerability and efficacy of avutometinib (VS-6766) versus avutometinib (VS-6766) in combination with defactinib in subjects with KRAS and BRAF mutant NSCLC following treatment with an appropriate platinum-based regimen and an approved immune checkpoint inhibitor (CPI).

Being tested
avutometinib (VS-6766), avutometinib (VS-6766) and Defactinib
Keywords
NSCLC, KRAS-G12V, G12V, BRAF, V600E, KRAS
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • avutometinib (VS-6766)Drug

    Monotherapy

  • avutometinib (VS-6766) and DefactinibDrug

    Also called avutometinib (VS-6766) and VS-6063

    Combination therapy

Study groups in NCT04620330
Study groupRoleWhat they receive
Arm 1: avutometinib (VS-6766) monotherapyExperimentalin patients with NSCLC KRAS-G12V tumor
Receives: Drug: avutometinib (VS-6766)
Arm 2: avutometinib (VS-6766) in combination with defactinibExperimentalin patients with a NSCLC KRAS-G12V tumor
Receives: Drug: avutometinib (VS-6766) and Defactinib
Arm 3: avutometinib (VS-6766) in combination with defactinibExperimentalin patients with a NSCLC KRAS-other (non-G12V) tumor
Receives: Drug: avutometinib (VS-6766) and Defactinib
Arm 4: avutometinib (VS-6766) in combination with defactinibExperimentalin patients with a NSCLC BRAF-V600E tumor
Receives: Drug: avutometinib (VS-6766) and Defactinib
Arm 5:avutometinib (VS-6766) in combination with defactinibExperimentalin patients with a NSCLC BRAF-non-V600E tumor
Receives: Drug: avutometinib (VS-6766) and Defactinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC

    Confirmed overall response rate per RECIST 1.1

    Measured: From start of treatment to confirmation of response; 24 weeks

  2. To evaluate the initial efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC

    Confirmed overall response rate per RECIST 1.1

    Measured: From start of treatment to confirmation of response; 24 weeks

  3. To determine efficacy in KRAS-other (non-G12V) NSCLC

    Confirmed overall response rate per RECIST 1.1

    Measured: From start of treatment to confirmation of response; 24 weeks

  4. To determine the efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC

    Confirmed overall response rate per RECIST 1.1

    Measured: From start of treatment to confirmation of response; 24 weeks

Secondary outcomes (6)

  1. To characterize the safety and toxicity profile of VS-6766 as a monotherapy and in combination with defactinib in KRAS-MT NSCLC and in BRAF-MT NSCLC

    Adverse events (AEs), serious AEs (SAEs), vital signs, physical examinations, clinical laboratory values, and tolerability (dose interruptions/reductions)

    Measured: 24 weeks

  2. Overall Response Rate per RECIST 1.1 as assessed by Investigator

    Proportioned subjects achieving a CR or PR as assess by the investigator

    Measured: From start of treatment to confirmation of response; 24 weeks

  3. Duration of Response (DOR)

    Time of first response to PD as assessed by the IRC

    Measured: Time from the first documentation of response to first documentation of progressive disease or death due to any cause, greater than or equal to 6 months

  4. Disease Control Rate (DCR)

    CR and PR stable disease as assessed by the IRC

    Measured: Greater than or equal to 8 weeks

  5. Progression Free Survival (PFS)

    From the time of first dose of study intervention to PD or death from any cause

    Measured: Up to 5 years

  6. Overall Survival (OS)

    From time of first dose of study intervention to death

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2020
  2. Study start31 Dec 2020
  3. Primary completion29 Aug 2023
  4. Study completion12 Dec 2023

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04620330
Sponsor's protocol ID
VS-6766-202
Acronym
RAMP202
Status last verified
Jan 2024
First submitted
5 Nov 2020
Last updated
12 Jan 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Capelletto E, Bironzo P, Denis L, Koustenis A, Bungaro M, Novello S. Single agent VS-6766 or VS-6766 plus defactinib in KRAS-mutant non-small-cell lung cancer: the RAMP-202 phase II trial. Future Oncol. 2022 May;18(16):1907-1915. doi: 10.2217/fon-2021-1582. Epub 2022 Mar 14.

    PubMed 35285277

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing avutometinib (VS-6766) and avutometinib (VS-6766) and Defactinib in people with Non Small Cell Lung Cancer and KRAS Activating Mutation, run by Verastem, Inc. at 45 sites in 5 countries.

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 9 inclusion and 12 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: finished, as of the sponsor's last update on 12 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in United States, France, Spain, Italy, Germany. 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 phase mean?

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC (time frame: From start of treatment to confirmation of response; 24 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04620330, which also lists 1 linked publication.

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 12 Jan 2024.

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