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Gastric CancerPhase 2NCT06487221

Avutometinib and Defactinib in Diffuse Gastric Cancer

A Phase 2 study testing Avutometinib and Defactinib in people with Gastric Cancer and Stomach Cancer, run by Ryan H. Moy, MD, PhD at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The purpose of this study is to determine if the combination study treatment with avutometinib and defactinib will prolong life in participants, is effective in decreasing the size of the tumor(s), and if it is safe in subjects with diffuse-type stomach cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gastric Cancer, Stomach Cancer
What is being tested?
Avutometinib and Defactinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
28 Oct 2024to 30 May 2029
Phase
Phase 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

  • Histologic or cytologic evidence of gastric/gastroesophageal junction carcinoma, classified as diffuse type, poorly cohesive, signet ring cell, or mixed type. Patients with known pathogenic CDH1 and/or RHOA mutations will be allowed regardless of histology.
  • Prior therapy with at least one line of therapy for unresectable/metastatic disease, which must include platinum and fluoropyrimidine.
  • ECOG performance status of 0 or 1
  • Age ≥ 18 years
  • Adequate organ function, defined by the following laboratory parameters:
  • Adequate hematologic function, including hemoglobin [Hb] ≥ 9.0 g/dL; platelets ≥ 100,000/mm3; and absolute neutrophil count [ANC] ≥ 1500/mm3. If a red blood cell transfusion or erythropoiesis-stimulating agent has been administered the Hb must remain stable and ≥ 9 g/dL for at least 1 week prior to first dose of study intervention.
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  • Subjects with Hgb ≥ 8.5 g/dL and <9.0 g/dL are eligible if there is no history of significant cardiovascular risk features as per the investigator (i.e., prior myocardial infarction) b. Adequate hepatic function: (i) total bilirubin ≤ 1.5 × upper limit of normal [ULN] for the institution; patients with Gilbert syndrome may enroll if total bilirubin is < 3.0 mg/dL (51 μmol/L); (ii) alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
  • ≤ 2.5 × ULN (or < 5 x ULN in patients with liver metastases). c. Adequate renal function with creatinine clearance rate of ≥ 50 mL/min, as calculated by the Cockcroft-Gault formula d. International normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x ULN in the absence of anticoagulation or therapeutic levels in the presence of anticoagulation.
  • Albumin ≥ 3.0 g/dL (451 μmol/L). f. Creatine phosphokinase (CPK) ≤ 2.5 x ULN. g. Adequate cardiac function with left ventricular ejection fraction ≥ 55% by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan.
  • Disease that can be evaluated radiographically, which can be measurable disease or non-measurable disease per RECIST 1.1. All radiology studies must be performed within 28 days prior to start of study-directed therapy.
  • Tumor that is amenable to fresh biopsy, which may include malignant ascites that is amenable for paracentesis.
  • Baseline QTc interval < 460 ms for females and ≤ 450 ms for males (average of triplicate readings) using Fredericia's QT correction formula. NOTE: This criterion does not apply to subjects with a right or left bundle branch block.
  • Adequate recovery from toxicities related to prior treatments to at least Grade 1 by CTCAE v 5.0. Exceptions include alopecia and peripheral neuropathy grade ≤ 2. Subjects with other toxicities that are stable on supportive therapy may be allowed to participate with prior approval from the principal investigator.
  • The effects of the study drugs on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (see Section 7.6 for Contraception Guidance) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after the last dose of the study drug.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Systemic anti-cancer therapy within 3 weeks of the first dose of study therapy, or within 5 half-lives of the previous drug, whichever is shorter.
  • Patients currently receiving any other investigational agent.
  • Subjects may not have had a history of malignancy other that esophagogastric cancer within two years prior to screening, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year overall survival >90%) such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer.
  • Major surgery within 4 weeks or palliative radiotherapy within 1 week of the first dose of study therapy.
  • Treatment with warfarin. Subjects on warfarin for DVT/PE can be converted to low- molecular-weight heparin (LMWH).
  • History of treatment with a direct and specific inhibitor of FAK, MEK, or KRAS.
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  • Patients who had exposure to medications (with or without prescriptions), supplements, herbal remedies, or foods with potential for drug-drug interactions with avutometinib and/or defactinib within 14 days prior to the first dose of study intervention and during the course of therapy, including:
  • Strong CYP3A4 inhibitors or inducers.
  • Strong CYP2C9 inhibitors or inducers.
  • Strong P-glycoprotein (P-gp) inhibitors or inducers
  • Strong breast cancer resistance protein (BCRP) inhibitors or inducers
  • Symptomatic brain metastases requiring steroids or other local interventions. Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks prior to first dose of study therapy, and are neurologically stable.
  • Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection that is active and/or requires therapy. HIV patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the investigational agents.
  • Active skin disorder that has required systemic therapy within the past 1 year.
  • History of rhabdomyolysis.
  • Concurrent ocular disorders including the following:
  • Patients with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes.
  • Patients with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure > 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO.
  • Patients with active or chronic, visually significant corneal disorders, other active ocular conditions requiring ongoing therapy or clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy. Examples of visually significant corneal disorders include corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions. Visually significant corneal disorders do NOT include dry eyes, blepharitis, and uncomplicated corneal erosions.
  • Concurrent congestive heart failure, prior history of class III/IV cardiac disease (New York Heart Association [NYHA]), myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina or severe obstructive pulmonary disease.
  • Inability to swallow oral medications.
  • History of hypersensitivity to any of the inactive ingredients (hydroxylpropylmethylcellulose, mannitol, magnesium stearate) of the investigational product.
  • Female subjects who are pregnant or breastfeeding. Pregnant women are excluded from this study because the risk for teratogenic or abortifacient effects with the investigational agents is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with the investigational agents.
  • Any other medical condition (e.g., cardiac, gastrointestinal, pulmonary, psychiatric, neurological, genetic, etc.) that in the opinion of the investigator would place the subject at unacceptably high risk for toxicity.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Research Nurse Navigator contact

212-342-5162

cancerclinicaltrials@cumc.columbia.edu

United States1 site, 1 recruiting

  • Columbia University Irving Medical Center

    New York, New York, 10032

    Research Nurse Navigator, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu

    Ryan Moy, MD, PhD

    Recruiting

Other trials in United States

About this study

Official title: A Phase II Trial of Avutometinib in Combination With Defactinib in Metastatic Diffuse Gastric Cancer

The purpose of this study is to determine if the combination study treatment with avutometinib and defactinib will prolong life in participants, is effective in decreasing the size of the tumor(s), and if it is safe in subjects with diffuse-type stomach cancer.

Read the detailed description

There are two main types of stomach cancer based on the appearance under the microscope: intestinal-type and diffuse-type. Some stomach cancers also have a mix of intestinal-type and diffuse-type (mixed type). The participants are being invited to take part in this research study due to having been diagnosed with stomach cancer that has spread to other parts of the body and/or cannot be surgically removed, has diffuse-type or mixed type cells or has gene changes that are associated with diffuse-type stomach cancers (such as mutations in the genes called CDH1 or RHOA), and have already been treated with chemotherapy and the disease is now growing. Defactinib is an oral drug that inhibits the protein focal adhesion kinase (FAK), which has been shown to promote growth of gastric cancer. Avutometinib (also known as VS-6766) is an oral drug that blocks an important signaling pathway in cancer cells known as the MAP kinase pathway. Avutometinib inhibits two proteins in the MAPK kinase pathway, RAF and MEK. The purpose of this study is to determine if the combination study treatment with defactinib and avutometinib is effective in improving the length of time after the start of treatment in which a participant is alive and their cancer does not grow or spread.

Being tested
Avutometinib, Defactinib
Medical subject headings
Stomach Neoplasms

What participants receive

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

  • AvutometinibDrug

    Also called VS6766

    3.2mg orally

  • DefactinibDrug

    Also called VS-6063

    200 mg orally

Study groups in NCT06487221
Study groupRoleWhat they receive
Avutometinib & DefactinibExperimentalAvutometinib: Study participants will receive Avutometinib 3.2mg orally two times per week for three weeks in a row followed by one week of rest Defactinib: Study participants will receive Defactinib 200mg twice daily for three weeks in a row followed by one week of rest
Receives: Drug: Avutometinib; Drug: Defactinib

What is being measured

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

  1. Progression-free survival (PFS) Rate

    To determine the efficacy of combination defactinib and avutometinib in patients with metastatic diffuse gastric cancer (DGC) as measured by 6-month progression-free survival (PFS) rate. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

    Measured: 6 months

Secondary outcomes (5)

  1. Overall Response Rate (ORR)

    Overall response rate (ORR) defined as partial response (PR) + complete response (CR) according to Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR is a disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

    Measured: 6 months

  2. Median Progression-Free Survival

    To determine the impact of combination defactinib and avutometinib on other measures of efficacy off progression free survival (PFS). Time from the start of treatment until disease progression or death, whichever comes first.

    Measured: 24 months

  3. Median Overall Survival (OS)

    Overall survival defined as the time from the start of treatment until death or last follow-up.

    Measured: Up to 5 years

  4. Disease Control Rate (DCR)

    DCR defined as Complete Response (CR)+ Progressive Disease (PD)+ Stable Disease (SD) as assessed per RECISIT 1. CR is a disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

    Measured: 24 months

  5. Duration of response (DOR)

    The duration of overall response is measured from the time measurement criteria are met for CR (Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm) or PR (At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters), whichever is first recorded, until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: 24 months

Timeline

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

  1. First posted5 Jul 2024
  2. Study start28 Oct 2024
  3. Primary completion30 Nov 2028 (estimated)
  4. Study completion30 May 2029 (estimated)

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06487221
Sponsor's protocol ID
AAAV0009
Status last verified
Nov 2026
First submitted
26 Jun 2024
Last updated
6 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avutometinib and Defactinib in people with Gastric Cancer and Stomach Cancer, run by Ryan H. Moy, MD, PhD at 1 site 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 15 inclusion and 24 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: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 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?

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?

Contact Research Nurse Navigator (212-342-5162, cancerclinicaltrials@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) Rate (time frame: 6 months). 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 NCT06487221.

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 6 Nov 2026.

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