AzTrials
AzTrials

Advanced Lung AdenocarcinomaPhase 2NCT06495125

Defactinib, Avutometinib and Nivolumab for the Treatment of Anti-PD1 Refractory LKB1-Mutant Advanced Non-Small Cell Lung Cancer

A Phase 2 study testing Avutometinib, Biopsy and Biospecimen Collection in people with Advanced Lung Adenocarcinoma and Refractory Lung Adenocarcinoma, run by Emory University at 3 sites 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
Search all trials

Trial summary

This phase II trial tests how well defactinib and avutometinib in combination with nivolumab works in treating patients with LKB1-mutant non-small cell lung cancer that has not responded (refractory) to an anti-PD1 treatment and may have spread from where it first started to nearby tissue, lymph nodes, or distant… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Avutometinib, Biopsy and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
3 sitesUnited States
Study dates
31 Jul 2024to 17 Sep 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

  • Patients must have been histologically or cytologically diagnosed with non-small cell lung cancer, specifically lung adenocarcinoma
  • Patients must have advanced stage disease that is not amenable to combined modality therapy or surgical resection
  • Patients must have known LKB1 mutation
  • COHORT A ONLY: Patients must have known KRAS mutation
  • Patients must have progressed on prior therapy with immune checkpoint inhibitor alone and first line chemotherapy, either combined or sequentially, for advanced stage disease. No other lines of chemotherapy in the advanced stage therapy is allowed. The exception is patients with KRAS G12C are also allowed the use of one line of targeted Food and Drug Administration (FDA) approved therapy
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
Show all 19Show fewer
  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate recovery from toxicities related to prior treatments to at least grade 1 by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Exceptions include alopecia and peripheral neuropathy grade ≤ 2
  • Absolute neutrophil count ≥ 1,500/mcL
  • Hemoglobin ≥ 8.0
  • Platelets ≥ 100,000/mcL
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution; patients with Gilbert syndrome may enroll if total bilirubin < 3.0 mg/dL (51 umole/L)
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (or < 5 x ULN in patients with liver metastases)
  • Creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Patients must have the ability to ingest oral medications
  • The effects of defactinib and avutometinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry,for the duration of study participation, for 3 months following the last dose of study therapy for male patients, and 1 month following the last dose of study therapy for female patients. 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
  • Patients must be able to understand and be willing to sign a written informed consent document
  • Baseline corrected QT (QTc) interval < 460 ms for women and ≤ 450 ms for men (average of triplicate readings) (CTCAE grade 1) using Fredericia's QT correction formula. NOTE: This criterion does not apply to patients with a right or left bundle branch block

Who cannot join

  • Patients who have had systemic therapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are receiving any other investigational agents
  • Patients with unstable or symptomatic brain metastasis or known leptomeningeal disease. Asymptomatic brain metastases are allowed if they meet the following criteria:
  • Have been treated and have been stable for greater than or equal to 4 weeks as documented by radiologic imaging
  • Have not required increasing doses of corticosteroids within 2 weeks prior to study treatment
  • Patients with history of pre-existing auto-immune conditions that would pose a higher risk for toxicity with nivolumab will be excluded
Show all 22Show fewer
  • Patients who experienced serious auto-immune toxicity with prior immune checkpoint inhibitor therapy
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to avutometinib or defactinib
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Known hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection that is active and/or requires therapy
  • Active skin disorder that has required systemic therapy within the past 1 year. Surgically removed early stage skin cancers are allowed. Topical creams are allowed as well
  • History of rhabdomyolysis
  • Concurrent ocular disorders:
  • 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
  • Patients with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease
  • Treatment with warfarin. Patients on warfarin for deep vein thrombosis/pulmonary embolism should be converted to low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs). Exposure to medications (with or without prescriptions), supplements, herbal remedies, or foods with potential for drug-drug interactions with defactinib within 14 days prior to the first dose of avutometinib or defactinib 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
  • Patients with a known "treatable driver mutation" with FDA approved targeted therapy (such as EGFR, ALK, ROS1, NTRK, BRAF, RET, MET exon 14, HER2). The exception is KRAS as listed in the inclusion section
  • History of prior malignancy within past 2 years prior to study entry, with the exception of curatively treated malignancies or malignancies with very low potential for recurrence or progression
  • Female patients who are pregnant or breastfeeding

Trial locations and contacts

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

Conor Steuer, MD contact

404-778-5378

csteuer@emory.edu

Mashunte Holmes, PhD contact

404-754-4990

mashunte.holmes@emory.edu

United States3 sites, 3 recruiting

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

    Conor Steuer, MD, csteuer@emory.edu

    Not yet recruiting

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

    Conor E. Steuer, 404-778-5378, csteuer@emory.edu

    Conor E. Steuer

    Recruiting

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

    Conor Steuer, MD, csteuer@emory.edu

    Recruiting

Other trials in United States

About this study

Official title: A Phase 2 Study of Defactinib and Avutometinib, in Combination With Nivolumab for Patients With Anti-PD1 Refractory LKB1-Mutant Advanced Lung Adenocarcinoma

This phase II trial tests how well defactinib and avutometinib in combination with nivolumab works in treating patients with LKB1-mutant non-small cell lung cancer that has not responded (refractory) to an anti-PD1 treatment and may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Defactinib and avutometinib belong to a class of drugs called kinase inhibitors. These drugs target kinase proteins found in tumor cells. Tumor cells need these proteins to survive and grow. By blocking these proteins, defactinib and avutometinib may cause tumors to stop growing or grow more slowly. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. Giving defactinib and avutometinib in combination with nivolumab may kill more tumor cells in patients with anti-PD1 refractory LKB1-mutant advanced non-small cell lung cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the efficacy (6-months progression free survival [PFS] rate) of defactinib and avutometinib when combined with nivolumab in patients with LKB1 mutated lung adenocarcinoma.

SECONDARY OBJECTIVE:

  1. To evaluate response rate, overall survival and toxicity assessment.

TERTIARY/EXPLORATORY OBJECTIVE:

  1. Biomarker evaluation will be conducted on archived tumor samples and on-study biopsies obtained in a subset of patients.

OUTLINE:

Patients receive defactinib orally (PO) twice daily (BID) on days 1-21, avutometinib PO twice weekly on Monday and Thursday, Tuesday and Friday or Wednesday and Saturday for 21 days and nivolumab intravenously (IV) on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy, blood sample collection, computed tomography (CT) or positron emission tomography (PET) on study.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Being tested
Avutometinib, Biopsy, Biospecimen Collection, Computed Tomography, Defactinib
Medical subject headings
Adenocarcinoma of Lung, Lung Neoplasms

What participants receive

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

  • AvutometinibDrug

    Also called CH-5126766, CH5126766, CKI-27, R-7304

    Given PO

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • DefactinibDrug

    Also called PF-04554878, VS-6063

    Given PO

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS-936558, CMAB819

    Given IV

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET

Study groups in NCT06495125
Study groupRoleWhat they receive
Treatment (defactinib, avutometinib, nivolumab)ExperimentalPatients receive defactinib PO BID on days 1-21, avutometinib PO twice weekly on Monday and Thursday, Tuesday and Friday or Wednesday and Saturday for 21 days and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy, blood sample collection, CT or PET on study.
Receives: Drug: Avutometinib; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Defactinib; Biological: Nivolumab; Procedure: Positron Emission Tomography

What is being measured

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

  1. Progression free survival (PFS)

    PFS will be defined as the time from the date of first protocol therapy to the date of first documentation of disease progression or death due to any cause, whichever occurs first. PFS will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. PFS will be calculated with a 95% confidence interval using Kaplan-Meier method based on the efficacy evaluable population.

    Measured: At 6 months

Secondary outcomes (4)

  1. PFS

    PFS will be defined as the time from the date of first protocol therapy to the date of first documentation of disease progression or death due to any cause, whichever occurs first. PFS will be evaluated using RECIST v1.1. The Kaplan-Meier method will be used to estimate the median PFS with 95% confidence interval.

    Measured: At start of treatment to progression or death up to 5 years

  2. Overall survival (OS)

    OS will be measured from the date of first protocol treatment to the date of death. The Kaplan-Meier method will be used to estimate OS with 95% confidence interval.

    Measured: At start of treatment to death up to 5 years

  3. Duration of response (DOR)

    DOR will be measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is documented. Summary statistics will be used to describe the mean and median DOR.

    Measured: At response to recurrent or progressive disease up to 5 years

  4. Incidence of adverse events (AEs)

    AEs will be graded using National Cancer Institute Common Toxicity Criteria for Adverse Events v5.0. All AEs will be summarized and described within each cohort. The incidence of severe events or toxicities will be described as well as the proportion of patients with grade 3 or higher toxicity.

    Measured: Up to 30 days after last dose of study treatment

Timeline

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

  1. First posted10 Jul 2024
  2. Study start31 Jul 2024
  3. Primary completion17 Mar 2029 (estimated)
  4. Study completion17 Sep 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
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06495125
Sponsor's protocol ID
STUDY00006144
Other IDs
NCI-2024-04302, STUDY00006144, WINSHIP5947-23, P01CA257906, P30CA138292
Status last verified
Mar 2026
First submitted
2 Jul 2024
Last updated
6 Apr 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, Biopsy and Biospecimen Collection in people with Advanced Lung Adenocarcinoma and Refractory Lung Adenocarcinoma, run by Emory University at 3 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 19 inclusion and 22 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 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 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 Conor Steuer, MD (404-778-5378, csteuer@emory.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) (time frame: At 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 NCT06495125.

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 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in