Actively Recruiting
Defactinib, Avutometinib, and Nivolumab for Anti-PD1 Refractory LKB1-Mutant Advanced Lung Adenocarcinoma
Led by Emory University · Updated on 2026-04-06
50
Participants Needed
3
Research Sites
26 weeks
Total Duration
On this page
Sponsors
E
Emory University
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating how well a combination of defactinib, avutometinib, and nivolumab works in treating patients with LKB1-mutant non-small cell lung cancer that has not responded to prior anti-PD1 therapy. This phase II trial focuses on patients with advanced lung adenocarcinoma that may have spread locally or to distant parts of the body. The study aims to determine the progression-free survival at six months and also assess response rates, overall survival, and treatment side effects. Biomarker studies will be conducted using tumor samples from participants. Participants receive defactinib orally twice daily for 21 days, avutometinib orally twice weekly on specific days for 21 days, and nivolumab intravenously on day 1 of each 28-day cycle. Treatment cycles continue until disease progression or unacceptable side effects occur. During the study, patients undergo biopsies, blood sample collections, and imaging tests such as computed tomography (CT) or positron emission tomography (PET) to monitor the disease and treatment effects. After finishing study treatment, participants are followed up every three months for up to five years to monitor their health and disease status. Researchers will track progression-free survival, overall survival, duration of response, and adverse events throughout this period. The study involves regular assessments and monitoring to understand the impact of the drug combination on advanced lung adenocarcinoma.
CONDITIONS
Brief Title
Defactinib, Avutometinib and Nivolumab for the Treatment of Anti-PD1 Refractory LKB1-Mutant Advanced Non-Small Cell Lung Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Diagnosed with non-small cell lung cancer, specifically lung adenocarcinoma
- Have advanced stage disease not suitable for combined modality therapy or surgery
- Known LKB1 mutation
- For Cohort A: known KRAS mutation
- Progressed on prior immune checkpoint inhibitor therapy and first-line chemotherapy for advanced disease
- Measurable disease with at least one lesion meeting size criteria
- Age 18 years or older
- ECOG performance status 0 or 1
- Recovered from prior treatment toxicities to at least grade 1 (except alopecia and certain neuropathies)
- Adequate blood counts and organ function including neutrophils, hemoglobin, platelets, bilirubin, liver enzymes, and creatinine clearance
- Ability to take oral medications
- Agree to use adequate contraception if of child-bearing potential
- Able to understand and sign informed consent
- Baseline QTc interval within specified limits, excluding certain heart conduction abnormalities
You will not qualify if you...
- Received systemic therapy within 3 weeks before study or not recovered from earlier treatment adverse events
- Receiving other investigational agents
- Unstable or symptomatic brain metastases or leptomeningeal disease; stable asymptomatic brain metastases allowed under conditions
- History of autoimmune conditions posing high risk with nivolumab
- Serious autoimmune toxicity from prior immune checkpoint therapy
- Allergic reactions to similar drugs
- Uncontrolled illnesses including active infection, heart failure, unstable angina, arrhythmia, or psychiatric/social conditions limiting compliance
- Active hepatitis B, C, or HIV requiring therapy
- Active skin disorders needing systemic therapy within past year
- History of rhabdomyolysis
- Certain ocular disorders increasing risk for retinal vein occlusion or interfering with eye monitoring
- Inability to swallow oral meds or impaired gastrointestinal absorption
- Use of warfarin or drugs causing interactions with study drugs
- Known treatable driver mutations with approved therapies (except KRAS)
- Prior malignancy within 2 years except low-risk treated cancers
- Pregnant or breastfeeding women
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Repeated 28-day cycles until disease progression or unacceptable toxicity
Participants receive defactinib orally twice daily on days 1-21, avutometinib orally twice weekly on specific days for 21 days, and nivolumab intravenously on day 1 of each 28-day cycle. Treatment cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also undergo biopsy, blood sample collection, and CT or PET scans during the study.
Visits occur with each 28-day treatment cycle; biopsy, blood samples, and imaging are conducted during treatment
Duration - Up to 5 years
After completion of study treatment, participants are followed up every 3 months for up to 5 years to monitor overall survival and disease status.
Visits every 3 months
Trial Site Locations
Total: 3 locations
1
Emory University Hospital Midtown
Atlanta, Georgia, United States, 30308
Not Yet Recruiting
2
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Actively Recruiting
3
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States, 30342
Actively Recruiting
Research Team
C
Conor Steuer, MD
M
Mashunte Holmes, PhD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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