Actively Recruiting
Defactinib, Avutometinib and Nivolumab for the Treatment of Anti-PD1 Refractory LKB1-Mutant Advanced Non-Small Cell Lung Cancer
Led by Emory University · Updated on 2026-04-06
50
Participants Needed
3
Research Sites
267 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
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.
CONDITIONS
Official 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...
- Histological or cytological diagnosis of non-small cell lung cancer, specifically lung adenocarcinoma
- Advanced stage disease not suitable for combined therapy or surgery
- Known LKB1 mutation
- For Cohort A: known KRAS mutation
- Progression after immune checkpoint inhibitor therapy and first-line chemotherapy for advanced disease
- Measurable disease with at least one lesion meeting size requirements
- Age 18 years or older
- ECOG performance status of 0 or 1
- Recovery from prior treatment toxicities to at least grade 1, except alopecia and peripheral neuropathy grade 2 or less
- Absolute neutrophil count 1500/mcL or higher
- Hemoglobin 8.0 or higher
- Platelets 100,000/mcL or higher
- Total bilirubin 1.5 times upper limit of normal or less (higher allowed for Gilbert syndrome)
- AST and ALT 2.5 times upper limit of normal or less (or less than 5 times with liver metastases)
- Creatinine clearance 60 mL/min/1.73 m2 or higher if creatinine elevated
- Ability to take oral medications
- Agreement to use contraception during and after study participation if of child-bearing potential
- Ability and willingness to provide informed consent
- Baseline corrected QT interval less than 460 ms for women and 450 ms for men (unless bundle branch block)
You will not qualify if you...
- Systemic therapy within 3 weeks before study or unresolved adverse effects from therapy given more than 4 weeks prior
- Use of other investigational agents
- Unstable or symptomatic brain metastasis or leptomeningeal disease; stable asymptomatic brain metastases allowed under conditions
- History of autoimmune conditions increasing risk with nivolumab
- Prior serious autoimmune toxicity from immune checkpoint inhibitors
- Allergic reactions to drugs similar to avutometinib or defactinib
- Uncontrolled illness including infection, heart failure, unstable angina, arrhythmia, or psychiatric/social issues affecting compliance
- Active hepatitis B, hepatitis C, or HIV infection requiring therapy
- Active skin disorders needing systemic therapy within past year, except treated early skin cancers or topical treatments
- History of rhabdomyolysis
- Certain eye disorders including glaucoma, retinal vein occlusion risks, or significant corneal disease
- Inability to swallow oral medications or impaired gastrointestinal absorption
- Treatment with warfarin or interacting drugs within 14 days before the first dose and during therapy
- Known treatable driver mutations with FDA-approved therapies except KRAS
- Prior malignancy within 2 years except cured or low-risk cancers
- Pregnancy or breastfeeding in female patients
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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
CONTACT
M
Mashunte Holmes, PhD
CONTACT
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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