A Phase 2 Study of Defactinib and Avutometinib, in Combination With Nivolumab for Patients With Anti-PD1 Refractory LKB1-Mutant Advanced Lung Adenocarcinoma
Emory University
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 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.
Description
PRIMARY OBJECTIVE: I. 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: I. To evaluate response rate, overall survival and toxicity assessment. TERTIARY/EXPLORATORY OBJECTIVE: I. 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, T…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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 t…
Interventions
- DrugAvutometinib
Given PO
- ProcedureBiopsy
Undergo biopsy
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureComputed Tomography
Undergo CT
- DrugDefactinib
Given PO
- BiologicalNivolumab
Given IV
- ProcedurePositron Emission Tomography
Undergo PET
Locations (3)
- Emory University Hospital MidtownAtlanta, Georgia
- Emory University Hospital/Winship Cancer InstituteAtlanta, Georgia
- Emory Saint Joseph's HospitalAtlanta, Georgia