Defactinib, Avutometinib and Nivolumab for the Treatment of Anti-PD1 Refractory LKB1-Mutant Advanced Non-Small Cell Lung Cancer
NCT Number: NCT06495125
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Advanced Lung Adenocarcinoma|Refractory Lung Adenocarcinoma|Stage III Lung Cancer AJCC v8|Stage IV Lung Cancer AJCC v8
Interventions: DRUG: Avutometinib|PROCEDURE: Biopsy|PROCEDURE: Biospecimen Collection|PROCEDURE: Computed Tomography|DRUG: Defactinib|BIOLOGICAL: Nivolumab|PROCEDURE: Positron Emission Tomography
Sponsor: Emory University
Collaborators: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 50
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-31
Completion Date: 2026-06-30
Locations: Emory University Hospital Midtown, Atlanta, Georgia, 30308, United States|Emory University Hospital/Winship Cancer Institute, Atlanta, Georgia, 30322, United States|Emory Saint Joseph's Hospital, Atlanta, Georgia, 30342, United States

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.

Primary Outcome Measures: 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., At 6 months
Secondary Outcome Measures: 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., At start of treatment to progression or death up to 5 years|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., At start of treatment to death up to 5 years|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., At response to recurrent or progressive disease up to 5 years|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., Up to 30 days after last dose of study treatment