NCT06495125

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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, 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.

Conditions

• Advanced Lung Adenocarcinoma
• Refractory Lung Adenocarcinoma
• Stage III Lung Cancer AJCC v8
• Stage IV Lung Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Avutometinib	Given PO
PROCEDURE	Biopsy	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Defactinib	Given PO
BIOLOGICAL	Nivolumab	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET

Timeline

• Start date: 2024-07-31
• Primary completion: 2029-03-17
• Completion: 2029-09-17
• First posted: 2024-07-10
• Last updated: 2026-04-06

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study