Defactinib, Avutometinib and Nivolumab for the Treatment of 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, 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.