Summary

This phase II Expanded Lung-MAP treatment trial tests tepotinib with or without ramucirumab for the treatment of patients with advanced non-small cell lung cancer that has spread from where it first started (primary site) to other places in the body (stage IV) or that has come back after a period of improvement (recurrent). Tepotinib is used in patients whose cancer has a mutated (changed) form of a gene called MET. It is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal MET protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving tepotinib with ramucirumab may lower the chance of the cancer from growing or spreading in patients with stage IV or recurrent non-small cell lung cancer.

Objectives

PRIMARY OBJECTIVE:
I. To compare the response rate (confirmed or unconfirmed, complete or partial) between participants with MET exon 14 skipping positive non-small cell lung cancer (NSCLC) randomized to tepotinib with or without ramucirumab.

SECONDARY OBJECTIVES:
I. To compare the frequency of all-grade treatment- related peripheral edema as defined by Common Terminology Criteria for Adverse Events (CTCAE) between the arms.
II. To evaluate the frequency and severity of toxicities within each arm.
III. To compare progression-free survival between the arms.
IV. To compare overall survival between the arms.
V. To estimate the duration of response (DoR) among responders within each arm.

TRANSLATIONAL MEDICINE OBJECTIVE:
I. To establish a tissue/blood repository for participants with MET exon 14 skipping non-small cell lung cancer (NSCLC).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive ramucirumab intravenously (IV) over 30-60 minutes on day 1 of each cycle and tepotinib orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive tepotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients undergo lymphoscintigraphy scan at screening prior to treatment, at the first occurrence of peripheral edema (defined as the development of grade = 1 CTCAE Edema Limbs affecting either the arms, hands, or legs), and if peripheral edema increases in attribution. Patients also undergo computed tomography (CT) scan and/or magnetic resonance imaging (MRI) throughout the trial. Patients also undergo blood sample collection while on study.

After completion of study treatment, patients are followed-up every 12 weeks or more often as clinically indicated until progression and then every 6 months for 2 years and at the end of 3 years from date of sub-study randomization.