Telisotuzumab Vedotin and Osimertinib for the Treatment of Progressive, Incurable, Non Small Cell Lung Cancer
brief summary
This phase II trial tests how well telisotuzumab vedotin and osimertinib works for the treatment of non small cell lung cancer that is growing, spreading, or getting worse (progressive) and for which no treatment is currently available (incurable). Telisotuzumab vedotin is a monoclonal antibody, called telisotuzumab, linked to a toxic agent, called vedotin. Telisotuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as c-Met receptors, and delivers vedotin to kill them. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving telisotuzumab vedotin and osimertinib may be effective for treating progressive, incurable non small cell lung cancer.
detailed description
PRIMARY OBJECTIVES:
I. Objective response rate (ORR) as defined as complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
II. Progression free survival (PFS) as defined by time from treatment initiation to disease progression per RECIST 1.1 criteria or death.
SECONDARY OBJECTIVES:
I. Duration of response (DOR), time to response (TTR) and overall survival (OS).
II. Assess the safety and tolerability of induction and maintenance schedule of telisotuzumab vedotin when given with osimertinib in all evaluable patients who received at least one dose of study regimen.
EXPLORATORY OBJECTIVES:
I. Assess potential biomarkers associated with response from liquid biopsies and archival or fresh tissue biopsy.
Ia. Correlate tissue biomarkers such as MET expression level by immunohistochemistry and ribonucleic acid (RNA) expression with response; Ib. Where an archival specimen is available from prior to treatment with an EGFR tyrosine kinase inhibitor (TKI) and can be compared to a more recent specimen, the dynamics and predictive value of c-MET overexpression will be evaluated.
II. Assess participant-reported outcomes on quality of life using Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) questionnaire.
OUTLINE:
Patients receive telisotuzumab vedotin intravenously (IV) on days 1 and 15 of cycles 1-3 and on day 1 of subsequent cycles. Patients also receive osimertinib orally (PO) daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, brain magnetic resonance imaging (MRI), if needed, and blood sample collection throughout the study. Patients also optionally undergo tumor biopsy during follow-up.
After completion of study treatment, patients are followed up at 30 days and every 6 weeks or 12 weeks for up to 2 years.
official title
A Phase II Trial of Telisotuzumab Vedotin With Osimertinib for EGFR Mutated NSCLC With c-MET Overexpression That is Progressing on Osimertinib