PhI/II Study of Amivantamab and Tepotinib Combo in MET-altered Non-small Cell Lung Cancer

Primary Objectives: 1. For the safety run-in portion of the trial: 2. To evaluate dose-limiting toxicity (DLT) and to establish the recommended phase II dose (RP2D) of amivantmab given in combination with tepotinib in patients with advanced MET-altered NSCLC. The primary endpoint is dose-limiting toxicity (DLT) and recommended phase 2 dose (RP2D). 3. For the efficacy portion of the trial: 4. To preliminarily assess efficacy of amivantamab + tepotinib combination in cohort A (MET exon 14 skipping TKI-naïve) , in terms of objective response rate. Secondary Objectives 1. Determine whether amivantamab + tepotinib improves objective response rate in each cohort (cohort B and cohort C) 2. Determine whether amivantamab + tepotinib improves disease control rate (DCR) in each cohort 3. Determine whether amivantamab + tepotinib improves Duration of Response (DoR) in each cohort 4. Determine the safety and tolerability of amivantamab + tepotinib in each cohort Exploratory Objectives 1. Explore the association of baseline genomic profiles (from tumor, germline DNA, and ctDNA) with clinical benefit in patients treated with amivantamab + tepotinib 2. Explore resistance mechanisms to amivantamab + tepotinib combination. At the time of progression, patients will undergo ctDNA genomic tests and a biopsy (optional). The purpose of this additional tissue acquisition is for molecular analysis and comparison with the initial specimen, to determine if there are changes in molecular alterations or pathways that shed light on mechanisms of resistance. 3. Determine the immunomodulatory effects of amivantamab + tepotinib combination.