Mass General - Division of Clinical Research

Part 1: - Histologically or cytologically confirmed locally advanced, recurrent or metastatic NSCLC and have received available standard of care therapy. - There is no limit on the number of prior therapies that can have been received. Part 2: Cohort A: - Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic non-squamous NSCLC. - Tumor sample with high cMET expression by IHC confirmed by central laboratory testing. Cohort B: - Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic non-squamous NSCLC. - Tumor sample with intermediate cMET expression by IHC confirmed by central laboratory testing. Cohort C: - Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic squamous NSCLC. - Tumor sample with cMET overexpression by IHC confirmed by central laboratory testing. Cohort D: - Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic NSCLC. - Tumor sample that does not meet cMET IHC entry criteria for Cohorts A-C - Known MET amplification or exon 14 skipping mutations respectively. Patients with MET exon 14 skipping mutations must have received MET TKI therapy if available and considered standard of care. Cohort E: - Have histologically or cytologically confirmed locally advanced, recurrent (and not a candidate for curative therapy), or metastatic NSCLC. - Evidence of cMET expression by IHC as documented in medical records. - No more than 3 prior lines of systemic therapy including prior cMET targeted ADC or antibody. Part 2 Cohorts A-D - No more than two prior lines of therapy in the locally advanced/metastatic setting. Part 2 Cohorts A-E: - Known to not have an actionable EGFR mutation. Patients with or without other driver mutations are permitted to enroll. - Patients without any actionable gene alteration: must have progressed on (or be considered ineligible for) standard of care therapy - Patients with actionable gene alterations (other than EGFR) must have progressed on (or be considered ineligible for) or be intolerant to anti-cancer therapy targeting driver gene alterations and available standard of care therapy All patients (Part 1 and Part 2) - Patient has at least one measurable lesion per RECIST 1.1 - ECOG performance status 0 or 1 - For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective method of birth control for the duration of the study treatment and for at least 6 months after the last dose of study drug. - Able to provide informed consent, and willing and able to comply with study protocol requirements

• Radiation to the lung within 2 months prior to screening. - Major surgery within 28 days of first dose of study drug administration. - Untreated, uncontrolled CNS metastases. - History of interstitial lung disease or pneumonitis that required treatment with systemic steroids or evidence of active interstitial lung disease or pneumonitis. A history of prior radiation pneumonitis in the radiation field (fibrosis) is permitted. - Clinically significant systemic illness that could pose undue risk to the subject or confound the ability to interpret study results. - Active infection requiring IV antibiotics, antivirals, or antifungal medication - Neuropathy > Grade 1 - History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver disease. - Active or chronic corneal disorder