• Have locally advanced or metastatic non-small cell lung cancer (NSCLC).

• Have c-Met+ NSCLC as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory. Participant must submit archival or fresh tumor material for assessment of c-Met levels during the prescreening period. Tumor material from the primary tumor site and/or metastatic sites are allowed. If archival tissue is negative for c-Met overexpression, subject can submit fresh biopsy material for reassessment of c-Met expression.

• Histologically documented non-squamous epidermal growth factor receptor (EGFR) wild type NSCLC (site documented EGFR status). Of note, subjects with other actionable mutations are eligible as long as EGFR status is known and all other eligibility criteria are met. As of Protocol Version 11, Stage 1 is complete and Stage 2 is enrolling participants with non-squamous EGFR wild type NSCLC only.

• Must have received no more than 2 lines of prior systemic therapy (including no more than 1 line of systemic cytotoxic chemotherapy) in the locally advanced or metastatic setting.

• Multiple lines of tyrosine kinase inhibitors (TKIs) targeting the same tyrosine kinase (TK) count as 1 line of therapy for the purposes of this eligibility criterion.

• Progressed on systemic cytotoxic therapy (or are ineligible for systemic cytotoxic chemotherapy) and an immune checkpoint inhibitor (as monotherapy or in combination with systemic cytotoxic chemotherapy, or ineligible), and prior anticancer therapies targeting driver gene alterations (if applicable).

• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.

• Treatment with any therapies within the noted time intervals is excluded prior to the first dose of telisotuzumab vedotin as noted in the protocol.

• Metastases to the central nervous system (CNS) are eligible only after definitive therapy (such as surgery or radiotherapy) is provided within the protocol.