A Study to Assess Adverse Events and How Intravenously (IV) Infused Telisotuzumab Vedotin (ABBV-399) Moves Through the Body as a Monotherapy in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-small cell lung cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. The purpose of this study is to assess how safe telisotuzumab vedotin is in adult participants with NSCLC. Change in disease activity and adverse events will be assessed.

Telisotuzumab vedotin is an investigational drug being developed for the treatment of NSCLC. Participants will be randomly assigned a treatment of Teliso-V in 1 of 2 arms at an 1:1 ratio. Each group receives intravenous (IV) infusion of telisotuzumab vedotin. Approximately 100 adult participants with c-Met overexpressing NSCLC will be enrolled in the study at approximately 40 sites worldwide.

Participants will receive IV telisotuzumab vedotin at 1 of 2 doses as part of a 3 year study duration.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.


Eligibility Criteria:
Inclusion Criteria:

* Projected life expectancy of at least 12 weeks.
* Must have c-Met overexpressing non-small cell lung cancer (NSCLC) as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory
* Must have histologically or cytologically documented NSCLC that is locally advanced or metastatic.
* Must have a known epidermal growth factor receptor (EGFR) activating mutation status.
* Actionable alterations in genes other than EGFR are permitted.
* Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
* Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
* Must have received no more than 1 line of prior systemic cytotoxic chemotherapy in the locally advanced or metastatic setting, as stated in the protocol.
* Must have progressed on at least 1 line of prior therapy for locally advanced/metastatic NSCLC, as stated in the protocol.

Exclusion Criteria:

* Adenosquamous or neuroendocrine histology, or sarcomatoid features.
* Actionable EGFR activating mutations.
* Received prior c-Met-targeted antibodies, prior telisotuzumab vedotin, or prior antibody-drug conjugates either targeting c-Met or consisting of monomethylauristatin E.
* Received prior docetaxel therapy.
* Metastases to the central nervous system (CNS) are eligible only after adequate treatment (such as surgery or, radiotherapy, or drug therapy) is provided, as stated on the protocol.
* History of other malignancies except those stated in the protocol.
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan, as noted in the protocol.
* Unresolved clinically significant adverse event (AE) \>= Grade 2 from prior anticancer therapy, except for alopecia or anemia. Participants with hormone deficiencies caused by prior anticancer therapy who are asymptomatic and on a stable dose of replacement hormone are eligible for study.
* Major surgery within 21 days prior to randomization.
* Clinically significant condition(s) including but not limited to those listed in the protocol.
* Clinically significant liver disease, including hepatitis, current alcohol abuse, or cirrhosis.
* Grade \>= 2 edema or lymphedema.
* Grade \>= 2 ascites or pleural effusion.
* Grade \>= 2 neuropathy.
* Active uncontrolled bacterial or viral infection.
* Active corneal disorder.