A Study to Assess Disease Activity of Intravenously (IV) Infused Telisotuzumab Vedotin in Adult Participants With Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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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 determine how telisotuzumab vedotin affects the disease state in adult participants with previously untreated participants with MET amplified non-squamous NSCLC. Change in disease activity will be assessed. Telisotuzumab vedotin is an investigational drug being developed for the treatment of MET amplified non-squamous NSCLC. Participants receive intravenously (IV) infused of telisotuzumab vedotin. Approximately 70 adult participants with previously untreated MET amplified locally advanced/metastatic non-squamous NSCLC will be enrolled in the study in approximately 110 sites worldwide. Participants will receive IV telisotuzumab vedotin every 2 weeks until meeting study drug discontinuation criteria. 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.

Official Title
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Phase 2, Open-Label Study in Subjects With Previously Untreated MET Amplified Locally Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Biological: Telisotuzumab Vedotin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have MET amplification in tumor tissue as determined by the Sponsor-designated central laboratory MET FISH Assay or in plasma and/or tissue by a Sponsor-approved assay. Must have histologically documented non-squamous adenocarcinoma non-small cell lung cancer (NSCLC) that is locally advanced or metastatic. 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 or 1. Participant may have received prior adjuvant/neoadjuvant systemic chemotherapy and/or radiation and/or immunotherapy provided that the subject has not progressed on or within 6 months of completing the regimen and it was completed >= 6 months before subject's first dose of study drug. Metastases to the central nervous system (CNS) are eligible only after definitive therapy is provided as noted in the protocol. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. Exclusion Criteria: Alterations in EGFR, ALK, ROS1, or BRAF that predict sensitivity to available targeted therapy. Participants with other alterations that are candidates for available targeted therapy. Prior systemic therapy for locally advanced/metastatic NSCLC. Of note, limited treatment with no more than 1 cycle of chemotherapy is allowed prior to receiving the first dose of study drug provided there is no evidence of progression. Have a history of other malignancies except those noted in the protocol. Have a 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. Received prior c-Met-targeted antibodies. Have NSCLC that is eligible for treatment with curative intent. Have unresolved adverse events (AEs) >= Grade 2 from prior anticancer therapy, except for alopecia or anemia. Have had major surgery within 21 days prior to the first dose of telisotuzumab vedotin. Have clinically significant condition(s) as noted in the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telisotuzumab Vedotin<br>Participants will receive telisotuzumab vedotin every 2 weeks until meeting study drug discontinuation criteria. | Biological: Telisotuzumab Vedotin<br>* Intravenous (IV) Infusion<br>* Other names: ABBV-399;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) as Assessed by an Independent Central Review (ICR) | ORR will be defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. | Up to 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DoR) | DoR will be defined for confirmed responders as the time from the initial response (CR or PR) to the first occurrence of radiographic progression per RECIST v1.1, or death from any cause. | Up to 1 Year | 
| Disease Control Rate (DCR) | DCR will be defined as the percentage of participants with best overall response of confirmed CR or confirmed PR, or stable disease (SD) for at least 12 weeks following first dose of study drug, based on RECIST, version 1.1. | Up to 1 Year | 
| Progression Free Survival (PFS) per ICR | PFS will be defined as the time from the participant's first dose of study drug to the first occurrence of radiographic progression based on RECIST, version 1.1 or death from any cause. | Up to 1 Year | 
| Overall Survival (OS) | OS will be defined as the time from participant's first dose of study drug to the event of death from any cause. | Up to 2 Years | 
| Time to Deterioration in Cough | Time to deterioration in cough as measured by the cough items of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (EORTC QLQ-LC13). | Up to 1 Year | 
| Time to Deterioration in Pain | Time to deterioration in pain as measured by the cough items of the EORTC QLQ-LC13. | Up to 1 Year | 
| Time to Deterioration in Dyspnea | Time to deterioration in dyspnea as measured by the cough items of the EORTC QLQ-LC13. | Up to 1 Year | 
| Time to Deterioration of Physical Functioning | Time to deterioration of physical functioning as measured by the physical functioning domain of the EORTC-QLQ-Core 30 (EORTC QLQ-C30). | Up to 1 Year | 
| Change from Baseline in Quality of Life as measured by the Global Health Status/Quality of Life Domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). | The EORTC QLQ-C30 assesses health-related quality of life in cancer patients participating in clinical trials. The EORTC QLQ-C30 comprises 5 functional scales (physical, role, emotional, social, cognitive), 8 single-item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, and dyspnea), as well as subscales assessing global health/quality of life and financial impact. Raw scores are transformed to a scale of 0 to 100, with higher scores representing better functioning/quality of life and greater symptom burden. | Up to 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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c-Met NSCLC, Telisotuzumab Vedotin, ABBV-399, Cancer, Non Small Cell Lung Cancer, NSCLC, MET Amplified NSCLC