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

Trial ID: 2022-500608-23-00
Protocol: M22-137
Sponsor: AbbVie Deutschland GmbH & Co. KG

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Diseases & Conditions

Non-small cell lung cancer

Objectives

The primary objective of this study is to determine the **objective response rate (ORR)** of telisotuzumab vedotin in subjects with previously untreated MET amplified non-squamous non-small cell lung cancer (NSCLC). This is clinically relevant as it evaluates the efficacy of telisotuzumab vedotin in inducing a measurable response in this specific patient population, which could inform treatment decisions and improve patient outcomes.

Secondary objectives include:

Determine duration of response (DoR)
Determine disease control rate (DCR)
Determine progression-free survival (PFS)
Determine overall survival (OS)
Determine time to deterioration in cough, pain, or dyspnea as measured by the EORTC QLQ-LC13
Determine time to deterioration of physical functioning as measured by the EORTC QLQ-C30
Determine change from baseline in quality of life as measured by the global health status/quality of life domain of the EORTC QLQ-C30
Determine safety and tolerability

These secondary objectives aim to provide a comprehensive assessment of the treatment's impact on disease progression, patient quality of life, and overall safety profile, which are critical for understanding the broader implications of telisotuzumab vedotin therapy in this patient group.

Participants

The clinical trial involves a total of **48 participants** diagnosed with **previously untreated MET amplified locally advanced/metastatic non-squamous non-small cell lung cancer**. The study population includes both male and female adults, aged 18 years and older, who have been confirmed to have MET amplification in tumor tissue or plasma. Participants were selected based on specific criteria, including having a histologically documented non-squamous adenocarcinoma NSCLC that is either locally advanced or metastatic, and possessing measurable disease as per RECIST version 1.1. The trial includes individuals with an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, and those with central nervous system metastases are eligible following definitive therapy, provided they meet certain conditions regarding symptom management and medication stability. The trial population also considers vulnerable groups, ensuring comprehensive representation. Lifestyle factors such as diet and physical activity are not specified, and the trial does not focus on any particular lifestyle considerations.

Plans and Procedures

The clinical trial is a **Phase 2, open-label study** designed to evaluate the efficacy of **telisotuzumab vedotin** in adult participants with previously untreated **MET amplified locally advanced/metastatic non-squamous non-small cell lung cancer (NSCLC)**. The primary objective is to determine the objective response rate (ORR) of the investigational product. Secondary endpoints include duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and changes in quality of life as measured by specific domains of the EORTC QLQ-C30 and QLQ-LC13. The trial is expected to run from January 2023 to December 2026.

The study follows a structured sequence of visits, beginning with an inclusion (screening) visit where eligibility is confirmed based on criteria such as age, MET amplification status, and performance status. Participants must have histologically documented non-squamous adenocarcinoma NSCLC that is locally advanced or metastatic, and measurable disease per RECIST version 1.1. Follow-up visits are scheduled to monitor the participants' response to treatment and assess any adverse events. The end-of-study visit will conclude the trial for each participant, evaluating the overall outcomes and collecting final data.

Participants are expected to be involved in the study for a maximum treatment period of 24 months, with the possibility of early termination if they experience unacceptable toxicity, disease progression, or withdrawal of consent. The trial employs a controlled design, with **telisotuzumab vedotin** administered via intravenous infusion. The study is not a low-intervention trial, and it does not include a pediatric formulation. Participants with CNS metastases are eligible only after definitive therapy and must meet specific criteria regarding symptom management and medication stability.

Treatment

The clinical trial involves the administration of **Telisotuzumab Vedotin**, an experimental medication, to evaluate its efficacy in subjects with previously untreated MET amplified locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). **Telisotuzumab Vedotin** is provided in the form of a **solution for injection** and is administered via **intravenous infusion**. The dosing regimen is specified in **milligrams per kilogram (mg/kg)**, although the exact dosage is not detailed in the provided data. The treatment period is set for a maximum of 24 weeks. The active substance, **Telisotuzumab Vedotin**, is a protein-based compound, classified under the category "Protein - Other". The pharmaceutical product is developed and supplied by **ABBVIE DEUTSCHLAND GMBH & CO. KG**.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The trial is designed to assess the objective response rate (ORR) of **Telisotuzumab Vedotin** in the specified patient population. Participant compliance with the dosing schedule will be monitored throughout the study duration to ensure adherence to the treatment protocol. The trial does not include a pediatric formulation, and the product is not classified as an orphan drug. The study is conducted under the authorization of the relevant regulatory bodies, as indicated by the product's authorization status.

Efficacy

The efficacy of Telisotuzumab Vedotin in the treatment of **non-squamous non-small cell lung cancer (NSCLC)** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the Objective Response Rate (ORR), which will be evaluated by an independent central review (ICR). This measure will determine the proportion of patients who experience a predefined level of tumor size reduction.

Secondary endpoints include the Duration of Response (DoR), Disease Control Rate (DCR), Progression-Free Survival (PFS) as assessed by ICR, and Overall Survival (OS). Additionally, patient-reported outcomes will be measured, such as the time to deterioration in symptoms like cough, pain, and dyspnea, using the European Organization for Research and Treatment of Cancer Lung Cancer Module 13 (EORTC QLQ-LC13). The time to deterioration of physical functioning will be assessed using the physical functioning domain of the EORTC QLQ-Core 30 (EORTC QLQ-C30), and changes from baseline in quality of life will be measured by the global health status/quality of life domain of the EORTC QLQ-C30.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Subjects must have completed an informed consent.
Subject must be an adult, at least 18 years old.
Subject 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. Where confirmed as a local requirement, the central assay can only be utilized after IVDR certification is obtained.
Subject must have histologically documented non-squamous adenocarcinoma NSCLC that is locally advanced or metastatic.
Subject must have measurable disease per RECIST version 1.1.
Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Subjects with metastases to the central nervous system (CNS) are eligible only after definitive therapy (such as surgery or radiotherapy) is provided and: 1) There is no evidence of progression of CNS metastases at least 2 weeks after definitive therapy. 2) They are asymptomatic and off or on a stable or reducing dose of systemic steroids and/or anticonvulsants for at least 2 weeks prior to first dose of telisotuzumab vedotin.
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

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Exclusion Criteria

Subject must not have clinically significant condition(s) including but not limited to the following: 1) Clinically significant vascular disease, including: Myocardial infarction within 1 year or stroke within 6 months prior to first dose of study drug, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III – IV), cardiac arrhythmia (CTCAE Version 5 Grade 2 or higher), or clinically significant electrocardiogram (ECG) abnormalities. 2) Clinically significant liver disease, including hepatitis, current alcohol abuse, or cirrhosis. 3) Grade ≥ 2 edema or lymphedema. 4) Grade ≥ 2 ascites or pleural effusion. 5) Grade ≥ 2 neuropathy. 6) Active uncontrolled bacterial or viral infection.
Subjects with alterations in EGFR, ALK, ROS1, or BRAF that predict sensitivity to available targeted therapy are not eligible. Subjects with other alterations that are candidates for available targeted therapy are not eligible.
Subject must have no prior systemic therapy for locally advanced/metastatic NSCLC. 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. Subject 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.
Subject must not have received prior c-Met-targeted antibodies.
Subject must not have NSCLC that is eligible for treatment with curative intent.
Subjects must not have a history of other malignancies except: 1) Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before the first dose of study drug and felt to be at low risk for recurrence by investigator. 2) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. 3) Adequately treated carcinoma in situ without current evidence of disease.
Subject must not 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.
Subject must not have unresolved adverse events (AEs) ≥ Grade 2 from prior anticancer therapy, except for alopecia or anemia.
Subject must not have had major surgery within 21 days prior to the first dose of telisotuzumab vedotin.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
France	Not Recruiting	01 Jan 2023	3
Germany	Not Recruiting	01 Jan 2023	3
Italy	Not Recruiting	01 Jan 2023	5
Romania	Not Recruiting	01 Jan 2023	4
Spain	Not Recruiting	01 Jan 2023	5