Phase 2 Open-Label Study on Safety and Efficacy of Telisotuzumab Vedotin in c-Met Positive Non-Small Cell Lung Cancer Patients with Prior Treatment

Trial ID: 2023-507902-15-00
Protocol: M14-239
Sponsor: AbbVie Deutschland GmbH & Co. KG

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Diseases & Conditions

Non-small cell lung cancer

Objectives

The primary objective of this Phase 2, open-label study is to determine the **overall response rate (ORR)** of telisotuzumab vedotin in subjects with c-Met+ **Non-Small Cell Lung Cancer (NSCLC)**. This is clinically relevant as it evaluates the efficacy of telisotuzumab vedotin in targeting c-Met+ NSCLC, a subtype of lung cancer with limited treatment options. Additionally, for the Monotherapy Cohort dosed at 1.6 mg/kg every two weeks (Q2W), the primary objective is to evaluate the safety and tolerability of telisotuzumab vedotin monotherapy, which is crucial for assessing the risk-benefit profile of the treatment.

The secondary objectives for Stage 1 and Stage 2 include determining the **duration of response (DoR)**, **disease control rate (DCR)**, **progression-free survival (PFS)**, **overall survival (OS)**, and evaluating the safety and tolerability of the treatment. For the Monotherapy Cohort 1.6 mg/kg Q2W, the secondary objective is to evaluate the preliminary efficacy of telisotuzumab vedotin monotherapy. These secondary objectives provide comprehensive insights into the treatment's effectiveness and safety, contributing to a better understanding of its potential clinical benefits and limitations.

Participants

The clinical trial involves a total of **203 participants** diagnosed with **Non-Small Cell Lung Cancer (NSCLC)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including a histologically confirmed diagnosis of non-squamous NSCLC with known epidermal growth factor receptor (EGFR) status and c-Met positivity. The trial includes individuals who have locally advanced or metastatic NSCLC and have progressed on or are ineligible for systemic cytotoxic chemotherapy and immune checkpoint inhibitors. Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial population also includes vulnerable groups, although specific lifestyle considerations such as diet or physical activity are not detailed. Key inclusion criteria require participants to have received no more than two lines of prior systemic therapy in the advanced setting and to have no known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The selection process ensures that participants meet these stringent criteria to evaluate the safety and efficacy of telisotuzumab vedotin in this specific patient population.

Plans and Procedures

The clinical trial is a **Phase 2, open-label study** designed to evaluate the safety and efficacy of **Telisotuzumab Vedotin** in subjects with previously treated **c-Met+ Non-Small Cell Lung Cancer (NSCLC)**. The primary objective is to determine the overall response rate (ORR) of Telisotuzumab Vedotin in this patient population. The trial is structured to include a monotherapy cohort where the drug is administered at a dose of 1.6 mg/kg every two weeks (Q2W) via **intravenous administration**. The study is not categorized as low intervention and is expected to conclude by January 2025, with recruitment having commenced in July 2019.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed NSCLC, c-Met positivity, and prior treatment history. The trial includes follow-up visits to monitor safety, tolerability, and efficacy outcomes, with assessments of primary and secondary endpoints such as duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The end-of-study visit will conclude the participant's involvement, which is anticipated to last up to 24 months, depending on individual response and tolerability.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. Additionally, failure to meet the SARS-CoV-2 infection eligibility criteria or other protocol-specified conditions may also result in early termination from the study. The trial is conducted under the sponsorship of AbbVie Deutschland GmbH & Co. KG, with Telisotuzumab Vedotin provided as a solution for injection. The study is designed to ensure rigorous monitoring and data collection to achieve its objectives and contribute valuable insights into the treatment of c-Met+ NSCLC.

Treatment

The clinical trial involves the administration of **Telisotuzumab Vedotin**, an investigational medication, to evaluate its safety and efficacy in subjects with previously treated c-Met+ non-small cell lung cancer (NSCLC). **Telisotuzumab Vedotin** is provided as a **solution for injection** and is administered via **intravenous administration**. The dosing regimen for the monotherapy cohort is set at 1.6 mg/kg every two weeks (Q2W). The maximum daily dose is 1.9 mg/kg, with a total maximum dose of 98.8 mg/kg over the treatment period. The treatment duration is capped at 24 weeks. The active substance, **Telisotuzumab Vedotin**, is a protein-based compound, specifically categorized under "Protein - Other". The pharmaceutical product is developed and supplied by AbbVie Deutschland GmbH & Co. KG, under the sponsor product code ABBV-399.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is designed as an open-label study, meaning that both the researchers and participants are aware of the treatment being administered. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol. The primary objective is to determine the overall response rate (ORR) of **Telisotuzumab Vedotin** in the specified patient population, with a focus on evaluating the safety and tolerability of the monotherapy regimen.

Efficacy

The efficacy of Telisotuzumab Vedotin in the clinical trial will be assessed primarily through the **Overall Response Rate (ORR)** in subjects with c-Met+ Non-Small Cell Lung Cancer (NSCLC). This primary endpoint will evaluate the proportion of patients who achieve a complete or partial response to the treatment. Secondary endpoints include the **Duration of Response (DoR)**, **Disease Control Rate (DCR)**, **Progression-Free Survival (PFS)**, and **Overall Survival (OS)**. These parameters will provide a comprehensive evaluation of the treatment's efficacy over time.

Data collection for these endpoints will be conducted at specified intervals throughout the trial. The ORR will be determined by assessing tumor response using imaging techniques and clinical evaluations. The DoR will measure the time from the initial response to disease progression or relapse. DCR will be calculated based on the percentage of patients who achieve stable disease, partial response, or complete response. PFS will track the time from treatment initiation to disease progression or death, while OS will measure the time from treatment initiation to death from any cause.

These efficacy assessments will be conducted using validated methods and tools, ensuring the reliability and accuracy of the data collected. The trial is designed to provide robust evidence on the efficacy of Telisotuzumab Vedotin in treating c-Met+ NSCLC, contributing valuable insights into its potential therapeutic benefits.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Histologically confirmed non-small cell lung cancer (NSCLC) with known non squamous epidermal growth factor receptor (EGFR) status (wild type; with site documented status). Subjects in Monotherapy Cohort 1.6 mg/kg Q2W must have non-squamous EGFR wild type NSCLC.
Has locally advanced or metastatic NSCLC.
Has c-Met+ NSCLC as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory. Subject 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, fresh biopsy material may be submitted for reassessment of c-Met expression. "
If a subject meets eligibility criteria for c-Met protein expression level based on archival tumor material, fresh tumor material for assessment of c-Met expression levels should be submitted prior to dosing of telisotuzumab vedotin. If it is determined that a pre-dose fresh biopsy is not appropriate for a given subject, the subject may still be enrolled at the investigator's discretion. AbbVie must be informed of this decision before dosing. "
Subjects who have progressed on systemic cytotoxic chemotherapy (or are ineligible for systemic cytotoxic chemotherapy) and an immune checkpoint inhibitor (as monotherapy or in combination with systemic cytotoxic chemotherapy, or ineligible for an immune checkpoint inhibitor), and prior anti-cancer therapies targeting driver gene alterations (if applicable).
Subject must have received no more than 2 lines of prior systemic therapy (including no more than 1 line of prior systemic cytotoxic chemotherapy) in the locally advanced or metastatic setting.
Subjects should not have received prior cMET-targeted antibody therapies.
Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
No known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection, the subject must have a negative molecular (e.g., polymerase chain reaction [PCR]) test result or 2 negative antigen test results at least 24 hours apart. "
Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria: - At least 10 days since first positive test result has passed in asymptomatic patients or at least 10 days since recovery, defined as resolution of fever without use of antipyretics and improvement in symptoms. "

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Exclusion Criteria

Has adenosquamous histology.
Subjects with metastases to the central nervous system (CNS) are eligible only after definitive therapy (such as surgery or radiotherapy) is provided and: There is no evidence of progression of CNS metastases at least 2 weeks after definitive therapy. -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. "
Has a clinically significant condition(s) described in the protocol.
Has unresolved clinically significant adverse events >= grade 2 from prior anticancer therapy, except for alopecia or anemia. "
Had major surgery within 21 days prior to the first dose of telisotuzumab vedotin. "
Subject must not have a history of interstitial lung disease or pneumonitis that required treatment with systemic steroids. "
Subjects must not have any evidence of pulmonary fibrosis on screening imaging assessment or any history of pneumonitis or interstitial lung disease within 3 months of the planned first dose of the study drug. For imaging findings deemed clinically insignificant by the treating physician, subject may be eligible after discussion with and approval from the AbbVie medical monitor. "
For Sites in Ireland Only: Subjects must not have any evidence of pulmonary fibrosis on screening imaging assessment or any history of pneumonitis or ILD. For imaging findings deemed clinically insignificant by the treating physician, subject may be eligible after discussion with and approval from the AbbVie medical monitor. "
Subjects must not have received radiation therapy to the lung <6 months prior to the first dose of telisotuzumab vedotin. "
Subjects must not have received any live vaccine within 30 days of the first dose of investigational product.
For Sites in France and Czech Republic Only: Subjects must not have known human immunodeficiency virus (HIV) infection. Note: HIV testing is not required for eligibility for this protocol unless mandated by local regulatory authority or ethics committee/institutional review board."
For Sites in France and Czech Republic Only: Subjects must not have Active hepatitis B virus (HBV) infection, defined by hepatitis B surface antigen (HBsAg) positivity or HBV DNA ≥ 500 IU/mL. In subjects with known HBV infection, the presence of active infection must be tested locally. If HBV status is unknown, it must be tested locally at screening.
For Sites in France and Czech Republic Only: Subjects must not have Active hepatitis C virus (HCV) infection, defined by HCV RNA positivity. Subjects cured of HCV infection may be included in the study. In subjects with known HCV infection, the presence of active infection must be tested locally. If HCV status is unknown, it must be tested locally at screening. "
For Sites in France and Czech Republic Only: Subjects must not have Uncontrolled autoimmune disease.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Recruiting	08 Jul 2019	13
France	Not Recruiting	08 Jul 2019	18
Germany	Not Recruiting	08 Jul 2019	5
Greece	Not Recruiting	08 Jul 2019	3
Ireland	Not Recruiting	08 Jul 2019	1
Italy	Not Recruiting	08 Jul 2019	8
Romania	Not Recruiting	08 Jul 2019	8
Spain	Not Recruiting	08 Jul 2019	11