A Phase 3 Open-Label, Randomized, Controlled, Global Study of Telisotuzumab Vedotin (ABBV-399) Versus Docetaxel in Subjects With Previously Treated c-Met Overexpressing, EGFR Wildtype, Locally Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer

Plain English Summary

A Study to Assess Disease Activity and Adverse Events of Intravenous (IV) Telisotuzumab Vedotin Compared to IV Docetaxel in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC) is a Phase 3 clinical trial sponsored by AbbVie studying Non Small Cell Lung Cancer. This trial tests a new drug, telisotuzumab vedotin, against a standard chemotherapy, docetaxel, for a specific type of lung cancer. It is for adults with non-squamous non-small cell lung cancer (NSCLC) that has spread and has previously been treated. Participants will receive either the new drug or docetaxel through an IV infusion and will have regular clinic visits for assessments. Standard treatment options for this stage of lung cancer include chemotherapy and immunotherapy, depending on specific genetic markers. The trial aims to enroll 698 participants.

Official Summary

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 if telisotuzumab vedotin works better than docetaxel and to assess how safe telisotuzumab vedotin is in adult participants with NSCLC who have previously been treated. 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 or Docetax at an 1:1 ratio. Each group receives intravenous (IV) infusion of telisotuzumab vedotin or IV infusion of docetaxel. Approximately 698 adult participants with c-Met overexpressing NSCLC will be enrolled in the study in approximately 330 sites worldwide. Participants will receive IV telisotuzumab vedotin every 2 weeks or docetaxel every 3 weeks until meeting study drug discontinuation criteria. At the conclusion of the study, participants who continue to demonstrate clinical benefit may be eligible to receive study treatment via an extension of the study, a rollover study, or through another mechanism. 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with non-squamous NSCLC that has spread and has specific genetic markers (c-Met overexpression, no EGFR mutations). Patients who have had no more than one prior chemotherapy treatment for advanced or metastatic disease. Individuals with a life expectancy of at least 12 weeks and a good general health status (ECOG 0-1). Patients with brain metastases are eligible if they are stable and have been adequately treated. This trial is studying Non Small Cell Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The trial will measure how long patients live without their cancer getting worse (Progression-Free Survival) and how long they live overall (Overall Survival), indicating how effective the new drug is The specific primary outcome measures are: Progression-Free Survival (PFS) per Blinded Independent Central Review (BICR) (Up to approximately 39 months); Overall Survival (OS) (Up to approximately 39 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a need for new treatments in lung cancer patients whose tumors overexpress c-Met, a protein that can drive cancer growth, offering a potential new option beyond standard chemother As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Non Small Cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This Phase 3 trial for a targeted therapy in a specific lung cancer subtype signals a significant investment in a potentially competitive market, with approval probability dependent on demonstrating s Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 698 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if your cancer has c-Met overexpression and if you meet the other eligibility criteria. Be prepared for regular visits to the clinic for IV infusions, blood tests, scans, and to report any side effects. The study involves receiving either the investigational drug or docetaxel until the cancer progresses or side effects become too severe. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 698 participants

Interventions

• BIOLOGICAL: Telisotuzumab Vedotin — Intravenous (IV) Infusion
• DRUG: Docetaxel — IV Infusion

Primary Outcomes

• Progression-Free Survival (PFS) per Blinded Independent Central Review (BICR) (Up to approximately 39 months)
• Overall Survival (OS) (Up to approximately 39 months)

Secondary Outcomes

• Objective Response Rate (ORR), per BICR. (Up to approximately 58.25 months)
• Duration of Response (DoR), per BICR (Up to approximately 58.25 months)
• PFS per Investigator Assessment (Up to approximately 58.25 months)
• Change from Baseline of Physical Functioning as measured by the Physical Functioning domain of the EORTC-QLQ-Core 30 (EORTC QLQ-C30). (Up to approximately 12 Weeks)
• Change from Baseline in Quality of Life as measured by the Global Health Status/Quality of Life Domain of the EORTC QLQ-C30. (Up to approximately 12 Weeks)

Full Eligibility Criteria

Inclusion Criteria:

* Projected life expectancy of at least 12 weeks.
* Participants must have c-Met overexpressing non-small cell lung cancer (NSCLC) as assessed by an AbbVie designated immunohistochemistry (IHC) laboratory using the VENTANA MET (SP44) RxDx assay.
* Archival or fresh tumor material must be submitted for assessment of c-Met protein expression levels during the Pre-Screening period. Tumor material from the primary tumor site and/or metastatic sites are allowed.

  * If a participant was prescreened for Study M14-239 but did not enroll, tumor material previously submitted for Study M14-239 may be used for Study M18-868 Pre-Screening upon confirmation from AbbVie that sufficient evaluable tumor material is available (Except China).
* A histologically or cytologically documented non-squamous cell NSCLC that is locally advanced or metastatic.
* A known epidermal growth factor receptor (EGFR) activating mutation status.

  \-- Participants with actionable EGFR activating mutations are not eligible
* Actionable alterations in genes other than EGFR are eligible.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
* An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
* Have received no more than 1 line of prior systemic cytotoxic chemotherapy in the locally advanced or metastatic setting.

  * Neoadjuvant and adjuvant systemic cytotoxic chemotherapy will count as a prior line for eligibility purposes if progression occurred within 6 months of the end of therapy.
* Have progressed on at least 1 line of prior therapy for locally advanced/metastatic NSCLC:

  * Participants WITHOUT an actionable gene alteration: must have progressed on (or be considered ineligible for) platinum-based chemotherapy and immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy).
  * Participants WITH an actionable gene alteration for which immune checkpoint inhibitor therapy is not standard of care (e.g., anaplastic lymphoma kinase \[ALK\] translocation): must have progressed on (or be considered ineligible for) anti-cancer therapy targeting driver gene alterations and platinum-based chemotherapy.

    * Participants with actionable gene alterations for which immune checkpoint inhibitor is standard of care must have also progressed on (or be considered ineligible for) immune checkpoint inhibitor (as monotherapy or in combination with chemotherapy).
* Must be considered appropriate for docetaxel therapy based on the assessment of the treating physician.
* Participants with metastases to the central nervous system (CNS) are eligible only after adequate treatment (such as surgery, radiotherapy, or drug therapy) is provided and:

  * They are asymptomatic and off or on a stable or reducing dose of systemic steroids (on no more than 10 mg per day \[QD\] prednisone or equivalent) and/or anticonvulsants for at least 2 weeks prior to randomization.

Exclusion Criteria:

* Evidence of new, untreated CNS metastases or progressing CNS metastases after treatment.
* Evidence of leptomeningeal disease.
* Participants with adenosquamous or neuroendocrine histology, nor sarcomatoid features.
* Epidermal growth factor receptor (EGFR) activating mutations.
* Participants who have received prior c-Met-targeted antibodies, prior telisotuzumab vedotin, or prior antibody-drug conjugates either targeting c-Met or consisting of monomethylauristatin E..
* Participants who have received prior docetaxel therapy.
* A history of other malignancies except:

  * 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. Additionally, participants must not be receiving any ongoing anti-cancer therapy, including maintenance therapy, prior to randomization..
  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  * Adequately treated carcinoma in situ without current evidence of disease.
* 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. A history of prior radiation pneumonitis in the radiation field (fibrosis) is not permitted.
* Unresolved or neuroendocrine histology, nor sarcomatoid features 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) as listed in the protocol.

Trial Locations

• University of Alabama at Birmingham - Main /ID# 247074, Birmingham, Alabama, United States
• Ironwood Cancer & Res Ctr /ID# 262446, Chandler, Arizona, United States
• Mayo Clinic Arizona /ID# 255858, Phoenix, Arizona, United States
• Onvida Health Yuma Medical Center /ID# 253625, Yuma, Arizona, United States
• City of Hope /ID# 243157, Duarte, California, United States
• City Of Hope - Seacliff /ID# 263143, Huntington Beach, California, United States
• City of Hope - Orange County Lennar Foundation Cancer Center /ID# 263144, Irvine, California, United States
• City Of Hope - Antelope Valley /ID# 263138, Lancaster, California, United States
• The Oncology Institute Of Hope & Innovation -East Los A /ID# 239774, Los Angeles, California, United States
• University of California, Los Angeles /ID# 253954, Los Angeles, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer
• Lung Cancer
• Metastatic Lung Cancer
• Advanced Lung Cancer
• EGFR-mutated NSCLC
• ALK-positive NSCLC
• Chemotherapy-resistant Lung Cancer
• Targeted Cancer Therapy
• Oncology
• Cancer Research

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