RecruitingInterventionalPhase 2

A Phase 2, Open-Label, Randomized, Global Study of Three Telisotuzumab Vedotin Regimens in Subjects With Previously Treated c-Met Overexpressing, EGFR Wildtype, Locally Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer

NCT ID: NCT06568939Sponsor: AbbVieLast updated: 2026-06-18

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 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 telisotuzumab vedotin in 1 of 3 arms at an 1:1:1 ratio. Each group receives intravenous (IV) infusion of telisotuzumab vedotin at different doses. Approximately 150 adult participants with c-Met overexpressing NSCLC will be enrolled in the study at approximately 80 to 90 sites worldwide. Participants will receive IV telisotuzumab vedotin at 1 of 3 dose regimens 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.

Arms & interventions

DrugTelisotuzumab Vedotin
Intravenous (IV) Infusion

Outcome measures

Primary

Percentage of Participants with Treatment-Emergent Adverse Events (AE)s (Any-grade and Grade >= 2)
An AE is defined as any untoward medical occurrence, inappropriate participant management decision, unintended disease or injury or any untoward clinical signs (including an abnormal laboratory finding) in participants, users or other persons whether or not related to the investigational medical device.
Time frame: Up to Approximately 3 Years
Percentage of Participants with Treatment-Emergent Interstitial Lung Disease (ILD)
ILD is defined by ILD standardized MedDRA query (SMQ) (broad) per investigator and determined per adjudication (any-grade and Grade \>= 2).
Time frame: Up to Approximately 3 Years
Percentage of Participants with Treatment-Emergent Peripheral Neuropathy
Peripheral neuropathy is defined by peripheral neuropathy SMQ (narrow) (any-grade and Grade \>= 2)
Time frame: Up to Approximately 3 Years
Percentage of Participants with Treatment-Emergent Ocular Surface Disorders
Treatment-emergent ocular surface disorders defined by corneal epitheliopathy company MedDRA query (CMQ) (any-grade and Grade \>= 2).
Time frame: Up to Approximately 3 Years
Percentage of Participants with Treatment-Emergent AEs Leading to Study Drug Discontinuation
An AE is defined as any untoward medical occurrence, inappropriate participant management decision, unintended disease or injury or any untoward clinical signs (including an abnormal laboratory finding) in participants, users or other persons whether or not related to the investigational medical device.
Time frame: Up to Approximately 3 Years
Percentage of Participants with Grade 5 Treatment-Emergent AEs
An AE is defined as any untoward medical occurrence, inappropriate participant management decision, unintended disease or injury or any untoward clinical signs (including an abnormal laboratory finding) in participants, users or other persons whether or not related to the investigational medical device.
Time frame: Up to Approximately 3 Years
Objective Response (OR) by Blinded Independent Central Review (BICR)
OR will be defined as achieving confirmed complete response (CR) or confirmed partial response (PR) based on response evaluation criteria in solid tumors (RECIST), version 1.1.
Time frame: Up to Approximately 3 Years

Secondary

Concentrations of Telisotuzumab Vedotin Conjugate in Serum
Time frame: Up to 26 Weeks
Concentrations of Monomethylauristatin E (MMAE) Payload in Plasma
Time frame: Up to 26 Weeks
Percentage of Participants with Antidrug Antibodies (ADAs) of Telisotuzumab Vedotin
Time frame: Up to 26 Weeks
Percentage of Participants with Neutralizing Antidrug Antibodies (nADAs) of Telisotuzumab Vedotin
Time frame: Up to 26 Weeks
Change in Selected items of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Time frame: Cycle 1: Day 1, Day 8, Cycle 2 D1 and D1 of Every Even Cycle Thereafter, Through 3 Years
Change in GP5 item of the Functional Assessment of Cancer Therapy-General (FACT-G)
Time frame: Cycle 1: Day 1, Day 8, Cycle 2 D1 and D1 of Every Even Cycle Thereafter, Through 3 Years
Duration of Response (DoR) by BICR
Time frame: Up to Approximately 3 Years
Progression-Free Survival (PFS) by BICR
Time frame: Up to Approximately 3 Years
Overall Survival (OS)
Time frame: Up to Approximately 3 Years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: * Projected life expectancy of at least 12 weeks. * Must have c-Met overexpressing non-small cell lung cancer (NSCLC) (defined as \>= 25% tumor cells with 3+ staining (high \[\>= 50% 3+\]; intermediate \[\>= 25% - \< 50%\]) as assessed by a Sponsor 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. * EGFR activating mutations (e.g., EGFR Exon 19 deletions, T790M, Exon 21 L858R, or Exon 20 insertion 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). Participants with CNS metastases 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.

Study locations (38)

Ironwood Cancer and Research Center /ID# 276370

Chandler, Arizona, 85224

Recruiting

University of Arkansas for Medical Sciences /ID# 272923

Little Rock, Arkansas, 72205

Recruiting

Valkyrie Clinical Trials /ID# 271322

Los Angeles, California, 90067

Recruiting

Yale New Haven Hospital /ID# 271584

New Haven, Connecticut, 06510

Recruiting

Cancer Specialists of North Florida - Jacksonville - AC Skinner Parkway /ID# 270899

Jacksonville, Florida, 32256

Recruiting

Ocala Oncology Center /ID# 273697

Ocala, Florida, 34474

Recruiting

Memorial Hospital West /ID# 270313

Pembroke Pines, Florida, 33028

Recruiting

Comprehensive Hematology Oncology /ID# 270422

St. Petersburg, Florida, 33701-4732

Recruiting

Florida Cancer Specialists - North /ID# 271995

St. Petersburg, Florida, 33705

Recruiting

Florida Cancer Specialists - East /ID# 271993

West Palm Beach, Florida, 33401

Recruiting

University Cancer & Blood Center /ID# 270969

Athens, Georgia, 30607

Recruiting

Northwest Georgia Oncology Centers /ID# 275374

Marietta, Georgia, 30060

Recruiting

Memorial University Medical Center /ID# 272467

Savannah, Georgia, 31404

Recruiting

Kaiser Permanente Moanalua Medical Center /ID# 272916

Honolulu, Hawaii, 96819

Recruiting

University of Illinois Hospital and Health Sciences System /ID# 275345

Chicago, Illinois, 60607

Recruiting

Illinois Cancer Specialists /ID# 274678

Niles, Illinois, 60714

Recruiting

Springfield Clinic - First /ID# 272576

Springfield, Illinois, 62702

Recruiting

Nebraska Hematology-Oncology /ID# 272970

Lincoln, Nebraska, 68506

Recruiting

Nebraska Cancer Specialists - Omaha - Wright Street /ID# 271527

Omaha, Nebraska, 68130

Recruiting

Renown Regional Medical Center /ID# 273535

Reno, Nevada, 89502

Recruiting

Astera Cancer Care /ID# 272359

East Brunswick, New Jersey, 08816-4096

Recruiting

Regional Cancer Care Associates /ID# 270783

Teaneck, New Jersey, 07666

Recruiting

Montefiore Medical Center - Einstein Campus /ID# 277169

The Bronx, New York, 10461

Recruiting

Clinical Research Alliance - Westbury /ID# 270455

Westbury, New York, 11590

Recruiting

FirstHealth of the Carolinas- Speciality Center /ID# 272924

Pinehurst, North Carolina, 28374

Recruiting

Mercy Health - Perrysburg Cancer Center /ID# 270536

Perrysburg, Ohio, 43551

Recruiting

Genesis Healthcare System /ID# 273361

Zanesville, Ohio, 43701

Recruiting

Guthrie Robert Packer Hospital /ID# 270316

Sayre, Pennsylvania, 18840

Recruiting

Cancer Care Associates Of York /ID# 270971

York, Pennsylvania, 17403

Recruiting

Medical University of South Carolina /ID# 273272

Charleston, South Carolina, 29425

Recruiting

Saint Francis Cancer Center - Greenville /ID# 276368

Greenville, South Carolina, 29607

Recruiting

SCRI Oncology Partners /ID# 270162

Nashville, Tennessee, 37203

Recruiting

Texas Oncology - Dallas - Worth Street /ID# 278947

Dallas, Texas, 75246

Recruiting

Texas Oncology - Northeast Texas /ID# 272000

Tyler, Texas, 75702

Recruiting

Community Cancer Trials Of Utah /ID# 276598

Ogden, Utah, 84405

Recruiting

Virginia Cancer Specialists - Fairfax /ID# 272004

Fairfax, Virginia, 22031

Recruiting

Medical Oncology Associates - Spokane /ID# 277172

Spokane, Washington, 99208

Recruiting

Northwest Medical Specialties Tacoma /ID# 270534

Tacoma, Washington, 98405

Recruiting