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NCT07005102PHASE2, PHASE3Recruiting

A Study to Assess Adverse Events, Change in Disease Activity of Intravenous Telisotuzumab Adizutecan in Combination With Osimertinib as First-Line Treatment in Adult Participants With Locally Advanced Unresectable or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer

AbbVie

Start Date

8/3/2025

Completion Date

11/1/2036

Summary

Non-small cell lung cancer (NSCLC) is a common type of lung cancer where abnormal cells in the lungs grow out of control. The purpose of this study is to assess adverse events and change in disease activity "when telisotuzumab adizutecan is given in combination with a fixed dose of osimertinib (Osi)or standard of care (Osi plus platinum/pemetrexed chemotherapy). Telisotuzumab adizutecan is an investigational drug being developed for the treatment of NSCLC. Osi is a drug approved for the treatment of NSCLC. This study will be divided into two stages, in the first stage participants will receive increasing doses of telisotuzumab adizutecan with Osi. Participants will then be randomized into 4 groups called treatment arms where 3 groups will receive 1 of 3 doses of telisotuzumab adizutecan from from the dose escalation phase with Osi, or standard of care (Osi plus chemotherapy). In the second stage participants will receive the optimal dose of telisotuzumab adizutecan, from the previous stage, with Osi, or SOC. Approximately 854 adult participants with 1L estimated glomerular filtration rate (EGFR) mut (mutated) not sufficient quantity (NSq) NSCLC will be enrolled in the study in 200 sites worldwide. In Stage 1, during dose escalation participants will receive increasing intravenous (IV) doses of telisotuzumab adizutecan with oral Osi tablets. participants will receive 1 of 3 doses of telisotuzumab adizutecan with Osi, or standard of care (Osi plus chemotherapy). In stage 2 participants will receive the optimal dose of IV telisotuzumab adizutecanin with oral Osi tablet, or SOC. The study will run for a duration of approximately 76 months. 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 an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 during the screening period and prior to dosing of study treatment on Cycle 1 Day 1. * Must consent to provide recently obtained formalin-fixed, paraffin-embedded (FFPE) tumor tissue (ideally collected during or after locally advanced or metastatic diagnosis) or archived tissue during screening for c-Met immunohistochemistry (IHC) testing and study stratification. c-Met IHC results are required prior to randomization. * Must have at least one non-irradiated measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. If only one measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and as long as it has not been biopsied within 14 days of the baseline tumor assessment scans. * Any toxicities from prior systemic anti-cancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) Grade 1 or baseline level (except for alopecia \[any grade\] or Grade \<= 2 peripheral neuropathy). * Should not have any major, life-threatening conditions and life expectancy as determined by the investigator should be at least 3 months. * No prior estimated glomerular filtration rate (EGFR) tyrosine kinase inhibitor (TKI) in the locally advanced and/or metastatic setting (except for when it is allowed on study prior to C1D1). Participants treated with prior EGFR TKI in the adjuvant setting are allowed to enroll provided that \>= 126 months (since last dose of e.g., adjuvant osimertinib) have passed before Cycle 1, Day 1. * Diagnosis of histologically or cytologically confirmed metastatic/locally advanced non-squamous NSCLC with documented classical EGFR mutation (Exon 19 Del or Exon 21 L858R) either alone or in combination with other EGFR mutations as detected by an Food and Drug Administration (FDA)-approved or other validated test in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (sites in the US) or an accredited Laboratory (sites outside of the US) in accordance with site standard of care. A copy of the test report documenting the EGFR mutation must be available in the participant records. Exclusion Criteria: * History of interstitial lung disease (ILD), pneumonitis that required treatment with systemic steroids, or any evidence of active ILD/pneumonitis on screening chest computed tomography (CT) scan. * History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis. * Participants has leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation. * History of any malignancy other than disease under study except for 1. Malignancy treated with curative intent and with no known active disease present for 2 years before the first dose of study treatment and felt to be at low risk for recurrence by investigator. 2. Successfully treated nonmelanoma skin cancer. 3. Localized carcinoma in situ of the cervix. 4. Breast Cancer; lobular carcinoma in situ or ductal carcinoma in situ that is considered completely cured.

Interventions

DRUG

Standard of Care

DRUG

Telisotuzumab Adizutecan

DRUG

Osimertinib (Osi)

DRUG

Cisplatin

DRUG

Carboplatin

DRUG

Pemetrexed

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Conditions

Non-Squamous Non-Small Cell Lung Cancer

Locations

Ironwood Cancer and Research Centers - Chandler II /ID# 275443

Chandler, Arizona 85224

United States

USC Norris Comprehensive Cancer Center /ID# 275343

Los Angeles, California 90033

United States

Usc Norris Oncology/Hematology Treatment Center /ID# 278673

Newport Beach, California 92663

United States

University Colorado Cancer Center /ID# 275382

Aurora, Colorado 80045-2517

United States

Mid Florida Hematology And Oncology Center /ID# 275278

Orange City, Florida 32763

United States

Kaiser Permanente Moanalua Medical Center /ID# 275942

Honolulu, Hawaii 96819

United States

The Iowa Clinic /ID# 276020

West Des Moines, Iowa 50266

United States

Nho - Revive Research Institute /ID# 276115

Lincoln, Nebraska 68506

United States

Renown Regional Medical Center /ID# 276049

Reno, Nevada 89502

United States

Texas Oncology - South Austin /ID# 276033

Austin, Texas 78745

United States

The University of Texas MD Anderson Cancer Center /ID# 275107

Houston, Texas 77030

United States

Texas Oncology - Palestine Cancer Center /ID# 276034

Palestine, Texas 75801

United States

Virginia Cancer Specialists - Fairfax /ID# 275071

Fairfax, Virginia 22031

United States

University of Washington Medical Center /ID# 275866

Seattle, Washington 98195

United States

Liverpool Hospital /ID# 276304

Liverpool, New South Wales 2170

Australia

The Queen Elizabeth Hospital /ID# 275719

Woodville, South Australia 5011

Australia

Austin Health /ID# 275505

Heidelberg, Victoria 3084

Australia

St John Of God Murdoch Hospital /ID# 275700

Murdoch, Western Australia 6150

Australia

Jessa Ziekenhuis - Campus Virga Jesse /ID# 275585

Hasselt, Limburg 3500

Belgium

Universitair Ziekenhuis Leuven /ID# 275586

Leuven, Vlaams-Brabant 3000

Belgium

AZ-Delta. /ID# 275753

Roeselare, West-Vlaanderen 8800

Belgium

CHU de Liege /ID# 277971

Liège, 4000

Belgium

The Ottawa Hospital - General Campus /ID# 275611

Ottawa, Ontario K1H 8L6

Canada

Princess Margaret Cancer Centre /ID# 274845

Toronto, Ontario M5G 2M9

Canada

Union Hospital Tongji Medical College /ID# 278711

Wuhan, Hubei 430048

China

Rabin Medical Center. /ID# 274540

Petah Tikva, Central District 4941492

Israel

The Chaim Sheba Medical Center /ID# 274541

Ramat Gan, Tel Aviv 5265601

Israel

Rambam Health Care Campus- Haifa /ID# 274542

Haifa, 3109601

Israel

IRCCS Istituti Fisioterapici Ospitalieri-Istituto Nazionale Tumori Regina Elena /ID# 274948

Rome, Roma 00144

Italy

Azienda Ospedaliero Universitaria San Luigi Gonzaga /ID# 275215

Orbassano, Torino 10043

Italy

Yokohama Municipal Citizen's Hospital /ID# 275682

Yokohama, Kanagawa 221-0855

Japan

Niigata University Medical and Dental Hospital /ID# 275685

Niigata, Niigata 951-8520

Japan

Osaka Medical And Pharmaceutical University Hospital /ID# 275684

Takatsuki, Osaka 569-8686

Japan

Shizuoka Cancer Center /ID# 278082

Sunto-gun, Shizuoka 411-8777

Japan

Juntendo University Hospital /ID# 276424

Bunkyo-ku, Tokyo 113-8431

Japan

National Cancer Center Hospital /ID# 275678

Chuo-Ku, Tokyo 104-0045

Japan

Unidade Local de Saude de Braga, EPE /ID# 275394

Braga, 4710-243

Portugal

Unidade Local de Saude de Santo Antonio /ID# 275387

Porto, 4099-003

Portugal

Hospital Cuf Porto /ID# 275395

Porto, 4100-180

Portugal

National Cancer Centre Singapore /ID# 275986

Singapore, Central Singapore 169611

Singapore

National University Hospital /ID# 275988

Singapore, 119074

Singapore

Inje University Haeundae Paik Hospital /ID# 275388

Busan, Busan Gwang Yeogsi 48108

South Korea

Chungbuk National University Hospital /ID# 275768

Cheongju-si, North Chungcheong 28644

South Korea

Yonsei University Health System Severance Hospital /ID# 275384

Seoul, Seoul Teugbyeolsi 03722

South Korea

Asan Medical Center /ID# 275600

Seoul, Seoul Teugbyeolsi 05505

South Korea

Samsung Medical Center /ID# 278083

Seoul, Seoul Teugbyeolsi 06351

South Korea

Hospital Clinic de Barcelona /ID# 275476

Barcelona, 08036

Spain

Hospital General Universitario Gregorio Maranon /ID# 275475

Madrid, 28007

Spain

Hospital Universitario 12 de Octubre /ID# 277698

Madrid, 28041

Spain

Instituto Valenciano de Oncología /ID# 275471

Valencia, 46009

Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 275293

Kaohsiung City, 807

Taiwan

National Taiwan University Cancer Center (Ntucc) /ID# 275291

Taipei, 106

Taiwan

Taipei Veterans General Hospital /ID# 275292

Taipei, 112

Taiwan