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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
NCT07005102 · AbbVie
In plain English
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Official title
A Phase 2/3 Randomized Study to Evaluate the Safety, Efficacy, and Optimal Dose of Telisotuzumab Adizutecan in Combination With Osimertinib as First-Line Treatment in Patients With Locally Advanced Unresectable or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer
About this study
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
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.
Study design
Enrollment target: 854 participants
Allocation: randomized
Masking: quadruple
Age groups: adult, older_adult
Timeline
Starts: 2025-08-03
Estimated completion: 2036-11
Last updated: 2026-06-08
Interventions
Drug: Standard of CareDrug: Telisotuzumab AdizutecanDrug: Osimertinib (Osi)Drug: CisplatinDrug: CarboplatinDrug: Pemetrexed
Primary outcomes
- • Stage 1: Objective Response (OR) Based on Blinded Independent Central Review (BICR) Assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Up to Approximately 76 Months)
- • Stage 2: Progression-free survival (PFS) based on BICR assessment per RECIST version 1.1. (Up to Approximately 76 Months)
- • Number of Participants with Adverse Events (AEs) (Up to Approximately 76 Months)
Sponsor
AbbVie · industry
Contacts & investigators
ContactABBVIE CALL CENTER · contact · abbvieclinicaltrials@abbvie.com · 844-663-3742
InvestigatorABBVIE INC. · study_director, AbbVie
All locations (53)
Ironwood Cancer and Research Centers - Chandler II /ID# 275443Recruiting
Chandler, Arizona, United States
USC Norris Comprehensive Cancer Center /ID# 275343Recruiting
Los Angeles, California, United States
Usc Norris Oncology/Hematology Treatment Center /ID# 278673Recruiting
Newport Beach, California, United States
University Colorado Cancer Center /ID# 275382Recruiting
Aurora, Colorado, United States
Mid Florida Hematology And Oncology Center /ID# 275278Recruiting
Orange City, Florida, United States
Kaiser Permanente Moanalua Medical Center /ID# 275942Recruiting
Honolulu, Hawaii, United States
The Iowa Clinic /ID# 276020Completed
West Des Moines, Iowa, United States
Nho - Revive Research Institute /ID# 276115Recruiting
Lincoln, Nebraska, United States
Renown Regional Medical Center /ID# 276049Recruiting
Reno, Nevada, United States
Texas Oncology - South Austin /ID# 276033Recruiting
Austin, Texas, United States
The University of Texas MD Anderson Cancer Center /ID# 275107Recruiting
Houston, Texas, United States
Texas Oncology - Palestine Cancer Center /ID# 276034Recruiting
Palestine, Texas, United States
Virginia Cancer Specialists - Fairfax /ID# 275071Recruiting
Fairfax, Virginia, United States
University of Washington Medical Center /ID# 275866Recruiting
Seattle, Washington, United States
Liverpool Hospital /ID# 276304Recruiting
Liverpool, New South Wales, Australia
The Queen Elizabeth Hospital /ID# 275719Recruiting
Woodville, South Australia, Australia
Austin Health /ID# 275505Recruiting
Heidelberg, Victoria, Australia
St John Of God Murdoch Hospital /ID# 275700Recruiting
Murdoch, Western Australia, Australia
Jessa Ziekenhuis - Campus Virga Jesse /ID# 275585Recruiting
Hasselt, Limburg, Belgium
Universitair Ziekenhuis Leuven /ID# 275586Recruiting
Leuven, Vlaams-Brabant, Belgium
AZ-Delta. /ID# 275753Recruiting
Roeselare, West-Vlaanderen, Belgium
CHU de Liege /ID# 277971Recruiting
Liège, Belgium
The Ottawa Hospital - General Campus /ID# 275611Recruiting
Ottawa, Ontario, Canada
Princess Margaret Cancer Centre /ID# 274845Completed
Toronto, Ontario, Canada
Union Hospital Tongji Medical College /ID# 278711Recruiting
Wuhan, Hubei, China
Rabin Medical Center. /ID# 274540Recruiting
Petah Tikva, Central District, Israel
The Chaim Sheba Medical Center /ID# 274541Recruiting
Ramat Gan, Tel Aviv, Israel
Rambam Health Care Campus- Haifa /ID# 274542Recruiting
Haifa, Israel
IRCCS Istituti Fisioterapici Ospitalieri-Istituto Nazionale Tumori Regina Elena /ID# 274948Recruiting
Rome, Roma, Italy
Azienda Ospedaliero Universitaria San Luigi Gonzaga /ID# 275215Recruiting
Orbassano, Torino, Italy
Yokohama Municipal Citizen's Hospital /ID# 275682Recruiting
Yokohama, Kanagawa, Japan
Niigata University Medical and Dental Hospital /ID# 275685Recruiting
Niigata, Niigata, Japan
Osaka Medical And Pharmaceutical University Hospital /ID# 275684Recruiting
Takatsuki, Osaka, Japan
Shizuoka Cancer Center /ID# 278082Recruiting
Sunto-gun, Shizuoka, Japan
Juntendo University Hospital /ID# 276424Recruiting
Bunkyo-ku, Tokyo, Japan
National Cancer Center Hospital /ID# 275678Recruiting
Chuo-Ku, Tokyo, Japan
Unidade Local de Saude de Braga, EPE /ID# 275394Recruiting
Braga, Portugal
Unidade Local de Saude de Santo Antonio /ID# 275387Recruiting
Porto, Portugal
Hospital Cuf Porto /ID# 275395Recruiting
Porto, Portugal
National Cancer Centre Singapore /ID# 275986Recruiting
Singapore, Central Singapore, Singapore
National University Hospital /ID# 275988Recruiting
Singapore, Singapore
Inje University Haeundae Paik Hospital /ID# 275388Recruiting
Busan, Busan Gwang Yeogsi, South Korea
Chungbuk National University Hospital /ID# 275768Recruiting
Cheongju-si, North Chungcheong, South Korea
Yonsei University Health System Severance Hospital /ID# 275384Recruiting
Seoul, Seoul Teugbyeolsi, South Korea
Asan Medical Center /ID# 275600Recruiting
Seoul, Seoul Teugbyeolsi, South Korea
Samsung Medical Center /ID# 278083Recruiting
Seoul, Seoul Teugbyeolsi, South Korea
Hospital Clinic de Barcelona /ID# 275476Recruiting
Barcelona, Spain
Hospital General Universitario Gregorio Maranon /ID# 275475Recruiting
Madrid, Spain
Hospital Universitario 12 de Octubre /ID# 277698Recruiting
Madrid, Spain
Instituto Valenciano de Oncología /ID# 275471Recruiting
Valencia, Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 275293Recruiting
Kaohsiung City, Taiwan
National Taiwan University Cancer Center (Ntucc) /ID# 275291Recruiting
Taipei, Taiwan
Taipei Veterans General Hospital /ID# 275292Recruiting
Taipei, Taiwan