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.
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).
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
Sequential
Standard of Care
DrugStandard of Care
Telisotuzumab Adizutecan
DrugIntravenous (IV)
Osimertinib (Osi)
DrugOral
Cisplatin
DrugIV
Carboplatin
DrugIV
Pemetrexed
DrugIV
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Treatment groupsSee each treatment group below.
Stage 1: Objective Response (OR) Based on Blinded Independent Central Review (BICR) Assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
OR is defined as confirmed complete response (CR) or confirmed partial response (PR) per BICR based on RECIST version 1.1.
Stage 2: Progression-free survival (PFS) based on BICR assessment per RECIST version 1.1.
PFS is defined as the time from the participant's randomization date to the first occurrence of radiographic progression per BICR based on RECIST version 1.1 or death from any cause, whichever occurs earlier.
Number of Participants with Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Stage 1: PFS based on BICR assessment per RECIST version 1.1.
PFS is defined as the time from the participant's randomization date to the first occurrence of radiographic progression per BICR based on RECIST version 1.1 or death from any cause, whichever occurs earlier.
Stage 1: Duration of response (DoR) based on BICR assessment per RECIST version 1.1.
DOR is defined as the time from the first documented CR or PR per BICR to the first occurrence of radiographic progression per RECIST version 1.1 or death from any cause, whichever occurs first. DOR is defined for participants with confirmed CR/PR.
Stage 1: Disease control rate (DC) based on BICR assessment per RECIST version 1.1.
DC is defined as best overall response of confirmed CR or confirmed PR, or stable disease (SD) for at least 12 weeks following randomization date based on RECIST version 1.1, as determined by the BICR.
Stage 1: Overall Survival
OS is defined as the time from participant's randomization date to the event of death from any cause.
