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

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Non-Squamous Non-Small Cell Lung Cancer

Treatments: Drug: Osimertinib (Osi); Drug: Telisotuzumab Adizutecan; Drug: Standard of Care

Study type: Interventional

Funder types: Industry

Identifiers

NCT07005102

M25-287

2024-518586-10 (Other Identifier)

Details and patient eligibility

About

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), Osi alone, or standard of care (SOC) alone.

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 optimized doses of telisotuzumab adizutecan from the dose escalation phase with Osi, or Osi alone. In the second stage participants will receive the optimal dose of telisotuzumab adizutecan, from the previous stage, with Osi, or SOC. Approximately 694 adult participants with mCRC 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. During dose optimization participants will receive OSi alone or with 1 of 3 optimized doses of telisotuzumab adizutecan. In stage 2 participnats will recieve 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.

Enrollment: 694 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

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 subject has spinal cord compression not definitively treated with surgery or radiation.
• History of any malignancy except for 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, successfully treated nonmelanoma skin cancer or localized carcinoma in situ of the cervix.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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694 participants in 7 patient groups

Stage 1: Escalation Telisotuzumab Adizutecan with Osimertinib

Experimental group

Description:

Participants will receive increasing doses of telisotuzumab adizutecan with osimertinib (Osi), as part of the approximately 76 month study duration.

Treatment:

Drug: Telisotuzumab Adizutecan

Drug: Osimertinib (Osi)

Stage 1: Expansion Telisotuzumab Adizutecan Dose A with Osi

Experimental group

Description:

Participants will receive telisotuzumab adizutecan dose A with Osi, as part of the approximately 76 month study duration.

Treatment:

Drug: Telisotuzumab Adizutecan

Drug: Osimertinib (Osi)

Stage 1: Expansion Telisotuzumab Adizutecan Dose B with Osi

Experimental group

Description:

Participants will receive telisotuzumab adizutecan dose B with Osi, as part of the approximately 76 month study duration.

Treatment:

Drug: Telisotuzumab Adizutecan

Drug: Osimertinib (Osi)

Stage 1: Expansion Telisotuzumab Adizutecan Dose C with Osi

Experimental group

Description:

Participants will receive telisotuzumab adizutecan dose C with Osi, as part of the approximately 76 month study duration.

Treatment:

Drug: Telisotuzumab Adizutecan

Drug: Osimertinib (Osi)

Stage 1: Expansion Osi

Experimental group

Description:

Participants will receive Osi, as part of the approximately 76 month study duration.

Treatment:

Drug: Osimertinib (Osi)

Stage 2: Standared of Care (SOC) Osi

Experimental group

Description:

Participants will receive Osi, as part of the approximately 76 month study duration.

Treatment:

Drug: Standard of Care

Stage 2: Telisotuzumab Adizutecan Optimized with Osi

Experimental group

Description:

Participants will receive the optimized dose of telisotuzumab adizutecan with Osi, as part of the approximately 76 month study duration.

Treatment:

Drug: Telisotuzumab Adizutecan

Drug: Osimertinib (Osi)