Clinical trial NCT07005102: 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
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Non-Squamous Non-Small Cell Lung Cancer
Keywords: Non-Squamous Non-Small Cell Lung Cancer
Telisotuzumab Adizutecan
Osimertinib
ABBV-400, Stand of Care
Cancer
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2025-06-05
Enrollment: 694
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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), 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.


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.

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.

Primary outcomes:
measure: Phase 2: Objective Response (OR) Based on Blinded Independent Central Review (BICR) Assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
timeFrame: Up to Approximately 76 Months
measure: Phase 3: Progression-free survival (PFS) based on BICR assessment per RECIST version 1.1.
timeFrame: Up to Approximately 76 Months
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to Approximately 76 Months
Secondary outcomes:
measure: Phase 2: PFS based on BICR assessment per RECIST version 1.1.
timeFrame: Up to Approximately 76 Months
measure: Phase 2: Duration of response (DoR) based on BICR assessment per RECIST version 1.1.
timeFrame: Up to Approximately 76 Months
measure: Phase 2: Disease control rate (DC) based on BICR assessment per RECIST version 1.1.
timeFrame: Up to Approximately 76 Months
measure: Phase 2: Overall Survival
timeFrame: Up to Approximately 76 Months
measure: Phase 3: Overall Survival
timeFrame: Up to Approximately 76 Months
measure: Phase 3: OR based on BICR assessment per RECIST version 1.1.
timeFrame: Up to Approximately 76 Months
measure: Phase 3: DoR based on BICR assessment per RECIST version 1.1.
timeFrame: Up to Approximately 76 Months
measure: Phase 3: DC based on BICR assessment per RECIST version 1.1.
timeFrame: Up to Approximately 76 Months
measure: Phase 3: Change from baseline at Week 12 in physical functioning as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).
timeFrame: Up to Approximately 76 Months
measure: Phase 3: Change from baseline at Week 12 in key lung cancer symptoms as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC QLQ-LC13)
timeFrame: Up to Approximately 76 Months
measure: Phase 3: Change from baseline at Week 12 in GHS/QoL as measured by the EORTC QLQ-C30.
timeFrame: Up to Approximately 76 Months
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: