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
- 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.
- Short title
- 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
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Recruiting
- Phase
- Phase 2/Phase 3
- Study type
- Interventional
- Completion date
- 2036-11-01
- First posted
- 2025-06-05
- Registry last updated
- 2026-06-08
- Primary completion date
- 2031-12-01
- Start date
- 2025-08-03
- Participants
- Participant count basis
- Estimated
- Planned participants
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- AbbVie
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT07005102
- ClinicalTrials.gov ID
- NCT07005102
- Registry record
- Open registry record
- Allocation
- Randomised
- Model
- Sequential
- Purpose
- Treatment
- Masking
- Quadruple masking
- Masked roles
- Participants, Care providers, Investigators, Outcome assessors
Stage 1: 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
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.
Timeframe: Up to Approximately 76 Months
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)
Timeframe: Up to Approximately 76 Months
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.
Timeframe: Up to Approximately 76 Months
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.
Timeframe: Up to Approximately 76 Months
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.
Timeframe: Up to Approximately 76 Months
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
Timeframe: Up to Approximately 76 Months
OS is defined as the time from participant's randomization date to the event of death from any cause.
Stage 2: Overall Survival
Timeframe: Up to Approximately 76 Months
OS is defined as the time from participant's randomization date to the event of death from any cause.
Stage 2: OR based on BICR assessment per RECIST version 1.1.
Timeframe: Up to Approximately 76 Months
OR is defined as confirmed CR or confirmed PR per BICR based on RECIST version 1.1.
Stage 2: DoR based on BICR assessment per RECIST version 1.1.
Timeframe: Up to Approximately 76 Months
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 2: DC based on BICR assessment per RECIST version 1.1.
Timeframe: Up to Approximately 76 Months
DC is defined as best overall response of confirmed CR or confirmed PR, or SD for at least 12 weeks following randomization date based on RECIST version 1.1, as determined by the BICR.
Stage 2: 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
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).
Stage 2: 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
The EORTC QLQ-LC13 is a lung cancer specific module and consists of 13 questions assessing lung cancer-associated symptoms and treatment-related effects, including one multiple-item scale to assess dyspnea and a series of single items assessing coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain, and pain medication. Each item is assessed on a Likert scale from 1 (not at all) to 4 (very much).
Stage 2: Change from baseline at Week 12 in GHS/QoL as measured by the EORTC QLQ-C30.
Timeframe: Up to Approximately 76 Months
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Healthy volunteers
- No
- 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.
-
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
- 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.
- Localized carcinoma in situ of the cervix.
- Breast Cancer; lobular carcinoma in situ or ductal carcinoma in situ that is considered completely cured.
- Ironwood Cancer and Research Centers - Chandler II /ID# 275443Chandler, United StatesRecruiting
- USC Norris Comprehensive Cancer Center /ID# 275343Los Angeles, United StatesRecruiting
- Usc Norris Oncology/Hematology Treatment Center /ID# 278673Newport Beach, United StatesRecruiting
- University Colorado Cancer Center /ID# 275382Aurora, United StatesRecruiting
- Mid Florida Hematology And Oncology Center /ID# 275278Orange City, United StatesRecruiting
- Kaiser Permanente Moanalua Medical Center /ID# 275942Honolulu, United StatesRecruiting
- The Iowa Clinic /ID# 276020West Des Moines, United StatesCompleted
- Nho - Revive Research Institute /ID# 276115Lincoln, United StatesRecruiting
- Renown Regional Medical Center /ID# 276049Reno, United StatesRecruiting
- Texas Oncology - South Austin /ID# 276033Austin, United StatesRecruiting
- The University of Texas MD Anderson Cancer Center /ID# 275107Houston, United StatesRecruiting
- Texas Oncology - Palestine Cancer Center /ID# 276034Palestine, United StatesRecruiting
- Virginia Cancer Specialists - Fairfax /ID# 275071Fairfax, United StatesRecruiting
- University of Washington Medical Center /ID# 275866Seattle, United StatesRecruiting
- Liverpool Hospital /ID# 276304Liverpool, AustraliaRecruiting
- The Queen Elizabeth Hospital /ID# 275719Woodville, AustraliaRecruiting
- Austin Health /ID# 275505Heidelberg, AustraliaRecruiting
- St John Of God Murdoch Hospital /ID# 275700Murdoch, AustraliaRecruiting
- Jessa Ziekenhuis - Campus Virga Jesse /ID# 275585Hasselt, BelgiumRecruiting
- Universitair Ziekenhuis Leuven /ID# 275586Leuven, BelgiumRecruiting
- AZ-Delta. /ID# 275753Roeselare, BelgiumRecruiting
- CHU de Liege /ID# 277971Liège, BelgiumRecruiting
- The Ottawa Hospital - General Campus /ID# 275611Ottawa, CanadaRecruiting
- Princess Margaret Cancer Centre /ID# 274845Toronto, CanadaCompleted
- Union Hospital Tongji Medical College /ID# 278711Wuhan, ChinaRecruiting
And 28 more, listed on the interactive page.
Other registry identifiers
- 2024-518586-10