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

Official 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

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: SEQUENTIAL
• Masking: QUADRUPLE
• Enrollment: 854 participants

Study Arms

• Stage 1: Escalation Telisotuzumab Adizutecan + Osimertinib (EXPERIMENTAL)
  Participants will receive increasing doses of telisotuzumab adizutecan with osimertinib (Osi), as part of the approximately 76 month study duration.
• Stage 1: Expansion Telisotuzumab Adizutecan Dose A + Osi (EXPERIMENTAL)
  Participants will receive telisotuzumab adizutecan dose A with Osi, as part of the approximately 76 month study duration.
• Stage 1: Expansion Telisotuzumab Adizutecan Dose B + Osi (EXPERIMENTAL)
  Participants will receive telisotuzumab adizutecan dose B with Osi, as part of the approximately 76 month study duration.
• Stage 1: Expansion Telisotuzumab Adizutecan Dose C + Osi (EXPERIMENTAL)
  Participants will receive telisotuzumab adizutecan dose C with Osi, as part of the approximately 76 month study duration.
• Stage 1: Expansion Osi + Chemotherapy + Pemetrexed (EXPERIMENTAL)
  Participants will receive Osi with chemotherapy followed by Osi with pemetrexed, as part of the approximately 76 month study duration.
• Stage 2: Standared of Care (SOC) (EXPERIMENTAL)
  Participants will receive SOC, as part of the approximately 76 month study duration.
• Stage 2: Optimized Telisotuzumab Adizutecan + Osi (EXPERIMENTAL)
  Participants will receive the optimized dose of telisotuzumab adizutecan with Osi, as part of the approximately 76 month study duration.

Interventions

• DRUG: Standard of Care — Standard of Care
• DRUG: Telisotuzumab Adizutecan — Intravenous (IV)
• DRUG: Osimertinib (Osi) — Oral
• DRUG: Cisplatin — IV
• DRUG: Carboplatin — IV

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)

Secondary Outcomes

• Stage 1: PFS based on BICR assessment per RECIST version 1.1. (Up to Approximately 76 Months)
• Stage 1: Duration of response (DoR) based on BICR assessment per RECIST version 1.1. (Up to Approximately 76 Months)
• Stage 1: Disease control rate (DC) based on BICR assessment per RECIST version 1.1. (Up to Approximately 76 Months)
• Stage 1: Overall Survival (Up to Approximately 76 Months)
• Stage 2: Overall Survival (Up to Approximately 76 Months)

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.

Trial Locations

• Ironwood Cancer & Research Centers - Chandler II /ID# 275443, Chandler, Arizona, United States
• USC Norris Comprehensive Cancer Center /ID# 275343, Los Angeles, California, United States
• Usc Norris Oncology/Hematology Treatment Center /ID# 278673, Newport Beach, California, United States
• University Colorado Cancer Center /ID# 275382, Aurora, Colorado, United States
• Mid Florida Hematology And Oncology Center /ID# 275278, Orange City, Florida, United States
• The Iowa Clinic /ID# 276020, West Des Moines, Iowa, United States
• Nho - Revive Research Institute /ID# 276115, Lincoln, Nebraska, United States
• Renown Regional Medical Center /ID# 276049, Reno, Nevada, United States
• Texas Oncology - South Austin /ID# 276033, Austin, Texas, United States
• The University of Texas MD Anderson Cancer Center /ID# 275107, Houston, Texas, United States
• ...and 10 more locations

Contact Information

• ABBVIE CALL CENTER — CONTACT
  Phone: 844-663-3742
  Email: abbvieclinicaltrials@abbvie.com

Study Officials

• ABBVIE INC. — STUDY_DIRECTOR
  AbbVie

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