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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 854
- 试验地点
- 92
- 主要终点
- Number of Participants with Adverse Events (AEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Stage 2: Standared of Care (SOC)
Participants will receive SOC, as part of the approximately 76 month study duration.
干预措施: Osimertinib (Osi) (Drug)
Stage 1: Escalation Telisotuzumab Adizutecan + Osimertinib
Participants will receive increasing doses of telisotuzumab adizutecan with osimertinib (Osi), as part of the approximately 76 month study duration.
干预措施: Osimertinib (Osi) (Drug)
Stage 2: Optimized Telisotuzumab Adizutecan + Osi
Participants will receive the optimized dose of telisotuzumab adizutecan with Osi, as part of the approximately 76 month study duration.
干预措施: Osimertinib (Osi) (Drug)
Stage 1: Expansion Telisotuzumab Adizutecan Dose A + Osi
Participants will receive telisotuzumab adizutecan dose A with Osi, as part of the approximately 76 month study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Stage 1: Expansion Telisotuzumab Adizutecan Dose B + Osi
Participants will receive telisotuzumab adizutecan dose B with Osi, as part of the approximately 76 month study duration.
干预措施: Osimertinib (Osi) (Drug)
Stage 1: Expansion Telisotuzumab Adizutecan Dose C + Osi
Participants will receive telisotuzumab adizutecan dose C with Osi, as part of the approximately 76 month study duration.
干预措施: Osimertinib (Osi) (Drug)
Stage 1: Expansion Osi + Chemotherapy + Pemetrexed
Participants will receive Osi with chemotherapy followed by Osi with pemetrexed, as part of the approximately 76 month study duration.
干预措施: Osimertinib (Osi) (Drug)
Stage 1: Expansion Osi + Chemotherapy + Pemetrexed
Participants will receive Osi with chemotherapy followed by Osi with pemetrexed, as part of the approximately 76 month study duration.
干预措施: Cisplatin (Drug)
Stage 1: Escalation Telisotuzumab Adizutecan + Osimertinib
Participants will receive increasing doses of telisotuzumab adizutecan with osimertinib (Osi), as part of the approximately 76 month study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Stage 1: Expansion Telisotuzumab Adizutecan Dose C + Osi
Participants will receive telisotuzumab adizutecan dose C with Osi, as part of the approximately 76 month study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Stage 1: Expansion Osi + Chemotherapy + Pemetrexed
Participants will receive Osi with chemotherapy followed by Osi with pemetrexed, as part of the approximately 76 month study duration.
干预措施: Carboplatin (Drug)
Stage 1: Expansion Osi + Chemotherapy + Pemetrexed
Participants will receive Osi with chemotherapy followed by Osi with pemetrexed, as part of the approximately 76 month study duration.
干预措施: Pemetrexed (Drug)
Stage 2: Standared of Care (SOC)
Participants will receive SOC, as part of the approximately 76 month study duration.
干预措施: Standard of Care (Drug)
Stage 1: Expansion Telisotuzumab Adizutecan Dose A + Osi
Participants will receive telisotuzumab adizutecan dose A with Osi, as part of the approximately 76 month study duration.
干预措施: Osimertinib (Osi) (Drug)
Stage 1: Expansion Telisotuzumab Adizutecan Dose B + Osi
Participants will receive telisotuzumab adizutecan dose B with Osi, as part of the approximately 76 month study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
Stage 2: Optimized Telisotuzumab Adizutecan + Osi
Participants will receive the optimized dose of telisotuzumab adizutecan with Osi, as part of the approximately 76 month study duration.
干预措施: Telisotuzumab Adizutecan (Drug)
结局指标
主要结局
Number of Participants with Adverse Events (AEs)
时间窗: 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: Objective Response (OR) Based on Blinded Independent Central Review (BICR) Assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
时间窗: 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.
时间窗: 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.
次要结局
- Stage 2: Overall Survival(Up to Approximately 76 Months)
- 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: OR based on BICR assessment per RECIST version 1.1.(Up to Approximately 76 Months)
- Stage 2: DoR based on BICR assessment per RECIST version 1.1.(Up to Approximately 76 Months)
- Stage 2: DC based on BICR assessment per RECIST version 1.1.(Up to Approximately 76 Months)
- 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).(Up to Approximately 76 Months)
- 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)(Up to Approximately 76 Months)
- Stage 2: Change from baseline at Week 12 in GHS/QoL as measured by the EORTC QLQ-C30.(Up to Approximately 76 Months)