A Phase 3, Open-Label, Randomized Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 776
- 试验地点
- 250
- 主要终点
- Main Study: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
The purpose of this study is to assess the efficacy of adding lazertinib to amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing strategies) and amivantamab, carboplatin and pemetrexed (ACP) compared with carboplatin and pemetrexed (CP) in participants with locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure. The purpose of the extension cohort is to further describe the safety and efficacy for the ACP-L dosing schedule versus ACP with additional data. After completion of the primary analysis, the study may eventually transition to an open-label extension (OLE) or long-term extension (LTE) phase during which participants will have the option to continue their assigned treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Participant must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, that has not been previously irradiated
- •Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC), characterized at or after the time of locally advanced or metastatic disease diagnosis by either epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R mutation
- •A participant with a history of brain metastases must have had all lesions treated as clinically indicated (that is, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization and the participant can be receiving no greater than10 milligrams (mg) prednisone or equivalent daily for the treatment of intracranial disease
- •Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
- •Any toxicities from prior systemic anticancer therapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade <= 2 peripheral neuropathy, or Grade <= 2 hypothyroidism stable on hormone replacement)
- •A participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
- •Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first-line treatment for locally advanced or metastatic disease or in the second- line setting after prior treatment with first- or second-generation EGFR tyrosine kinase inhibitor (TKI) as a monotherapy. Participants who received either neoadjuvant and/or adjuvant treatment of any type are eligible if progression to locally advanced or metastatic disease occurred at least 12 months after the last dose of such therapy and then the participant progressed on or after osimertinib in the locally advanced or metastatic setting. Treatment with osimertinib must be discontinued at least 8 days (4 half-lives) prior to randomization (that is last dose no later than Day -8)
排除标准
- •Participant received radiotherapy for palliative treatment of NSCLC less than 14 days prior to randomization
- •Participant with symptomatic or progressive brain metastases
- •Participant has history of or current evidence of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation
- •Participant has known small cell transformation
- •Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
- •Participant has a history of clinically significant cardiovascular disease including, but not limited to diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to randomization; myocardial infarction; unstable angina; stroke; transient ischemic attack; coronary/peripheral artery bypass graft; or acute coronary syndrome. Participant has a significant genetic predisposition to venous thromboembolic events. Participant has a prior history of venous thromboembolic events and is not on appropriate therapeutic anticoagulation as per National Comprehensive Cancer Network or local guidelines
研究组 & 干预措施
Arm A: LACP/ACP-L
LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.
干预措施: Carboplatin (Drug)
Arm A2 (Extension Cohort): ACP-L
Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.
干预措施: Lazertinib (Drug)
Arm A: LACP/ACP-L
LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.
干预措施: Amivantamab (Drug)
Arm A: LACP/ACP-L
LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.
干预措施: Lazertinib (Drug)
Arm A: LACP/ACP-L
LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.
干预措施: Pemetrexed (Drug)
Arm B: CP (Carboplatin and Pemetrexed)
Participants will receive Pemetrexed in combination with Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Pemetrexed as maintenance until disease progression.
干预措施: Pemetrexed (Drug)
Arm B: CP (Carboplatin and Pemetrexed)
Participants will receive Pemetrexed in combination with Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Pemetrexed as maintenance until disease progression.
干预措施: Carboplatin (Drug)
Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed)
Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
干预措施: Amivantamab (Drug)
Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed)
Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
干预措施: Pemetrexed (Drug)
Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed)
Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
干预措施: Carboplatin (Drug)
Arm A2 (Extension Cohort): ACP-L
Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.
干预措施: Amivantamab (Drug)
Arm A2 (Extension Cohort): ACP-L
Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.
干预措施: Pemetrexed (Drug)
Arm A2 (Extension Cohort): ACP-L
Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.
干预措施: Carboplatin (Drug)
Arm C2 (Extension Cohort): ACP
Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
干预措施: Pemetrexed (Drug)
Arm C2 (Extension Cohort): ACP
Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
干预措施: Amivantamab (Drug)
Arm C2 (Extension Cohort): ACP
Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Main Study: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)
时间窗: From randomization to either disease progression or death, whichever occurred first (up to 1 year 7 months)
PFS is defined as the time from randomization until the date of objective disease progression or death, whichever came first, as assessed by BICR according to RECIST version 1.1. Progressed disease: Sum of diameters increased by greater than or equal to (\>=)20 percent (%) and \>=5 millimeter (mm) from nadir (including baseline if it was smallest sum).
Main Study + Extension Cohort: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
时间窗: up to 4 years 10 months
Follow-up for the extension cohort is still ongoing and thus results from the analysis that includes the extension cohort will be reported up on study completion.
Main Study + Extension Cohort: Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review
时间窗: Up to 4 years 10 months
次要结局
- Main Study+ Extension Cohort: Number of Participants With Adverse Events (AEs) by Severity(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Serum Concentration of Amivantamab(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Overall Survival(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Objective Response Rate as Assessed by Blinded Independent Central Review(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Duration of Response as Assessed by Blinded Independent Central Review(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Time to Subsequent Therapy(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Progression-free Survival (PFS) After First Subsequent Therapy (PFS2)(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Time to Symptomatic Progression(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Intracranial Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review(Up to 4 years 10 months)
- Main Study: Number of Participants With Adverse Events (AEs)(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Number of Participants With Clinical Laboratory Abnormalities(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Plasma Concentration of Lazertinib(Up to 4 years 10 months)
- Main Study + Extension Cohort: Number of Participants With Serum Anti-amivantamab Antibodies(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Change From Baseline With Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ)(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Change From Baseline With European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)(Up to 4 years 10 months)
- Main Study+ Extension Cohort: Change From Baseline With Patient-Reported Outcomes Measurement Information System -Physical Function (PROMIS-PF)(Up to 4 years 10 months)
研究者
研究点 (250)
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