A Randomized, Open-label Phase 3 Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Patients With EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
概览
- 阶段
- 3 期
- 干预措施
- Amivantamab
- 疾病 / 适应症
- Carcinoma, Non-Small-Cell Lung
- 发起方
- Janssen Research & Development, LLC
- 入组人数
- 308
- 试验地点
- 458
- 主要终点
- Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)
- 状态
- 进行中（未招募）
- 最后更新
- 19天前
概览
简要总结
The purpose of this study is to compare the efficacy, as demonstrated by progression-free survival (PFS), in participants treated with amivantamab in combination with chemotherapy, versus chemotherapy alone in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) characterized by EGFR Exon 20ins mutations.
研究者
入排标准
入选标准
- •Participant must have histologically or cytologically confirmed, locally advanced or metastatic, nonsquamous non-small cell lung cancer (NSCLC) with documented primary epidermal growth factor receptor (EGFR) Exon 20ins activating mutation
- •Participant must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Participant must agree to genetic characterization of tumor status through the required pretreatment tumor biopsy (or submission of equivalent archival material), as well as baseline and periodic blood samples for analysis of tumor mutations in the bloodstream
- •A female participant of childbearing potential must have a negative serum or urine 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
排除标准
- •Participant has evidence of synchronous NSCLC disease (as suggested by genetic characterization or radiographic appearance)
- •Participant has untreated brain metastases (a participant with definitively, locally treated metastases who is clinically stable, asymptomatic, and off corticosteroid treatment for at least 2 weeks prior to randomization is eligible)
- •Participant has history of spinal cord compression that has not been treated definitively with surgery or radiation
- •Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD, or radiation pneumonitis
- •Participant has a contraindication to the use of carboplatin or pemetrexed (refer to local prescribing information for each agent). Participant has a history of hypersensitivity to, or cannot take, vitamin B12 or folic acid
研究组 & 干预措施
Arm A: Amivantamab + Chemotherapy
Participants will receive pemetrexed 500 milligram per meter square (mg/m\^2) intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin area under the concentration-time curve 5 milligram per milliliter (mg/mL) per minute (AUC 5) will be administered as IV infusion on Day 1 of each 21 day cycle, for up to 4 cycles. Participants will receive amivantamab 1400 mg (1750 mg if body weight is \>=80 kilogram \[kg\]) by IV infusion once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is \>=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will continue to receive the amivantamab plus chemotherapy in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.
干预措施: Amivantamab
Arm B: Chemotherapy Alone
Participants will receive pemetrexed 500 mg/m\^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin AUC 5 IV infusion will be administered on Day 1 of each 21-day cycle for up to 4 cycles. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will either continue to receive the chemotherapy or cross over to amivantamab in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.
干预措施: Carboplatin
Arm A: Amivantamab + Chemotherapy
Participants will receive pemetrexed 500 milligram per meter square (mg/m\^2) intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin area under the concentration-time curve 5 milligram per milliliter (mg/mL) per minute (AUC 5) will be administered as IV infusion on Day 1 of each 21 day cycle, for up to 4 cycles. Participants will receive amivantamab 1400 mg (1750 mg if body weight is \>=80 kilogram \[kg\]) by IV infusion once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is \>=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will continue to receive the amivantamab plus chemotherapy in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.
干预措施: Carboplatin
Arm A: Amivantamab + Chemotherapy
Participants will receive pemetrexed 500 milligram per meter square (mg/m\^2) intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin area under the concentration-time curve 5 milligram per milliliter (mg/mL) per minute (AUC 5) will be administered as IV infusion on Day 1 of each 21 day cycle, for up to 4 cycles. Participants will receive amivantamab 1400 mg (1750 mg if body weight is \>=80 kilogram \[kg\]) by IV infusion once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is \>=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will continue to receive the amivantamab plus chemotherapy in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.
干预措施: Pemetrexed
Arm B: Chemotherapy Alone
Participants will receive pemetrexed 500 mg/m\^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin AUC 5 IV infusion will be administered on Day 1 of each 21-day cycle for up to 4 cycles. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will either continue to receive the chemotherapy or cross over to amivantamab in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.
干预措施: Pemetrexed
结局指标
主要结局
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 occurs first (up to 29 months)
PFS was defined as the time from randomization until the date of objective disease progression based on BICR using RECIST version 1.1 or death (by any cause) in the absence of progression, whichever came first. Participants who have not progressed or have not died at the time of analysis were censored at the time of the latest date of their last evaluable RECIST version 1.1 assessment. Pharmacodynamic: 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).
次要结局
- Overall Survival (OS)(Up to 5 years 3 months)
- Duration of Response (DoR)(Up to 5 years 3 months)
- Time to Symptomatic Progression (TTSP)(Up to 5 years 3 months)
- Objective Response Rate (ORR)(Up to 5 years 3 months)
- Number of Participants Treatment-emergent Adverse Events (TEAEs)(From Day 1 to 5 years 2 months)
- Serum Concentration of Amivantamab(Day 1 (Cycles 1, 2, 3, 5, 7, 9, 11, 13), Day 2 (Cycle 1))
- Progression-Free Survival After First Subsequent Therapy (PFS2)(Up to 5 years 3 months)
- Number of Participants With Clinical Laboratory Abnormalities(Up to 5 years 3 months)
- Number of Participants With Vital Signs Abnormalities(Up to 5 years 3 months)
- Time to Subsequent Therapy (TST)(Up to 5 years 3 months)
- Number of Participants TEAEs With Severity(From Day 1 to 5 years 2 months)
- Number of Participants With Anti-Amivantamab Antibodies(Day 1 (Cycles 1, 2, 3, 5, 7, 9, 11, 13), Day 2 (Cycle 1))
- Change From Baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)(From baseline to 5 years 3 months)
- Change From Baseline in Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF)(From baseline to 5 years 3 months)
- Number of Participants With Physical Examination Abnormalities(Up to 5 years 3 months)