A Phase 3, Open-label, Randomized Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Patients With EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer After Progression on Osimertinib and Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 418
- 试验地点
- 328
- 主要终点
- For All Regions Other Than the European Union (EU) and Others Accepting Cycle 2 Day 1: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State
研究概览
简要总结
The purpose of the study is to simplify amivantamab intravenous administration and to reduce dose times, by assessing a new formulation of amivantamab, amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), for subcutaneous administration. This formulation has the potential to enhance both the patient and physician experience with amivantamab by providing easier and accelerated administration.
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
- •Have histologically or cytologically confirmed, advanced or metastatic non-small cell lung cancer (NSCLC), characterized by either epidermal growth factor receptor (EGFR) Exon 19 deletion (Exon 19del) or Exon 21 leucine 858 to arginine substitution (Exon 21 L858R) mutation by an Food and Drug Administration (FDA)-approved or other validated test of either circulating tumor deoxyribonucleic acid (ctDNA) or tumor tissue in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United Started [US]) or an accredited local laboratory (sites outside of the US)
- •Have progressed on or after osimertinib (or another approved 3rd generation epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKI]) and platinum-based chemotherapy (irrespective of order). a) The 3rd generation EGFR TKI must have been administered as the first EGFR TKI for metastatic disease or as the second TKI after prior treatment with first- or second-generation EGFR TKI in participants with metastatic EGFR T790M mutation positive NSCLC. b) Participants who decline or are otherwise ineligible for chemotherapy may be enrolled after discussion with the medical monitor. c) Any adjuvant or neoadjuvant treatment, whether with a 3rd generation EGFR TKI or platinum based chemotherapy, would count towards the prior treatment requirement if the participant experienced disease
- •Have at least 1 measurable lesion, according to response evaluation criteria in solid tumors (RECIST) version 1.1
- •Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1
- •Any toxicities from prior anticancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade less than or equal to (<=) 2 peripheral neuropathy, and Grade <=2 hypothyroidism stable on hormone replacement)
排除标准
- •Participant has received cytotoxic, investigational, or targeted therapies beyond one regimen of platinum-based chemotherapy and EGFR inhibitors
- •Participant has received radiotherapy for palliative purposes less than 7 days prior to randomization
- •Participant has symptomatic or progressive brain metastases
- •Participant has leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation
- •Participant has uncontrolled tumor-related pain
- •Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
研究组 & 干预措施
Arm A: Lazertinib with Amivantamab SC-CF
Lazertinib 240 milligrams (mg) will be administered orally once daily. Participants will receive amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), 1600 mg/ 2240 mg depending on the body weight by manual injection. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the long-term extension (LTE) Phase.
干预措施: Amivantamab Subcutaneous and Co-Formulated with Recombinant Human Hyaluronidase (SC CF) (Drug)
Arm B: Lazertinib with Amivantamab Intravenous (IV) Infusion
Lazertinib 240 mg will be administered orally once. Participants will receive amivantamab, 1050 mg or 1400 mg depending on the body weight as an IV infusion. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the LTE Phase.
干预措施: Lazertinib (Drug)
Arm A: Lazertinib with Amivantamab SC-CF
Lazertinib 240 milligrams (mg) will be administered orally once daily. Participants will receive amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), 1600 mg/ 2240 mg depending on the body weight by manual injection. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the long-term extension (LTE) Phase.
干预措施: Lazertinib (Drug)
Arm B: Lazertinib with Amivantamab Intravenous (IV) Infusion
Lazertinib 240 mg will be administered orally once. Participants will receive amivantamab, 1050 mg or 1400 mg depending on the body weight as an IV infusion. Participants benefiting from study treatment after primary analysis may continue to receive access to study treatment within the study by transferring to the LTE Phase.
干预措施: Amivantamab Intravenous (Drug)
结局指标
主要结局
For All Regions Other Than the European Union (EU) and Others Accepting Cycle 2 Day 1: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State
时间窗: Pre-dose on Cycle 4 Day 1 (each cycle of 28 days)
Ctrough was the observed serum concentration of Amivantamab at steady state immediately prior to the next drug administration.
For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab
时间窗: Pre-dose on Cycle 2 Day 1 (each cycle of 28 days)
Ctrough was the observed serum concentration of Amivantamab immediately prior to the next drug administration.
Area Under the Concentration (AUC) Time Curve of Amivantamab From Day 1 to Day 15 (AUC [Day 1-15]) of Cycle 2
时间窗: Cycle 2: Arm A: pre-dose, 24, 48, 72, 96, 168, and 360 hours (hrs) post-dose on Day 1; Arm B: pre-infusion, end of infusion (EOI)+10 minutes, EOI+2, EOI+6, EOI+24, EOI+48, EOI+72, EOI+168, and EOI+360 hrs post dose on Day 1
AUC (Day 1-15) defined as area under the concentration time curve from Cycle 2 Day 1 to Day 15 were reported.
次要结局
- Objective Response Rate (ORR)(Up to 3 years 4 months)
- Progression-Free Survival (PFS)(Up to 3 years 4 months)
- Duration of Response (DOR)(Up to 3 years 4 months)
- Time to Response (TTR)(Up to 3 years 4 months)
- Number of Participants With Adverse Events (AEs)(Up to 3 years 4 months)
- Number of Participants With AEs by Severity(Up to 3 years 4 months)
- Number of Participants With Clinical Laboratory Abnormalities(Up to 3 years 4 months)
- Number of Participants With Clinical Laboratory Abnormalities by Severity(Up to 3 years 4 months)
- Number of Participants With Infusion Related Reactions (IRRs)(Up to 3 years 4 months)
- Number of Participants With IRRs by Severity(Up to 3 years 4 months)
- For All Regions Other Than the EU and Others Accepting Cycle 2 Day 1: Observed Serum Concentration (Ctrough) of Amivantamab at Pre-dose on Cycle 2 Day 1(Pre-dose on Cycle 2 Day 1 (each cycle of 28 days))
- For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle 4 Day 1(Pre-dose on Cycle 4 Day 1 (each cycle of 28 days))
- Model-Predicted Area Under the Concentration Time Curve of Amivantamab at Steady State From Day 1 to Day 15 (AUC [Day 1-15]) of Cycle 4(Cycle 4: Arm A: pre-dose, 24, 48, 72, 96, 168, and 360 hrs post-dose on Day 1; Arm B: preinfusion, EOI+10 minutes, EOI+2, EOI+6, EOI+24, EOI+48, EOI+72, EOI+168, and EOI+360 hrs post dose on Day 1)
- Percentage of Participants With Presence of Anti-amivantamab Antibodies and Anti-rHuPH20 Antibodies(Up to 3 years 4 months)
- Percentage of Participants With Cancer Therapy Satisfaction as Assessed by Therapy Administration Satisfaction Questionnaire (TASQ)(Up to 3 years 4 months)
- Change From Baseline in Therapy Administration Satisfaction Questionnaire (TASQ) as Assessed Over Time(From baseline (Day 1, Cycle 1) to 3 years 4 months (each cycle of 28 days))
- Participant Chair Time(Up to 3 years 4 months)
- Participant Chair Time in Treatment Room(Up to 3 years 4 months)
- Duration of Treatment Administration(Up to 3 years 4 months)
- Active Health Care Professional (HCP) Time For Drug Preparation, Treatment Administration and Post-treatment Monitoring(Up to 3 years 4 months)