A Randomized, Open-label, Phase 3 Study of MK-2870 vs. Platinum Doublets in Participants With EGFR-mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 550
- 试验地点
- 313
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to evaluate sacituzumab tirumotecan versus pemetrexed in combination with carboplatin for the treatment of epidermal growth factor receptor (EGFR)-mutated advanced non-squamous non-small cell lung cancer (NSCLC). Participants in this study have NSCLC that has continued to progress on prior treatment with EGFR tyrosine kinase inhibitors (TKIs).
The primary hypotheses of this study is that sacituzumab tirumotecan is better than platinum-based doublet chemotherapy (pemetrexed and carboplatin) in regard to overall survival (OS).
详细描述
Participants will be randomized 1:1 into two arms:
- Sacituzumab tirumotecan
- Pemetrexed plus Carboplatin
Participants will receive treatment until any of the criteria for discontinuation of study intervention are met.
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
- Single (Outcomes Assessor)
盲法说明
Unblinded Open-label
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
- •Histologically or cytologically confirmed diagnosis of advanced-stage nonsquamous non-small cell lung cancer (NSCLC).
- •Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to Grade ≤1 or baseline.
- •Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load.
- •Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
- •Life expectancy of at least 3 months.
排除标准
- •Predominantly squamous cell histology NSCLC.
- •History of second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.
- •Grade ≥2 peripheral neuropathy.
- •History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
- •Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease.
- •Uncontrolled, or significant cardiovascular disease or cerebrovascular disease.
- •Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
- •Received radiation therapy to the lung that is >30 Gray within 6 months of the first dose of study intervention.
- •Known active central nervous system metastases and/or carcinomatous meningitis.
- •Active infection requiring systemic therapy.
- •History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- •Concurrent active HBV and HCV infection.
- •History of allogeneic tissue/solid organ transplant.
- •Participants who have not adequately recovered from major surgery or have ongoing surgical complications.
研究组 & 干预措施
Pemetrexed Plus Carboplatin
Participants receive, via IV infusion, 500 mg/m2 pemetrexed every 3 weeks (Days 1 and 22 of every 6-week cycle) plus area under the curve (AUC) 5 mg/mL*min carboplatin every 3 weeks (Days 1 and 22 of every 6-week cycle for 4 doses), then 500 mg/m2 pemetrexed every 3 weeks until discontinuation criteria is met.
干预措施: Pemetrexed (Drug)
Sacituzumab tirumotecan
Participants receive 4 mg/kg sacituzumab tirumotecan via intravenous (IV) infusion every 2 weeks (Days 1, 15, and 29 of every 6-week cycle) until discontinuation criteria is met.
干预措施: H2 Receptor Antagonist (Drug)
Sacituzumab tirumotecan
Participants receive 4 mg/kg sacituzumab tirumotecan via intravenous (IV) infusion every 2 weeks (Days 1, 15, and 29 of every 6-week cycle) until discontinuation criteria is met.
干预措施: Steroid Mouthwash (dexamethasone or equivalent) (Drug)
Sacituzumab tirumotecan
Participants receive 4 mg/kg sacituzumab tirumotecan via intravenous (IV) infusion every 2 weeks (Days 1, 15, and 29 of every 6-week cycle) until discontinuation criteria is met.
干预措施: H1 Receptor Antagonist (Drug)
Sacituzumab tirumotecan
Participants receive 4 mg/kg sacituzumab tirumotecan via intravenous (IV) infusion every 2 weeks (Days 1, 15, and 29 of every 6-week cycle) until discontinuation criteria is met.
干预措施: Acetaminophen (or equivalent) (Drug)
Sacituzumab tirumotecan
Participants receive 4 mg/kg sacituzumab tirumotecan via intravenous (IV) infusion every 2 weeks (Days 1, 15, and 29 of every 6-week cycle) until discontinuation criteria is met.
干预措施: Sacituzumab tirumotecan (Biological)
Pemetrexed Plus Carboplatin
Participants receive, via IV infusion, 500 mg/m2 pemetrexed every 3 weeks (Days 1 and 22 of every 6-week cycle) plus area under the curve (AUC) 5 mg/mL*min carboplatin every 3 weeks (Days 1 and 22 of every 6-week cycle for 4 doses), then 500 mg/m2 pemetrexed every 3 weeks until discontinuation criteria is met.
干预措施: Carboplatin (Drug)
Sacituzumab tirumotecan
Participants receive 4 mg/kg sacituzumab tirumotecan via intravenous (IV) infusion every 2 weeks (Days 1, 15, and 29 of every 6-week cycle) until discontinuation criteria is met.
干预措施: Dexamethasone (or equivalent) (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to approximately 51 months
Progression-Free Survival is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first. PFS for all randomized participants will be reported.
Overall Survival (OS)
时间窗: Up to approximately 51 months
Overall survival is defined as the time from randomization to death due to any cause. Overall survival for all randomized participants will be reported.
次要结局
- Progression-Free Survival (PFS)(Up to approximately 51 months)
- Objective Response Rate (ORR)(Up to approximately 51 months)
- Duration of Response (DOR)(Up to approximately 51 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and up to approximately 6 years)
- Change From Baseline in the Dyspnea (Item 8) Score, on the EORTC QLQ-C30(Baseline and up to approximately 6 years)
- Change from Baseline in the Cough (Item 31) Score, on the EORTC Lung-Cancer specific Quality of Life Questionnaire (QLQ-LC13)(Baseline and up to approximately 6 years)
- Change from Baseline in the Chest Pain (Item 40) Score, on the EORTC QLQ-LC13(Baseline and up to approximately 6 years)
- Time to Deterioration (TTD) in Global Health Status/Quality of Life (Items 29 and 30) Combined Score, on the EORTC QLQ-C30(Baseline and up to approximately 6 years)
- TTD in the Dyspnea (Item 8) Score, on the EORTC QLQ-C30(Baseline and up to approximately 6 years)
- TTD in the Cough (Item 31) Score, on the EORTC QLQ-LC13(Baseline and up to approximately 6 years)
- TTD in the Chest Pain (Item 40) Score, on the EORTC QLQ-LC13(Baseline and up to approximately 6 years)
- Number of Participants Who Experience One or More Adverse Events (AEs)(Up to approximately 6 years)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 6 years)