A Phase 3, Multicenter, Open-label, Randomized Study to Compare the Efficacy and Safety of MK-2870 Versus Treatment of Physician's Choice in 3L+ Advanced/Metastatic Gastroesophageal Adenocarcinoma (Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, and Esophageal Adenocarcinoma)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 450
- 试验地点
- 331
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This study will compare how safe and effective sacituzumab tirumotecan is versus the treatment of physician's choice (TPC) in participants with advanced/metastatic gastroesophageal adenocarcinoma. The primary hypothesis of this study is sacituzumab tirumotecan is superior to TPC with respect to Overall Survival (OS).
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)
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
- •Has a histologically-or cytologically-confirmed diagnosis of advanced, unresectable or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma
- •Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology. Lesions situated in a previously-irradiated area are considered measurable if progression has been shown in such lesions.
- •Has received, and progressed on, at least 2 prior chemotherapy and/or immunotherapy regimens for advanced, unresectable or metastatic gastroesophageal adenocarcinoma.
- •Participants are eligible regardless of human epidermal growth factor receptor-2 (HER2) status. Participants who are HER2+ must have previously received trastuzumab where available/appropriate
- •Has adequate organ function
- •Has provided tumor tissue sample for determination of trophoblast cell-surface antigen 2 (TROP2) status by the central laboratory before randomization for stratification
- •Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline (except for alopecia and vitiligo). Participants with endocrine related AEs who are adequately treated with hormone replacement therapy are eligible
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days before randomization
- •Has ability to swallow oral medication for those who may receive trifluridine-tipiracil
- •Human immunodeficiency virus (HIV)-infected participants must have well-controlled HIV on antiretroviral therapy (ART)
- •Hepatitis B surface antigen (HBsAg)-positive participants are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
- •Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
排除标准
- •Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
- •Has Grade ≥2 peripheral neuropathy
- •Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea)
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of corrected QT interval (QTcF) to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the first dose of study intervention
- •Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before the first dose of study intervention
- •Has received prior treatment with a trophoblast antigen 2(TROP2) targeted antibody-drug conjugate (ADC), a topoisomerase 1 inhibitor based, and/or a topoisomerase 1 inhibitor-based chemotherapy.
- •Has received prior systemic anticancer therapy within 2 weeks before the first dose of study intervention
- •Has received prior radiotherapy within 2 weeks before the first dose of study intervention, has radiation-related toxicities, requiring corticosteroids, and/or has had radiation pneumonitis
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- •Is currently receiving a strong and/or moderate inducer/inhibitor of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of treatment with study intervention. The required washout period before starting study intervention is 2 weeks
- •Has received an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has an active infection requiring systemic therapy
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castlemans's Disease
- •Has concurrent active hepatitis B (defined as hepatitis B surface antigen (HBsAg) positive and/or detectable HBV deoxyribonucleic acid (DNA)) and Hepatitis C virus (HCV) defined as anti-HCV antibody (Ab) positive and detectable HCV ribonucleic acid (RNA)) infection
- •Has had major surgery or significant traumatic injury within 4 weeks before the first dose of study intervention. Anticipation of the need for major surgery during the course of treatment with study intervention is also exclusionary
- •Has severe hypersensitivity (Grades >=3) to the study interventions, any of their excipients, and/or to another biologic therapy
- •Has a history of (noninfectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD
研究组 & 干预措施
Sacituzumab tirumotecan
Participants will receive sacituzumab tirumotecan at a dose of 4mg/kg by intravenous (IV) infusion on days 1, 15, and 29 of every 42-day cycle.
干预措施: Sacituzumab tirumotecan (Biological)
Sacituzumab tirumotecan
Participants will receive sacituzumab tirumotecan at a dose of 4mg/kg by intravenous (IV) infusion on days 1, 15, and 29 of every 42-day cycle.
干预措施: Rescue medication (Drug)
Sacituzumab tirumotecan
Participants will receive sacituzumab tirumotecan at a dose of 4mg/kg by intravenous (IV) infusion on days 1, 15, and 29 of every 42-day cycle.
干预措施: Supportive care measures (Drug)
Treatment of Physician's Choice (TPC)
TPC include either trifluridine-tipiracil (35 mg/m^2 orally (PO) twice a day (BID) on days 1 to 5 and 8 to 12 of every 28-day cycle), irinotecan (150 mg/m^2 IV on days 1 and 15 of every 28-day cycle), paclitaxel (80 mg/m^2 IV on days 1, 8, and 15 of every 28-day cycle), or docetaxel (75 mg/m^2 IV on day 1 of every 21-day cycle).
干预措施: Trifluridine-Tipiracil (Drug)
Treatment of Physician's Choice (TPC)
TPC include either trifluridine-tipiracil (35 mg/m^2 orally (PO) twice a day (BID) on days 1 to 5 and 8 to 12 of every 28-day cycle), irinotecan (150 mg/m^2 IV on days 1 and 15 of every 28-day cycle), paclitaxel (80 mg/m^2 IV on days 1, 8, and 15 of every 28-day cycle), or docetaxel (75 mg/m^2 IV on day 1 of every 21-day cycle).
干预措施: Irinotecan (Drug)
Treatment of Physician's Choice (TPC)
TPC include either trifluridine-tipiracil (35 mg/m^2 orally (PO) twice a day (BID) on days 1 to 5 and 8 to 12 of every 28-day cycle), irinotecan (150 mg/m^2 IV on days 1 and 15 of every 28-day cycle), paclitaxel (80 mg/m^2 IV on days 1, 8, and 15 of every 28-day cycle), or docetaxel (75 mg/m^2 IV on day 1 of every 21-day cycle).
干预措施: Paclitaxel (Drug)
Treatment of Physician's Choice (TPC)
TPC include either trifluridine-tipiracil (35 mg/m^2 orally (PO) twice a day (BID) on days 1 to 5 and 8 to 12 of every 28-day cycle), irinotecan (150 mg/m^2 IV on days 1 and 15 of every 28-day cycle), paclitaxel (80 mg/m^2 IV on days 1, 8, and 15 of every 28-day cycle), or docetaxel (75 mg/m^2 IV on day 1 of every 21-day cycle).
干预措施: Docetaxel (Drug)
Treatment of Physician's Choice (TPC)
TPC include either trifluridine-tipiracil (35 mg/m^2 orally (PO) twice a day (BID) on days 1 to 5 and 8 to 12 of every 28-day cycle), irinotecan (150 mg/m^2 IV on days 1 and 15 of every 28-day cycle), paclitaxel (80 mg/m^2 IV on days 1, 8, and 15 of every 28-day cycle), or docetaxel (75 mg/m^2 IV on day 1 of every 21-day cycle).
干预措施: Supportive care measures (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to ~ 31 months
OS is defined as the time from randomization to death due to any cause.
次要结局
- Progression-free survival (PFS)(Up to ~ 25 months)
- Objective Response Rate (ORR)(Up to ~ 25 months)
- Duration of Response (DOR)(Up to ~ 25 months)
- Number of Participants Who Experience an Adverse Event (AE)(Up to ~ 36 months)
- Number of Participants Who Discontinue Study Intervention Due to an AE(Up to ~ 36 months)