A Phase 3 Randomized, Active-controlled, Open-label, Multicenter Study to Compare the Efficacy and Safety of MK-2870 Monotherapy Versus Treatment of Physician's Choice as Second-line Treatment for Participants With Recurrent or Metastatic Cervical Cancer (TroFuse-020/GOG-3101/ENGOT-cx20)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 686
- 试验地点
- 478
- 主要终点
- Number of Participants Discontinuing Study Treatment Due to an AE in Sacituzumab Tirumotecan Run-in
研究概览
简要总结
This study will have two phases: a sacituzumab tirumotecan safety run-in and a Phase 3 portion. The safety run-in phase will be used to evaluate the efficacy and safety of sacituzumab tirumotecan at the dose for evaluation in the Phase 3 portion. The purpose of this study is to compare the efficacy and safety of sacituzumab tirumotecan versus treatment of physician's choice as second-line treatment for participants with recurrent or metastatic cervical cancer in the Phase 3 portion.
The primary study hypotheses are that, in the Phase 3 portion, sacituzumab tirumotecan results in a superior overall survival compared to TPC in participants with high trophoblast cell surface antigen 2 (TROP2) expression level and in all participants.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Has histologically-confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix
- •Must have recurrent or metastatic cervical cancer that has progressed on or after treatment with 1 prior line of systemic platinum doublet chemotherapy (with or without bevacizumab) AND must have received anti-PD-1/anti-PD-L1 therapy as part of prior cervical cancer regimens
- •Has measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions
- •Is assigned female sex at birth, at least 18 years of age at the time of providing the informed consent
- •Has ECOG performance status of 0 or 1 within 7 days before allocation for the Sacituzumab Tirumotecan Run-in or within 7 days before randomization for the Phase 3 portion
- •Has provided tumor tissue (most recent sample is preferred) from a core or excisional biopsy of a tumor lesion not previously irradiated
- •HIV-infected participants must have well controlled human immunodeficiency virus (HIV) on antiretroviral therapy (ART)
- •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 prior to allocation (Sacituzumab Tirumotecan Run-in) or randomization (Phase 3 portion)
- •Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
- •Has adequate organ function
排除标准
- •Has Grade ≥2 peripheral neuropathy
- •Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
- •Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
- •Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
- •Received prior systemic anticancer therapy
- •Received prior radiotherapy within 2 weeks of start of study intervention, or has 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 is allowed
- •Has other histological subtypes of cervical cancer apart from squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma (eg, carcinosarcoma), or has a diagnosis of nonepithelial cancer (eg, sarcoma, neuroendocrine tumors) of the cervix.
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Active infection requiring systemic therapy
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Concurrent active Hepatitis B and active Hepatitis C virus infection
- •Severe hypersensitivity (≥Grade 3) to sacituzumab tirumotecan or treatment of physician's choice (TPC) and/or any of their excipients, or other biologic therapy
- •Participants who have not adequately recovered from major surgery or have ongoing surgical complications
- •Has a history of (noninfectious) pneumonitis/ILD that required steroids or has current pneumonitis/ILD
研究组 & 干预措施
Treatment of Physician's Choice (TPC)
At the physician's discretion, participants will receive 500 mg/m^2 of pemetrexed on day 1 of every 3-week cycle via IV infusion OR 2 mg/kg of tisotumab vedotin on day 1 of every 3-week cycle via IV infusion OR 1 mg/m^2 (or 1.25 mg/m^2 if tolerating well) topotecan on days 1, 2, 3, 4, and 5 of every 3-week cycle via IV infusion OR 30 mg/m^2 of vinorelbine on days 1 and 8 of every 3-week cycle via IV infusion OR 1000 mg/m^2 of gemcitabine on day 1 and 8 of every 3-week cycle via IV infusion OR 100 mg/m^2 (or 125 mg/m^2 if tolerating well) of irinotecan on days 1, 8, 15, and 22 of every 6 week cycle via IV infusion, until progressive disease or discontinuation.
干预措施: Vinorelbine (Drug)
Treatment of Physician's Choice (TPC)
At the physician's discretion, participants will receive 500 mg/m^2 of pemetrexed on day 1 of every 3-week cycle via IV infusion OR 2 mg/kg of tisotumab vedotin on day 1 of every 3-week cycle via IV infusion OR 1 mg/m^2 (or 1.25 mg/m^2 if tolerating well) topotecan on days 1, 2, 3, 4, and 5 of every 3-week cycle via IV infusion OR 30 mg/m^2 of vinorelbine on days 1 and 8 of every 3-week cycle via IV infusion OR 1000 mg/m^2 of gemcitabine on day 1 and 8 of every 3-week cycle via IV infusion OR 100 mg/m^2 (or 125 mg/m^2 if tolerating well) of irinotecan on days 1, 8, 15, and 22 of every 6 week cycle via IV infusion, until progressive disease or discontinuation.
干预措施: Topotecan (Drug)
Sacituzumab Tirumotecan
Participants will receive 4 mg/kg of sacituzumab tirumotecan once every 2 weeks (Q2W) via intravenous (IV) infusion until progressive disease or discontinuation.
干预措施: Sacituzumab Tirumotecan (Biological)
Treatment of Physician's Choice (TPC)
At the physician's discretion, participants will receive 500 mg/m^2 of pemetrexed on day 1 of every 3-week cycle via IV infusion OR 2 mg/kg of tisotumab vedotin on day 1 of every 3-week cycle via IV infusion OR 1 mg/m^2 (or 1.25 mg/m^2 if tolerating well) topotecan on days 1, 2, 3, 4, and 5 of every 3-week cycle via IV infusion OR 30 mg/m^2 of vinorelbine on days 1 and 8 of every 3-week cycle via IV infusion OR 1000 mg/m^2 of gemcitabine on day 1 and 8 of every 3-week cycle via IV infusion OR 100 mg/m^2 (or 125 mg/m^2 if tolerating well) of irinotecan on days 1, 8, 15, and 22 of every 6 week cycle via IV infusion, until progressive disease or discontinuation.
干预措施: Tisotumab Vedotin (Biological)
Treatment of Physician's Choice (TPC)
At the physician's discretion, participants will receive 500 mg/m^2 of pemetrexed on day 1 of every 3-week cycle via IV infusion OR 2 mg/kg of tisotumab vedotin on day 1 of every 3-week cycle via IV infusion OR 1 mg/m^2 (or 1.25 mg/m^2 if tolerating well) topotecan on days 1, 2, 3, 4, and 5 of every 3-week cycle via IV infusion OR 30 mg/m^2 of vinorelbine on days 1 and 8 of every 3-week cycle via IV infusion OR 1000 mg/m^2 of gemcitabine on day 1 and 8 of every 3-week cycle via IV infusion OR 100 mg/m^2 (or 125 mg/m^2 if tolerating well) of irinotecan on days 1, 8, 15, and 22 of every 6 week cycle via IV infusion, until progressive disease or discontinuation.
干预措施: Pemetrexed (Drug)
Treatment of Physician's Choice (TPC)
At the physician's discretion, participants will receive 500 mg/m^2 of pemetrexed on day 1 of every 3-week cycle via IV infusion OR 2 mg/kg of tisotumab vedotin on day 1 of every 3-week cycle via IV infusion OR 1 mg/m^2 (or 1.25 mg/m^2 if tolerating well) topotecan on days 1, 2, 3, 4, and 5 of every 3-week cycle via IV infusion OR 30 mg/m^2 of vinorelbine on days 1 and 8 of every 3-week cycle via IV infusion OR 1000 mg/m^2 of gemcitabine on day 1 and 8 of every 3-week cycle via IV infusion OR 100 mg/m^2 (or 125 mg/m^2 if tolerating well) of irinotecan on days 1, 8, 15, and 22 of every 6 week cycle via IV infusion, until progressive disease or discontinuation.
干预措施: Irinotecan (Drug)
Treatment of Physician's Choice (TPC)
At the physician's discretion, participants will receive 500 mg/m^2 of pemetrexed on day 1 of every 3-week cycle via IV infusion OR 2 mg/kg of tisotumab vedotin on day 1 of every 3-week cycle via IV infusion OR 1 mg/m^2 (or 1.25 mg/m^2 if tolerating well) topotecan on days 1, 2, 3, 4, and 5 of every 3-week cycle via IV infusion OR 30 mg/m^2 of vinorelbine on days 1 and 8 of every 3-week cycle via IV infusion OR 1000 mg/m^2 of gemcitabine on day 1 and 8 of every 3-week cycle via IV infusion OR 100 mg/m^2 (or 125 mg/m^2 if tolerating well) of irinotecan on days 1, 8, 15, and 22 of every 6 week cycle via IV infusion, until progressive disease or discontinuation.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Number of Participants Discontinuing Study Treatment Due to an AE in Sacituzumab Tirumotecan Run-in
时间窗: Up to approximately 51 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Number of Participants Experiencing One or More Adverse Events (AEs) in Sacituzumab Tirumotecan Run-in
时间窗: Up to approximately 51 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Overall Survival (OS) in Phase 3 Portion
时间窗: Up to approximately 43 months
OS is defined as the time from randomization to death due to any cause.
Objective Response Rate (ORR) in Sacituzumab Tirumotecan Run-in
时间窗: Up to approximately 51 months
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
次要结局
- Change from Baseline in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score in Phase 3 Portion(Baseline and up to approximately 51 months)
- Progression-free Survival (PFS) in Phase 3 Portion(Up to approximately 43 months)
- Change from Baseline in EORTC QLQ-C30 Role Functioning Score in Phase 3 Portion(Baseline and up to approximately 51 months)
- Duration of Response (DOR) in Phase 3 Portion(Up to approximately 43 months)
- Number of Participants Discontinuing Study Treatment Due to an AE in Phase 3 Portion(Up to approximately 51 months)
- Time to First Deterioration (TTD) in European Organisation 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 in Phase 3 Portion(Baseline and up to approximately 51 months)
- Change from Baseline in EORTC QLQ-C30 Physical Functioning Score in Phase 3 Portion(Baseline and up to approximately 51 months)
- ORR in Phase 3 Portion(Up to approximately 43 months)
- Number of Participants Experiencing One or More AEs in Phase 3 Portion(Up to approximately 51 months)