Randomized Open-Label Phase III Study of Sacituzumab Govitecan Versus Treatment of Physician’s Choice in Subjects with Metastatic or Locally Advanced Unresectable Urothelial Cancer

Gilead Sciences Inc.36 个研究点分布在 8 个国家目标入组 391 人开始时间: 2024年10月29日最近更新: 2025年5月13日

试验速览

阶段: 3 期
状态: 招募中
发起方: Gilead Sciences Inc.
入组人数: 391
试验地点: 36
主要终点: OS

研究概览入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

To assess overall survival (OS) with sacituzumab govitecan in comparison with treatment of physician’s choice (TPC) in subjects with metastatic or locally advanced unresectable urothelial cancer (UC)

研究设计

研究类型: Interventional

入排标准

年龄范围: 18 years 至 65+ years（18-64 Years, 65+ Years）
接受健康志愿者: 否

入选标准

•Subjects meeting all of the following inclusion criteria at Screening/Baseline will be eligible for participation in the study: Female or male subjects, ≥18 years of age, able to understand and give written informed consent.
•Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 6 of the protocol
•Subjects with histologically documented UC that is metastatic or locally advanced unresectable defined as Tumor (T) 4b, any node (N) or Any T, N 2-3
•Tumors of upper and lower urinary tract are permitted. Mixed histologic types are allowed if urothelial is the predominant histology.
•ECOG performance status (PS) score of 0 or
•Subjects with progression or recurrence following receipt of platinum-containing regimen and anti-PD-1/PD-L1 therapy for metastatic or locally advanced unresectable disease will be enrolled. a) Subjects with recurrence or progression ≤12 months following completion of cisplatincontaining chemotherapy given in the neo-adjuvant/adjuvant setting may utilize that line of therapy to be eligible for the study. The 12-month period is counted from completion of surgical intervention or cisplatin therapy, respectively. These subjects must receive anti-PD-1/PD L1 therapy in the metastatic or locally advanced unresectable setting to be eligible. b) Subjects who received either carboplatin or anti-PD-1/PD-L1 therapy in the neoadjuvant/ adjuvant setting will not be able to count that line of therapy towards eligibility for the study. c) Cisplatin-ineligible subjects who meet one of the below criteria and who were treated with carboplatin in the metastatic or locally advanced unresectable settings may count that line of therapy towards eligibility. They must then have received anti-PD-1/PD-L1 therapy in metastatic or locally advanced unresectable setting to be eligible for the study. Cisplatin ineligibility is defined as meeting one of the following criteria: i) Creatinine Clearance <60 mL/min ii) Grade ≥2 Audiometric Hearing Loss iii) Grade ≥2 Peripheral Neuropathy iv) New York Heart Association (NYHA) Class III heart failure v) ECOG PS ≥2 d) Anti-PD-1/PD-L1 therapy administered as part of maintenance therapy may be counted towards eligibility for the study e) Subjects who have progressed after receiving enfortumab vedotin in prior lines of therapy, and subjects who are either ineligible or unable to tolerate enfortumab vedotin therapy, are eligible to enroll in the study. f) Subjects who received only concurrent chemoradiation for bladder preservation without further systemic therapy are not eligible to enroll in the study. The substitution of carboplatin for cisplatin does not constitute a new regimen provided no new chemotherapeutic agents were added to the regimen and no progression was noted prior to the change in platinum.
•Subjects with previously treated brain metastases may participate in the study provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and stabilization of all neurologic symptoms, have no evidence of new or enlarging brain metastases, and are not using steroids >20 mg of prednisone (or equivalent) daily for brain metastases for at least 7 days prior to first dose of the study drug.
•Adequate hematologic counts without transfusion or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥9 g/dL, absolute neutrophil count [ANC] ≥1,500/mm3, and platelets ≥100,000/μL).
•Adequate hepatic function (bilirubin ≤1.5 x institutional upper limit of normal [IULN], aspartate aminotransferase [AST] and alanine aminotransferase [ALT] ≤2.5 x IULN or ≤5 x IULN if known liver metastases and serum albumin ≥3 g/dL). Docetaxel will only be option in TPC arm for subjects with a total bilirubin ≤1 x IULN, and an AST and/or ALT ≤1.5 x IULN if alkaline phosphatase is also >2.5 x IULN.
•Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation or other validated instruments (eg Modification of Diet in Renal Disease [MDRD] equation).

排除标准

•Subjects meeting any of the following exclusion criteria at Screening/Baseline will not be enrolled in the study: Women who are pregnant or lactating (see Appendix 6).
•Have uncontrolled HIV-1/2 viral load (ie, ≥ 200 copies/mL and/or CD4+ count < 350 cells/mm3) and/or on medications that may interfere with SN-38 metabolism.
•Have active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In subjects with a history of HBV or HCV, subjects with a detectable viral load will be excluded.
•Have other concurrent medical or psychiatric conditions that, in the investigator’s opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
•Have inability to tolerate or are allergic to any potential TPC agent or sacituzumab govitecan or unable or unwilling to receive the doses specified in the protocol.
•Have inability to complete all specified study procedures for any reason.
•History of active interstitial lung disease or noninfectious pneumonitis.
•Have had a prior anti-cancer mAb/ADC within 4 weeks prior to C1D1 or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to C1D
•Subjects participating in observational studies are eligible.
•Have received prior chemotherapy for UC with any available SOC therapies in the control arm (ie, either prior paclitaxel and docetaxel in countries where vinflunine is not an approved therapy, or either prior paclitaxel, docetaxel and vinflunine in countries where vinflunine is approved and is commercially available).
•Have not recovered (ie, ≤Grade 1) from AEs due to previously administered chemotherapeutic agent. Note: Subjects with ≤Grade 2 neuropathy or any grade of alopecia are an exception to this criterion and will qualify for the study. Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy.
•Have previously received topoisomerase 1 inhibitors.
•Have an active second malignancy. Note: Subjects with a history of malignancy that have been completely treated and with no evidence of active cancer for 3 years prior to enrollment, or subjects with surgically cured tumors with low risk of recurrence are allowed to enroll in the study after discussion with the medical monitor
•Have active cardiac disease, defined as: a) Myocardial infarction or unstable angina pectoris within 6 months of C1D
•b) History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation. c) NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of <40%.
•Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or gastrointestinal (GI) perforation within 6 months of enrollment.
•Have an active serious infection requiring anti-infective therapy (Contact medical monitor for clarification).

结局指标

主要结局

次要结局

Change from baseline in the physical functioning, global health status, pain, and fatigue scales of the EORTC QLQ-C30 score
PFS by investigator assessment and BICR using RECIST v1.1
ORR, CBR and DOR by investigator assessment and BICR using RECIST v1.1
Safety and tolerability evaluated by AEs, SAEs, and laboratory changes

研究者

发起方

Gilead Sciences Inc.

申办方类型

Pharmaceutical company

责任方

Principal Investigator

主要研究者

EU CT Support

Scientific

Gilead Sciences Inc.

研究点 (36)

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