2024-511957-23-00招募中3 期
A Randomized, Open-label, Phase 3 Study of Sacituzumab Govitecan Versus Treatment of Physician’s Choice in Participants With Endometrial Cancer Who Have Received Prior Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Immunotherapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 179
- 试验地点
- 55
- 主要终点
- PFS, defined as the time from the date of randomization until the date of objective progressive disease (PD), as assessed by BICR per RECIST v1.1, or death from any cause, whichever comes first
研究概览
简要总结
- To compare the effect of sacituzumab govitecan (SG) relative to treatment of physician’s choice (TPC) on progression-free survival (PFS) as assessed by blinded independent central review (BICR) a) Hypothesis (H1): SG is superior to TPC as assessed by PFS by BICR in participants without carcinosarcoma histology. b) Hypothesis (H3): SG is superior to TPC as assessed by PFS by BICR in all-comer participants.
- To compare the effect of SG relative to TPC on overall survival (OS) a) Hypothesis (H2): SG is superior to TPC as assessed by OS in participants without carcinosarcoma histology. b) Hypothesis (H4): SG is superior to TPC as assessed by OS in all-comer participants.
- Hypothesis (H5): SG is superior to TPC as assessed by ORR in all-comer participants with measurable disease at baseline.
- Hypothesis (H6): SG is superior to TPC as assessed by change from baseline at Week 16 in physical function in all-comer participants.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Willing and able to comply with the requirements and restrictions in this protocol.
- •Participants assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception(Section 11.5).
- •Life expectancy of ≥ 3 months
- •Participants assigned female at birth, 18 years of age or older (or minimum age according to country-specific requirements), and able to understand and give written informed consent.
- •Documented evidence of recurrent/persistent endometrial cancer (endometrial carcinoma or carcinosarcoma)
- •Up to 3 prior lines of systemic therapy for endometrial cancer, including systemic platinum-based chemotherapy and anti-PD-1/PD-L1 therapy, either in combination or separately. - Neoadjuvant and/or adjuvant therapy is considered 1 prior line of systemic therapy. - Concurrent chemotherapy given during radiotherapy with radio-sensitizing intent (eg, cisplatin during external beam radiotherapy) will not be counted as a separate line of therapy. However, if systemic chemotherapy is given before or after radiotherapy, this would be considered as a separate line of therapy. - Prior monoclonal antibodies or targeted therapies, including but not limited to bevacizumab, poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis), trastuzumab, will count as a line of treatment if given as a single agent with the intent of controlling disease. If these agents are given in combination with chemotherapy and continued as maintenance monotherapy, they will not be counted as a separate line of treatment. Additionally, maintenance therapy with a PARPi or selinexor will not be counted as a separate line of therapy. - There is no restriction regarding prior hormonal or hormonal-based therapy. Hormonal or hormonal-based therapy does not count as a line of therapy. However, if hormonal therapy is combined with a targeted agent (eg, mammalian target of rapamycin [mTOR] inhibitor [everolimus] or cyclin-dependent kinase [CDK]4/6 inhibitor), this would count as a separate line of therapy. - For participants who are ineligible for anti-PD-1/PD-L1 therapy due to medical comorbidities, or if anti-PD-1/PD-L1 agents are not available as standard-of-care therapy in any line of treatment according to local standards, prior treatment with an anti-PD-1/PD-L1 agent is not required.
- •Eligible for treatment with either doxorubicin or paclitaxel as determined by the investigator. Participants must not have any contraindications to receive treatment with doxorubicin or paclitaxel as per the locally approved product label.
- •Radiologically evaluable disease (either measurable or nonmeasurable) by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria by investigator assessment. - If a participant has disease based on pleural effusion or ascites alone (with no other radiologically evaluable lesions), this must be cytologically confirmed. - Participants who require drainage of a fluid-based nontarget lesion (eg, paracentesis or thoracentesis) every 8 weeks or more frequently, are not eligible.
- •Documented disease progression by CT or MRI during or after the most recent therapy per RECIST v1.1 criteria by investigator assessment.
- •Availability of tumor tissue from an archival or fresh biopsy for assessment of Trop-2 and other study biomarkers. Tissue submission should be in the form of a formalin-fixed paraffin-embedded block (preferably) or ≥ 20 freshly sectioned, unstained slides. Tissue must be submitted within 4 weeks of randomization. - If archival tumor tissue is available, it should preferably be from the most recently available tumor biopsy (obtained ideally within 12 months prior to randomization), from a locally recurrent or metastatic site. If archival tissue is not available, a fresh biopsy, preferably from a locally recurrent or metastatic site should be performed before randomization. Aspirate samples (eg, fine needle aspirates, endometrial aspirates), bone biopsies, and cytology samples are not suitable samples. If < 20 unstained slides are available, and it is not clinically feasible to obtain a new biopsy, the participant may still be eligible upon consultation with the sponsor medical monitor.
- •Eastern Cooperative Oncology Group PS of 0 or 1 (see Appendix 11.7).
排除标准
- •Need for ongoing systemic anticancer therapies aside from the study treatment.
- •Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In participants with a history of HBV or HCV, participants with detectable viral loads will be excluded. 10.1 Participants who test positive for hepatitis B surface antigen are excluded. Participants who test positive for hepatitis B core antibody will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease. 10.2 Participants who test positive for HCV antibody will require HCV RNA by quantitative PCR for confirmation of active disease. Participants with a known history of HCV or a positive HCV antibody test will not require an HCV antibody at screening and will only require HCV RNA by quantitative PCR for confirmation of active disease.
- •Uterine leiomyosarcoma and endometrial stromal sarcomas are excluded.
- •Scheduled surgery during the study, other than a minor surgery that would not delay study treatment.
- •Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or gastrointestinal perforation within 6 months prior to randomization.
- •Have a positive serum pregnancy test at screening or enrollment or have plans to breastfeed during the study period and for 1 month following the last dose of study intervention.
- •Use of any live vaccine against infectious diseases within 30 days of the first dose of study drug.
- •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.
- •Any medical condition that, in the investigator’s or sponsor’s opinion, poses an undue risk to the participant’s participation in the study.
- •Participants who are candidates for curative-intent therapy at the time of study enrollment.
- •Participants eligible for rechallenge with platinum-based chemotherapy as determined by the investigator.
- •Known or severe (Grade 3 or higher) hypersensitivity to SG and/or the chemotherapy regimen of choice in the TPC group (eg doxorubicin or paclitaxel), their metabolites, or formulation excipients.
- •Received any prior treatment with a Trop-2-directed ADC.
- •Received any prior treatment (including an ADC) containing a chemotherapeutic agent targeting topoisomerase I.
- •Have had a prior anticancer biologic agent within 4 weeks prior to the first dose of study drug or have had prior chemotherapy, targeted small molecule therapy, hormonal or hormonal-based therapy, or radiation therapy within 2 weeks prior to the first dose of study drug.
- •Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of study drug.Note: Use of investigational anti-PD-1/PD-L1 agents are acceptable if the last dose was longer than 28 days prior to first dose of study drug.
- •Have not recovered (ie, Grade 2 or higher is considered not recovered) from AEs due to a previously administered agent. Participants with Grade 2 or lower neuropathy or any grade alopecia are an exception to this criterion and will qualify for the study. Participants with immune-mediated endocrine AEs Grade 2 or lower requiring treatment or hormone replacement are eligible. If participants underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Participants who underwent major surgery within 3 weeks of randomization are not eligible.
- •Requirement for ongoing therapy with any prohibited medications listed in Section 5.6.
- •Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable CNS disease for ≥ 4 weeks prior to randomization and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are taking 10 mg/day or less of prednisone or its equivalent. All participants with carcinomatous meningitis are excluded regardless of clinical stability.
- •Have an active second malignancy. 5.1 Participants with a history of malignancy that have been completely treated, with noevidence of active cancer for 3 years prior to randomization, or participants with surgically cured tumors with low risk of recurrence (eg, nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll.
- •Left ventricular ejection fraction < 50% on screening echocardiogram or multigated acquisition (scan).
- •Have a history of significant cardiovascular disease, defined as: 7.1 Myocardial infarction or unstable angina pectoris within 6 months of randomization. 7.2 History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation. 7.3 New York Heart Association Class III or greater congestive heart failure.
- •Have an active serious infection requiring systemic antimicrobial therapy.
- •Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody at screening) with detectable viral load. HIV testing is not required and can be done if clinically indicated and per local standard of care.
研究组 & 干预措施
Trodelvy 200 mg powder for concentrate for solution for infusion
Test
干预措施: Trodelvy 200 mg powder for concentrate for solution for infusion (Drug)
Doxorubicin Teva 2 mg/ml Concentrate for Solution for Infusion
Comparator
干预措施: Doxorubicin Teva 2 mg/ml Concentrate for Solution for Infusion (Drug)
PACLITAXEL
Comparator
干预措施: PACLITAXEL (Drug)
结局指标
主要结局
PFS, defined as the time from the date of randomization until the date of objective progressive disease (PD), as assessed by BICR per RECIST v1.1, or death from any cause, whichever comes first
PFS, defined as the time from the date of randomization until the date of objective progressive disease (PD), as assessed by BICR per RECIST v1.1, or death from any cause, whichever comes first
OS, defined as the time from the date of randomization until death due to any cause
OS, defined as the time from the date of randomization until death due to any cause
次要结局
- ORR, defined as the percentage of participants who have achieved a CR or PR as best overall response that is confirmed ≥ 4 weeks after initial documentation of response as assessed by BICR per RECIST v1.1
- Change from baseline in the physical functioning domain of the European Organisation for Research and Treatment of Cancer quality of life Questionnaire-Core 30 Version 3.0 (EORTC QLQ-C30) at Week 16
- PFS, defined as the time from the date of randomization until the date ofobjective PD, as assessed by investigator per RECIST v1.1, or death from any cause, whichever comes first
- ORR, defined as the percentage of participants who have achieved a CR or PR as best overall response that is confirmed ≥ 4 weeks after initial documentation of response as assessed by investigator per RECIST v1.1
- DOR, defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive PD as assessed by BICR and investigator per RECIST v1.1, or death from any cause, whichever comes first
- CBR, defined as the percentage of participants with best overall response of CR or PR that is confirmed ≥ 4 weeks after initial documentation of response or durable stable disease (SD; duration of SD ≥ 6 months from randomization to disease progression), as assessed by BICR and investigator perRECIST v1.1
- Incidence of treatment-emergent adverse events (TEAEs) and clinical laboratory abnormalities
- Change from baseline in GHS/QoL domain of the EORTC QLQ-C30 at Week 16
研究者
EU CT Support
Scientific
Gilead Sciences Inc.
研究点 (55)
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