A Phase 3 Randomized Open-Label Study of Sacituzumab Govitecan Versus Physician's Choice in Recurrent or Persistent Endometrial Cancer Post-Chemotherapy and Immunotherapy
- Trial ID
- 2024-511957-23-00
- Protocol
- GS-US-682-6769
- Sponsor
- Gilead Sciences Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the effect of **sacituzumab govitecan** (SG) relative to treatment of physician's choice (TPC) on progression-free survival (PFS) and overall survival (OS) in participants with recurrent or persistent endometrial cancer. This is clinically relevant as it aims to determine the efficacy of SG in prolonging survival and delaying disease progression, which are critical outcomes for patients with limited treatment options following prior platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy.
Secondary objectives include:
- Comparing the effect of SG relative to TPC on the objective response rate (ORR) as assessed by blinded independent central review (BICR).
- Assessing the impact of SG versus TPC on physical function.
- Evaluating the effect of SG relative to TPC on progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and clinical benefit ratio (CBR) as assessed by both BICR and investigators.
- Evaluating the safety and tolerability of SG compared to TPC.
- Comparing the effect of SG relative to TPC on global health status/quality of life (GHS/QoL).
Participants
The clinical trial involves a total of **370 participants** who are exclusively **female** and have been diagnosed with **recurrent or persistent endometrial cancer**. The study population consists of individuals aged **18 years and older**, with no upper age limit specified. Participants were selected based on their ability to comply with the study protocol, a life expectancy of at least three months, and documented evidence of disease progression. The trial does not include any vulnerable populations. Participants must have undergone up to three prior lines of systemic therapy for endometrial cancer, including systemic platinum-based chemotherapy and anti-PD-1/PD-L1 therapy. Eligible participants must be suitable for treatment with either doxorubicin or paclitaxel, as determined by the investigator, and must not have any contraindications to these treatments. The trial does not impose specific lifestyle considerations such as diet or physical activity. Participants are required to have radiologically evaluable disease and provide tumor tissue for biomarker assessment. The selection criteria ensure that participants have a documented progression of disease and are capable of understanding and providing informed consent.
Plans and Procedures
The clinical trial is designed as a **randomized**, open-label, Phase 3 study to evaluate the efficacy of **sacituzumab govitecan** compared to the treatment of physician's choice in participants with recurrent or persistent **endometrial cancer** who have previously received platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy. The trial aims to assess progression-free survival (PFS) and overall survival (OS) as primary endpoints, with secondary endpoints including objective response rate (ORR), duration of response (DOR), and incidence of treatment-emergent adverse events (TEAEs). The study is expected to commence recruitment on December 2, 2024, and conclude by June 1, 2029.
Participants will be randomly assigned to receive either sacituzumab govitecan or a treatment regimen determined by the physician, which may include **doxorubicin hydrochloride** or **paclitaxel**. The trial will involve multiple study visits, beginning with a screening visit to confirm eligibility based on criteria such as documented evidence of endometrial cancer, prior treatment history, and radiologically evaluable disease. Participants must also provide tumor tissue for biomarker assessment. The inclusion visit will be followed by regular follow-up visits to monitor treatment response and safety, with assessments conducted using RECIST v1.1 criteria. The end-of-study visit will occur upon completion of the treatment period or in the event of disease progression or unacceptable toxicity.
The expected duration of participant involvement is contingent upon individual response to treatment, with a maximum treatment period of 21 to 28 days per cycle, depending on the assigned regimen. Conditions that may lead to early termination from the study include disease progression, adverse events, or withdrawal of consent. Participants are required to comply with protocol-specified contraceptive measures and must have a life expectancy of at least three months to be eligible for the trial. The study will be conducted in accordance with regulatory guidelines, ensuring the safety and well-being of all participants throughout the trial duration.
Treatment
The clinical trial involves the administration of **Trodelvy**, a 200 mg powder for concentrate for solution for infusion, containing the active substance **sacituzumab govitecan**. This experimental medication is an **antibody-drug conjugate** and is administered via **intravenous use**. The pharmaceutical form is a solution for infusion, and the treatment is given every 21 days. The dosage is calculated based on the participant's body weight in milligrams per kilogram (mg/kg). The maximum treatment period for this medication is 21 days. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.
In addition to the experimental treatment, the study includes a comparator treatment with **Doxorubicin Teva**, a 2 mg/ml concentrate for solution for infusion. The active substance in this comparator is **doxorubicin hydrochloride**, a **cytotoxic anthracycline antibiotic**. This medication is also administered intravenously, with the dosage determined in milligrams per square meter (mg/m²) of body surface area. The maximum treatment period for doxorubicin is 21 days, and participant compliance is closely monitored to ensure proper administration.
Another comparator treatment used in the study is **paclitaxel**, an **antimicrotubule agent**. This medication is administered intravenously, with the dosage also calculated in mg/m². The maximum treatment period for paclitaxel is 28 days. As with the other treatments, adherence to the dosing schedule is monitored to maintain the integrity of the trial data.
Efficacy
Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include **Progression-Free Survival (PFS)** and **Overall Survival (OS)**. PFS is defined as the time from the date of randomization until the date of objective progressive disease, as assessed by blinded independent central review (BICR) per RECIST v1.1, or death from any cause, whichever occurs first. OS is defined as the time from the date of randomization until death due to any cause.
Secondary endpoints include the **Objective Response Rate (ORR)**, which is the percentage of participants who achieve a complete response (CR) or partial response (PR) as the best overall response, confirmed at least 4 weeks after initial documentation of response, as assessed by BICR per RECIST v1.1. Other secondary endpoints involve changes 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 13, and the **Duration of Response (DOR)**, defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive progressive disease or death from any cause.
The trial will also evaluate the **Clinical Benefit Rate (CBR)**, which includes the percentage of participants with a best overall response of CR or PR confirmed at least 4 weeks after initial documentation of response or durable stable disease (SD) lasting at least 6 months from randomization to disease progression. Additionally, the incidence of treatment-emergent adverse events (TEAEs) and clinical laboratory abnormalities will be monitored. Efficacy assessments will be conducted at specified intervals throughout the trial, with data collection and analysis performed according to the trial protocol.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Willing and able to comply with the requirements and restrictions in this protocol.
- 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).
- 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
Exclusion Criteria
- Need for ongoing systemic anticancer therapies aside from the study treatment.
- 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.
- Requirement for ongoing therapy with any prohibited medications listed in Section 5.6.2.
- 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.
- 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.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 02 Dec 2024 | 3 |
 France | Not Recruiting | 02 Dec 2024 | 45 |
 Germany | Not Recruiting | 02 Dec 2024 | 11 |
 Greece | Not Recruiting | 02 Dec 2024 | 11 |
 Italy | Not Recruiting | 02 Dec 2024 | 67 |
 Poland | Not Recruiting | 02 Dec 2024 | 10 |
 Spain | Not Recruiting | 02 Dec 2024 | 32 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PACLITAXEL | Comparator | PHF00230MIG | INTRAVENOUS | 00 | 28 | SCP129816 |
Trodelvy 200 mg powder for concentrate for solution for infusion | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 00 | 21 | PRD9351384 |
Doxorubicin Teva 2 mg/ml Concentrate for Solution for Infusion | Comparator | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 00 | 21 | PRD490161 |