| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Programmed cell death ligand 1 (PD-L1) negative metastatic triple-negative breast cancer or PD-L1-positive metastatic triple-negative breast cancer previously treated with an anti-PD-(L)1 agent in the curative setting. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Triple Negative Breast Cancer (breast cancer that does not have receptors for Oestrogen and Progesterone hormones or HER2 proteins). |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10084066 |
| E.1.2 | Term | Triple negative breast cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare progression-free survival (PFS) as assessed by BICR between sacituzumab govitecan versus treatment of physician’s choice. |
|
| E.2.2 | Secondary objectives of the trial |
-To compare overall survival between the 2 arms
-To compare objective response rate as assessed by blinded independent central review (BICR) between the 2 arms
-To compare duration of response as assessed by BICR between the 2 arms
-To compare time to onset of response as assessed by BICR between the 2 arms
-To compare safety and tolerability between the 2 arms
-To compare mean change from baseline in the physical functioning domain and time to deterioration (TTD) in fatigue as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Questionnaire, Version 3.0 (EORTC QLQ-C30) between the 2 arms |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria to be eligible for participation in this study (no waivers for patient eligibility will be offered or permitted):
1) Female or male patients, regardless of race and ethnic group, who are 18 years of age or older, able to understand and give written informed consent.
2) Patients with locally advanced, inoperable, or metastatic TNBC who have not received previous systemic therapy for advanced disease and whose tumors are PD-L1 negative at screening. Alternatively, patients whose tumors are PD-L1 positive at screening will be eligible if they received an anti-programmed death (ligand) 1 (anti-PD-[L]1) agent (ie, checkpoint inhibitor) in the adjuvant or neoadjuvant setting or if they cannot be treated with an anti-PD-(L)1 agent due to a comorbidity.
3) Have provided representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in blocks (preferred) or have at least 20 to 25 freshly sectioned unstained slides from fresh biopsy tissue (preferred) or archival tissue block for central testing of ER, progesterone receptor, HER2, and PD-L1 and additional biomarker testing. A baseline biopsy is required if archival tissue is not available and this procedure must be performed prior to the first dose of study treatment and after the patient provides written informed consent. Fine needle aspirates and bone biopsies are not suitable samples. A discussion with the medical monitor is required if only 15 to 19 unstained slides are available and it is not clinically feasible to obtain a new biopsy.
4) ECOG performance status score of 0 or 1
5) Life expectancy ≥ 3 months
6) Recovered from major surgery for ≥ 2 weeks
7) Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study treatment initiation (hemoglobin ≥ 9 g/dL, ANC ≥ 1500/mm3, and platelets ≥ 100,000/μL).
8) Adequate hepatic function (bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if known liver metastases, and serum albumin > 3 g/dL).
9) Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation.
10) International Normalized Ratio (INR)/PT and PTT or aPTT ≤ 1.5 ULN unless patient is currently receiving therapeutic anticoagulant therapy.
11) Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in protocol Appendix 3.
12) Patients with HIV must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/ disease |
|
| E.4 | Principal exclusion criteria |
Patients who meet any of the following exclusion criteria are not eligible to be enrolled in this study (no waivers for patient eligibility will be offered or permitted):
1) Positive serum pregnancy test or women who are lactating.
2) Known or severe (≥ Grade 3) hypersensitivity or allergy to sacituzumab govitecan and/or the chemotherapy regimen of choice in the TPC arm (eg, nab-paclitaxel, paclitaxel, gemcitabine, or Carboplatin), their metabolites, or formulation excipient.
3) Requirement for ongoing therapy with or prior use of any prohibited medications listed in section 5.6.1 of the protocol.
4) Patients may not have received systemic anticancer treatment (with the exception of endocrine therapy) within the previous 6 months or radiation therapy within 2 weeks prior to enrollment. Patients must have recovered (ie, > Grade 2 is considered not recovered) from AEs due to a previously administered agent at the time of study entry.
- Note: patients with any grade neuropathy or alopecia are an exception to this criterion and will qualify for the study.
- Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
5) Patients may not be participating in a study with an investigational agent or investigational device within 4 weeks prior to randomization. Patients participating in observational studies are eligible.
6) Have previously received topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor.
7) Have an active second malignancy.
8) Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate (with the exception of those treated with chemotherapy) provided they have stable CNS disease (defined as radiographic stability demonstrated with a minimum of 2 posttreatment brain imaging assessments; one performed during screening) for at least 4 weeks prior to enrollment and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and have also been clinically stable for at least 2 weeks while taking ≤ 10 mg/day of prednisone or its equivalent. All patients with carcinomatous meningitis are excluded regardless of clinical stability.
9) Met any of the following criteria for cardiac disease:
a) Myocardial infarction or unstable angina pectoris within 6 months of enrollment.
b) 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.
c) New York Heart Association Class III or greater congestive heart failure or known left ventricular ejection fraction of < 40%.
10) Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or GI perforation within 6 months of enrollment.
11) Have active serious infection requiring antibiotics.
12) Patients positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
13) Have active HBV (defined as having a positive HBsAg test) or HCV.
14) 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.
15) Has received a live vaccine within 30 days prior to randomization. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-free survival (PFS) , time from the date of randomization until the date of objective progressive disease (PD), as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, or death (whichever comes first). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Monitored throughout the study. |
|
| E.5.2 | Secondary end point(s) |
- Overall survival (OS) is defined as the time from the date of randomization until death due to any cause.
- objective response rate (ORR) is defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks after initial documentation of response as assessed by BICR per RECIST Version 1.1.
- Duration of response (DOR) is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive PD or death from any cause (whichever comes first) as assessed by BICR per RECIST Version 1.1.
- Time to onset of response (TTR) is defined as the time from the date of randomization until the first documentation of CR or PR as assessed by BICR per RECIST Version 1.1.
- Incidence of treatment-emergent AEs (TEAEs) and clinical laboratory abnormalities.
- Time to deterioration (TTD) of global health status/quality of life (QOL), pain, and fatigue subscale domains of the EORTC QLQ-C30 at Week 25.
- TTD of fatigue domain of the EORTC QLQ-C30 is defined as the time between the date of randomization and the date of assessment at which a patient experienced a deterioration (ie, ≥ 10 points worsening from baseline in the fatigue domain) or death. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Monitored throughout the study. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 107 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Chile |
| Peru |
| Switzerland |
| Puerto Rico |
| Australia |
| Brazil |
| Canada |
| Israel |
| Japan |
| Mexico |
| South Africa |
| Turkey |
| United Kingdom |
| United States |
| Austria |
| Belgium |
| Czechia |
| France |
| Germany |
| Hungary |
| Italy |
| Netherlands |
| Poland |
| Romania |
| Slovakia |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study will be the date of the last visit/contact/survival follow-up in the study.
All Patients:
The end of the entire study for all patients is defined as the date on which the last patient remaining on study completes the last study visit/call or when the sponsor decides to end the study. The sponsor reserves the right to terminate the study at any time for any reason (including safety). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
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