Clinical trial NCT03901339: Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Participants With HR+/HER2- Metastatic Breast Cancer
Official title: Phase 3 Study of Sacituzumab Govitecan (IMMU-132) Versus Treatment of Physician's Choice (TPC) in Subjects With Hormonal Receptor-Positive (HR+) Human Epidermal Growth Factor Receptor 2 (HER2) Negative Metastatic Breast Cancer (MBC) Who Have Failed at Least Two Prior Chemotherapy Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2019-04-03
Enrollment: 543
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to assess and compare the efficacy and safety of sacituzumab govitecan-hzi versus treatment of physician's choice (TPC) in participants with hormonal receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2-) negative metastatic breast cancer (MBC).


Eligibility criteria: Key Inclusion Criteria:

* Documented evidence of hormone receptor-positive human epidermal growth factor receptor 2 negative (HER2-negative) (hormonal receptor-positive (HR+)/HER2-) metastatic breast cancer (MBC) confirmed.
* Refractory to or relapsed after at least 2, and no more than 4, prior systemic chemotherapy regimens for metastatic disease:

  * At least 1 taxane in any setting.
  * At least 1 prior anticancer hormonal treatment in any setting.
  * At least 1 cyclin-dependent kinase inhibitor 4/6 in any setting.
* Eligible for one of the chemotherapy options listed in the TPC arm.
* Documented disease progression after the most recent therapy.
* Adequate bone marrow function (hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1,500 per mm\^3, platelets ≥ 100,000 per mm\^3).
* Adequate renal function: calculated creatinine clearance ≥ 30 mL/minute according to the Cockcroft and Gault formula .
* Adequate liver function (bilirubin ≤ 1.5 institutional upper limit of normal (IULN), or ≤ 3 IULN for individuals with documented Gilbert's syndrome, aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x IULN (in the case of liver metastases ≤ 5.0 x IULN)).
* Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta human chorionic gonadotropin (ß-hCG)).

Key Exclusion Criteria:

* Previous treatment with topoisomerase 1 Inhibitors as a free form or as other formulations.
* History of significant cardiovascular disease or clinically significant electrocardiogram (ECG) abnormality.
* Active serious infection requiring antibiotics.
* Any medical or other condition which, in the opinion of the Investigator, causes the individual to be medically unfit to receive sacituzumab govitecan or unsuitable for any reason.
* Locally advanced MBC (stage IIIc) in individuals who are candidates for curative intent therapy at the time of study enrollment.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) Assessment
timeFrame: Up to 42.8 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 42.8 months
measure: Objective Response Rate (ORR) by BICR and Local Investigator Review (LIR) Assessment
timeFrame: Up to 42.8 months
measure: Duration of Response (DOR) by BICR and LIR Assessment
timeFrame: Up to 42.8 months
measure: Clinical Benefit Rate (CBR) by BICR and LIR Assessment
timeFrame: Up to 42.8 months
measure: PFS by LIR Assessment
timeFrame: Up to 42.8 months
measure: Time to Deterioration (TTD) of Global Health Status/Quality of Life (QoL) Scale as Measured by European Organization for Research and Treatment of Cancer Quality of Life for Cancer Patients, Core Questionnaire Version 3.0 (EORTC QLQ-C30)
timeFrame: Up to 37.8 months
measure: TTD of Pain Score as Measured by EORTC QLQ-C30
timeFrame: Up to 37.8 months
measure: TTD of Fatigue Score as Measured by EORTC QLQ-C30
timeFrame: Up to 37.8 months
measure: Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 43.4 months
measure: Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Up to 43.4 months
measure: Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline
timeFrame: Up to 43.4 months
measure: Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) - Shift From Baseline Value to Best Value During Treatment
timeFrame: Up to 43.4 months
Other outcomes:
Locations:
city: Avondale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: La Jolla
country: United States
facility: University of California, San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles Hematology Oncology Medical Group
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine - Hematology/Oncology
state: California
city: Orange
country: United States
facility: University of California, Irvine Medical Center-Chao Family Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: Southern California Permanente Medical Group
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami - Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc.
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University - Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital, Inc.
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Mercy Medical Center, Medical Oncology & Hematology
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: Allina Health, Virginia Piper Cancer Institute
state: Minnesota
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center
state: Montana
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center/NYU Langone Health
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Germantown
country: United States
facility: The West Clinic, PC dba West Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center
state: Texas
city: Denton
country: United States
facility: Texas Oncology-Denton South
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital/Houston Methodist Cancer Center
state: Texas
city: Longview
country: United States
facility: Texas Oncology-Longview Cancer Center
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio - Mays Cancer Center
state: Texas
city: Arlington
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Salem
country: United States
facility: Oncology & Hematology Associates of Southwest Virginia, Inc. DBA Blue Ridge Cancer Care
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Brussels
country: Belgium
facility: Chirec Cancer Institute
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Namur
country: Belgium
facility: CHU UCL Namur/Site Sainte Elisabeth
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Montréal
country: Canada
facility: Centre Hospitalier de L'Universite de Montreal - Hôpital Notre-Dame
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke - Fleurimont
city: Ars-Laquenexy
country: France
facility: Hopital de Mercy
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Besançon
country: France
facility: Hôpital Jean-Minjoz
city: Dijon
country: France
facility: Centre Georges-Francois Leclerc
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier
country: France
facility: Institut Régional du Cancer de Montpellier
city: Paris
country: France
facility: Institut Curie
city: Pierre-Bénite
country: France
facility: Hospices Civils de Lyon
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Bonn
country: Germany
facility: Gynakologisches Zentrum Bonn
city: Bottrop
country: Germany
facility: Marienhospital Bottrop
city: Dessau
country: Germany
facility: Städtisches Klinikum Dessau
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Essen
country: Germany
facility: Kliniken Essen-Mitte
city: Frankfurt
country: Germany
facility: Centrum für Hämatologie und Onkologie Bethanien
city: Hamburg
country: Germany
facility: Onkologische Schwerpunktpraxis Eppendorf
city: Hannover
country: Germany
facility: Gynakologisch-Onkologische Praxis Hannover
city: Hannover
country: Germany
facility: DIAKOVERE Krankenhaus gGmbH Henriettenstift - Standort Kirchrode
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen - Heidelberg
city: Koblenz
country: Germany
facility: Praxisklinik für Hämatologie und Onkologie Koblenz
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromäerinnen
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Desio
country: Italy
facility: Ospedale di Desio
city: Lecce
country: Italy
facility: Ospedale Vito Fazzi di Lecce
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
city: Piacenza
country: Italy
facility: Azienda Unità Sanitaria Locale di Piacenza-Ospedale Guglielmo da Saliceto
city: Rome
country: Italy
facility: IFO Istituto Nazionale dei Tumori Regina Elena
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoekziekenhuis
city: Leidschendam
country: Netherlands
facility: Medisch Centrum Haaglanden Antoniushove
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruna
city: Barcelona
country: Spain
facility: Hospital Quirónsalud Barcelona Instituto Oncologico Baselga
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Castillón
country: Spain
facility: Hospital Provincial de Castellón
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Instituto Oncologico Bureau (IOB)
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Santiago De Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago de Compostela
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Cornwell
country: United Kingdom
facility: Royal Cornwall Hospital NHS Trust
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Rugo HS, Bardia A, Marme F, Cortes J, Schmid P, Loirat D, Tredan O, Ciruelos E, Dalenc F, Gomez Pardo P, Jhaveri KL, Delaney R, Valdez T, Wang H, Motwani M, Yoon OK, Verret W, Tolaney SM. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 Oct 21;402(10411):1423-1433. doi: 10.1016/S0140-6736(23)01245-X. Epub 2023 Aug 23.
citation: Rugo HS, Bardia A, Marme F, Cortes J, Schmid P, Loirat D, Tredan O, Ciruelos E, Dalenc F, Pardo PG, Jhaveri KL, Delaney R, Fu O, Lin L, Verret W, Tolaney SM. Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. J Clin Oncol. 2022 Oct 10;40(29):3365-3376. doi: 10.1200/JCO.22.01002. Epub 2022 Aug 26.
citation: Rugo HS, Bardia A, Tolaney SM, Arteaga C, Cortes J, Sohn J, Marme F, Hong Q, Delaney RJ, Hafeez A, Andre F, Schmid P. TROPiCS-02: A Phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2- metastatic breast cancer. Future Oncol. 2020 Apr;16(12):705-715. doi: 10.2217/fon-2020-0163. Epub 2020 Mar 30.
citation: Rugo HS, Schmid P, Tolaney SM, Dalenc F, Marme F, Shi L, Verret W, Shah A, Gharaibeh M, Bardia A, Cortes J. Health-related quality of life with sacituzumab govitecan in HR+/HER2- metastatic breast cancer in the phase III TROPiCS-02 trial. Oncologist. 2024 Sep 6;29(9):768-779. doi: 10.1093/oncolo/oyae088.
citation: Rugo HS, Bardia A, Marme F, Cortes J, Schmid P, Spears PA, Tolaney SM. A plain language summary of the TROPiCS-02 study in patients with breast cancer (HR-positive/HER2-negative). Future Oncol. 2024 Apr;20(11):635-651. doi: 10.2217/fon-2023-0845. Epub 2024 Jan 25.
citation: Rugo HS, Bardia A, Tolaney S. Sacituzumab govitecan for metastatic breast cancer: the TROPiCS-02 trial - Authors' reply. Lancet. 2024 Jul 27;404(10450):339-340. doi: 10.1016/S0140-6736(24)01049-3. No abstract available.
citation: McCann KE, Hurvitz SA. Innovations in targeted therapies for triple negative breast cancer. Curr Opin Obstet Gynecol. 2021 Feb 1;33(1):34-47. doi: 10.1097/GCO.0000000000000671.
citation: Kalinsky K, Diamond JR, Vahdat LT, Tolaney SM, Juric D, O'Shaughnessy J, Moroose RL, Mayer IA, Abramson VG, Goldenberg DM, Sharkey RM, Maliakal P, Hong Q, Goswami T, Wegener WA, Bardia A. Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol. 2020 Dec;31(12):1709-1718. doi: 10.1016/j.annonc.2020.09.004. Epub 2020 Sep 15.