Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Participants With HR+/HER2- Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

— TROPiCS-02  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03901339
• Other study ID #: IMMU-132-09
• Secondary ID: 2018-004201-33
• Status: Completed
• Phase: Phase 3
• Start date: May 8, 2019
• Est. completion date: October 20, 2023

Study information

• Verified date: November 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 543
• Est. completion date: October 20, 2023
• Est. primary completion date: October 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Sacituzumab Govitecan-hziy
Administered intravenously
• Eribulin
Administered intravenously per NCCN guidelines
• Capecitabine
Administered orally per NCCN guidelines
• Gemcitabine
Administered intravenously per NCCN guidelines
• Vinorelbine
Administered intravenously per NCCN guidelines

Locations

Country	Name	City	State
Belgium	Chirec Cancer Institute	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Leuven	Leuven
Belgium	CHU UCL Namur/Site Sainte Elisabeth	Namur
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Centre Hospitalier de L'Universite de Montreal - Hôpital Notre-Dame	Montréal
Canada	Centre Hospitalier Universitaire de Sherbrooke - Fleurimont	Sherbrooke
France	Hopital de Mercy	Ars-Laquenexy
France	Institut Sainte Catherine	Avignon
France	Hôpital Jean-Minjoz	Besançon
France	Centre Georges-Francois Leclerc	Dijon
France	Centre Leon Berard	Lyon
France	Institut Régional du Cancer de Montpellier	Montpellier
France	Institut Curie	Paris
France	Hospices Civils de Lyon	Pierre-Bénite
France	Institut de Cancérologie Lucien Neuwirth	Saint-Priest-en-Jarez
France	Institut Claudius Regaud	Toulouse
Germany	HELIOS Klinikum Berlin-Buch	Berlin
Germany	Gynakologisches Zentrum Bonn	Bonn
Germany	Marienhospital Bottrop	Bottrop
Germany	Städtisches Klinikum Dessau	Dessau
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Kliniken Essen-Mitte	Essen
Germany	Centrum für Hämatologie und Onkologie Bethanien	Frankfurt
Germany	Onkologische Schwerpunktpraxis Eppendorf	Hamburg
Germany	DIAKOVERE Krankenhaus gGmbH Henriettenstift - Standort Kirchrode	Hannover
Germany	Gynakologisch-Onkologische Praxis Hannover	Hannover
Germany	Nationales Centrum für Tumorerkrankungen - Heidelberg	Heidelberg
Germany	Praxisklinik für Hämatologie und Onkologie Koblenz	Koblenz
Germany	Universitätsmedizin Mannheim	Mannheim
Germany	Klinikum Mutterhaus der Borromäerinnen	Trier
Italy	Azienda Ospedaliera Spedali Civili di Brescia	Brescia
Italy	Ospedale di Desio	Desio
Italy	Ospedale Vito Fazzi di Lecce	Lecce
Italy	Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera San Gerardo di Monza	Monza
Italy	Azienda Unità Sanitaria Locale di Piacenza-Ospedale Guglielmo da Saliceto	Piacenza
Italy	IFO Istituto Nazionale dei Tumori Regina Elena	Rome
Netherlands	Antoni van Leeuwenhoekziekenhuis	Amsterdam
Netherlands	Medisch Centrum Haaglanden Antoniushove	Leidschendam
Netherlands	Maastricht UMC+	Maastricht
Spain	Complejo Hospitalario Universitario A Coruna	A Coruña
Spain	Hospital de la Santa Creu I Sant Pau	Barcelona
Spain	Hospital Quirónsalud Barcelona Instituto Oncologico Baselga	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Provincial de Castellón	Castillón
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Instituto Oncologico Bureau (IOB)	Madrid
Spain	Hospital Clinico Universitario de Santiago de Compostela	Santiago De Compostela
Spain	Hospital Universitario Virgen del Rocio	Sevilla
United Kingdom	Royal Cornwall Hospital NHS Trust	Cornwell
United Kingdom	Royal Surrey County Hospital	Guildford
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Barts Health NHS Trust	London
United Kingdom	The Royal Marsden NHS Foundation Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Virginia Cancer Specialists	Arlington	Virginia
United States	Emory University - Winship Cancer Institute	Atlanta	Georgia
United States	Northside Hospital, Inc.	Atlanta	Georgia
United States	Rocky Mountain Cancer Centers	Aurora	Colorado
United States	University of Colorado	Aurora	Colorado
United States	HonorHealth Research Institute	Avondale	Arizona
United States	Mercy Medical Center, Medical Oncology & Hematology	Baltimore	Maryland
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center	Dallas	Texas
United States	Texas Oncology-Denton South	Denton	Texas
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Summit Medical Group	Florham Park	New Jersey
United States	The West Clinic, PC dba West Cancer Center	Germantown	Tennessee
United States	Houston Methodist Hospital/Houston Methodist Cancer Center	Houston	Texas
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	University of California, San Diego Moores Cancer Center	La Jolla	California
United States	Texas Oncology-Longview Cancer Center	Longview	Texas
United States	Los Angeles Hematology Oncology Medical Group	Los Angeles	California
United States	UCLA Department of Medicine - Hematology/Oncology	Los Angeles	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	Miami Cancer Institute	Miami	Florida
United States	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Allina Health, Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University Cancer Center	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Laura and Isaac Perlmutter Cancer Center/NYU Langone Health	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	University of California, Irvine Medical Center-Chao Family Comprehensive Cancer Center	Orange	California
United States	Orlando Health, Inc.	Orlando	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania
United States	Maryland Oncology Hematology, P.A.	Rockville	Maryland
United States	Washington University School of Medicine - Siteman Cancer Center	Saint Louis	Missouri
United States	Oncology & Hematology Associates of Southwest Virginia, Inc. DBA Blue Ridge Cancer Care	Salem	Virginia
United States	UT Health San Antonio - Mays Cancer Center	San Antonio	Texas
United States	Southern California Permanente Medical Group	San Diego	California
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Arizona Oncology Associates, PC	Tucson	Arizona
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	The University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

References & Publications (15)

Bardia A, Mayer IA, Diamond JR, Moroose RL, Isakoff SJ, Starodub AN, Shah NC, O'Shaughnessy J, Kalinsky K, Guarino M, Abramson V, Juric D, Tolaney SM, Berlin J, Messersmith WA, Ocean AJ, Wegener WA, Maliakal P, Sharkey RM, Govindan SV, Goldenberg DM, Vahdat LT. Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2017 Jul 1;35(19):2141-2148. doi: 10.1200/JCO.2016.70.8297. Epub 2017 Mar 14. — View Citation

Burki TK. Sacituzumab govitecan activity in advanced breast cancer. Lancet Oncol. 2017 May;18(5):e246. doi: 10.1016/S1470-2045(17)30232-2. Epub 2017 Mar 23. No abstract available. — View Citation

Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Arrojo R, Liu D, Rossi EA, Chang CH, Goldenberg DM. Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. Bioconjug Chem. 2015 May 20;26(5):919-31. doi: 10.1021/acs.bioconjchem.5b00223. Epub 2015 May 8. — View Citation

Cardillo TM, Sharkey RM, Rossi DL, Arrojo R, Mostafa AA, Goldenberg DM. Synthetic Lethality Exploitation by an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2-wild-type Triple-Negative Breast Cancer. Clin Cancer Res. 2017 Jul 1;23(13):3405-3415. doi: 10.1158/1078-0432.CCR-16-2401. Epub 2017 Jan 9. — View Citation

Chang CH, Wang Y, Zalath M, Liu D, Cardillo TM, Goldenberg DM. Combining ABCG2 Inhibitors with IMMU-132, an Anti-Trop-2 Antibody Conjugate of SN-38, Overcomes Resistance to SN-38 in Breast and Gastric Cancers. Mol Cancer Ther. 2016 Aug;15(8):1910-9. doi: 10.1158/1535-7163.MCT-16-0219. Epub 2016 May 20. — View Citation

Faltas B, Goldenberg DM, Ocean AJ, Govindan SV, Wilhelm F, Sharkey RM, Hajdenberg J, Hodes G, Nanus DM, Tagawa ST. Sacituzumab Govitecan, a Novel Antibody--Drug Conjugate, in Patients With Metastatic Platinum-Resistant Urothelial Carcinoma. Clin Genitourin Cancer. 2016 Feb;14(1):e75-9. doi: 10.1016/j.clgc.2015.10.002. Epub 2015 Oct 19. — View Citation

Goldenberg DM, Cardillo TM, Govindan SV, Rossi EA, Sharkey RM. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget. 2015 Sep 8;6(26):22496-512. doi: 10.18632/oncotarget.4318. Erratum In: Oncotarget. 2020 Mar 10;11(10):942. — View Citation

Goldenberg DM, Stein R, Sharkey RM. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget. 2018 Jun 22;9(48):28989-29006. doi: 10.18632/oncotarget.25615. eCollection 2018 Jun 22. — View Citation

Gray JE, Heist RS, Starodub AN, Camidge DR, Kio EA, Masters GA, Purcell WT, Guarino MJ, Misleh J, Schneider CJ, Schneider BJ, Ocean A, Johnson T, Gandhi L, Kalinsky K, Scheff R, Messersmith WA, Govindan SV, Maliakal PP, Mudenda B, Wegener WA, Sharkey RM, Goldenberg DM. Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Clin Cancer Res. 2017 Oct 1;23(19):5711-5719. doi: 10.1158/1078-0432.CCR-17-0933. Epub 2017 Jul 5. — View Citation

Han C, Bellone S, Schwartz PE, Govindan SV, Sharkey RM, Goldenberg DM, Santin AD. Sacituzumab Govitecan (IMMU-132) in treatment-resistant uterine serous carcinoma: A case report. Gynecol Oncol Rep. 2018 May 23;25:37-40. doi: 10.1016/j.gore.2018.05.009. eCollection 2018 Aug. — View Citation

Ocean AJ, Starodub AN, Bardia A, Vahdat LT, Isakoff SJ, Guarino M, Messersmith WA, Picozzi VJ, Mayer IA, Wegener WA, Maliakal P, Govindan SV, Sharkey RM, Goldenberg DM. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Cancer. 2017 Oct 1;123(19):3843-3854. doi: 10.1002/cncr.30789. Epub 2017 May 30. — View Citation

Sahota S, Vahdat LT. Sacituzumab govitecan: an antibody-drug conjugate. Expert Opin Biol Ther. 2017 Aug;17(8):1027-1031. doi: 10.1080/14712598.2017.1331214. Epub 2017 May 22. — View Citation

Sharkey RM, McBride WJ, Cardillo TM, Govindan SV, Wang Y, Rossi EA, Chang CH, Goldenberg DM. Enhanced Delivery of SN-38 to Human Tumor Xenografts with an Anti-Trop-2-SN-38 Antibody Conjugate (Sacituzumab Govitecan). Clin Cancer Res. 2015 Nov 15;21(22):5131-8. doi: 10.1158/1078-0432.CCR-15-0670. Epub 2015 Jun 23. — View Citation

Starodub AN, Ocean AJ, Shah MA, Guarino MJ, Picozzi VJ Jr, Vahdat LT, Thomas SS, Govindan SV, Maliakal PP, Wegener WA, Hamburger SA, Sharkey RM, Goldenberg DM. First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Clin Cancer Res. 2015 Sep 1;21(17):3870-8. doi: 10.1158/1078-0432.CCR-14-3321. Epub 2015 May 5. — View Citation

Vlachostergios PJ, Jakubowski CD, Niaz MJ, Lee A, Thomas C, Hackett AL, Patel P, Rashid N, Tagawa ST. Antibody-Drug Conjugates in Bladder Cancer. Bladder Cancer. 2018 Jul 30;4(3):247-259. doi: 10.3233/BLC-180169. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	PFS is defined as the time from the date of randomization to the date of the first documentation of disease progression or death (whichever occurs first) according to blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).	Up to approximately 3 years
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of participants who have a best overall response of either Complete Remission (CR) or Partial Response (PR) that is confirmed = 4 weeks later according to BICR using RECIST 1.1.	Up to approximately 3 years
Secondary	Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death from any cause.	Up to approximately 5 years
Secondary	Duration of Response (DOR)	DOR is defined as the time from the date a response was first documented until the date of the first documentation of disease progression or date of death (whichever occurs first).	Up to approximately 3 years
Secondary	Clinical Benefit Rate (CBR)	CBR is defined as best overall response of CR or PR or durable stable disease (duration of SD = 6 months after randomization).	Up to approximately 3 years
Secondary	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)	The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant).; Deterioration is defined as greater than or equal to 10 points worsening from baseline in the global health status/QoL scale.	Up to approximately 3 years
Secondary	TTD of Pain Score as Measured by EORTC QLQ-C30	The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant).; Deterioration is defined as greater than or equal to 10 points worsening from baseline in the pain score.	Up to approximately 3 years
Secondary	TTD of Fatigue Score as Measured by EORTC QLQ-C30	The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant).; Deterioration is defined as greater than or equal to 10 points worsening from baseline in the fatigue score.	Up to approximately 3 years
Secondary	Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)		Up to approximately 3 years
Secondary	Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs)		Up to approximately 3 years
Secondary	Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities		Up to approximately 3 years
Secondary	Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status		Baseline, Up to approximately 3 years

External Links

•   Gilead Clinical Trials Website