Asian Study of Sacituzumab Govitecan (IMMU-132) in HR+/HER2- Metastatic Breast Cancer (MBC)

A Phase 3 Asian 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 Negative (HER2-) Metastatic Breast Cancer (MBC) Who Have Failed at Least 2 Prior Chemotherapy Regimens

The goal of this study is to compare the study drug, sacituzumab govitecan-hziy, versus doctors' treatment of choice in participants with HR+/HER2- metastatic breast cancer (MBC) who have failed at least 2 prior chemotherapy regimens.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Eribulin Mesylate Injection; Drug: Capecitabine Oral Product; Drug: Gemcitabine Injection; Drug: Vinorelbine injection; Drug: Sacituzumab Govitecan-hziy

Detailed Description

Approximately 330 eligible participants will be randomly allocated to one of the following 2 treatment arms in a 1:1 ratio:

Investigational Arm:

Sacituzumab Govitecan-hziy 10 mg/kg via intravenous (IV) injection administered on Day 1 and Day 8 (21-day cycle).

Control Arm:

Recommended doses and schedules as per package insert depending on region. Eribulin; Capecitabine; Gemcitabine; Vinorelbine Participants will be treated until disease progression as judged by local investigator review, development of unacceptable toxicity, or withdrawal of consent.

• Study Type: Interventional
• Enrollment (Actual): 331
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Chinese PLA General Hospital
  • Beijing, China
    • Peking University People's Hospital
  • Beijing, China
    • Cancer Hospital Chinese Academy of Medical Science
  • Changchun, China
    • Jilin cancer hospital
  • Changchun, China
    • The First Hospital of Jilin University
  • Chengdu, China
    • West China Hospital, Sichuan University
  • Chengdu, China
    • Chongqing University Cancer Hospital
  • Fuzhou, China
    • Fujian Medical University Union Hospital
  • Guangzhou, China
    • Guangdong Provincial People's Hospital
  • Guangzhou, China
    • Sun Yat-sen University Cancer Center
  • Guangzhou, China
    • Sun Yat Sen Memorial Hospital of Sun Yat sen University
  • Hangzhou, China
    • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
  • Hangzhou, China
    • Zhejiang Cancer Hospital
  • Hefei, China
    • Anhui Provincial Hospital
  • Hefei, China
    • The Second Hospital of Anhui Medical University
  • Jinan, China
    • Shandong Cancer Hospital
  • Kunming, China
    • Yunnan Cancer Hospital
  • Linyi, China
    • Linyi Cancer Hospital
  • Nanjing, China
    • Jiangsu Province Hospital
  • Nanjing, China
    • Nanjing Drum Tower Hospital
  • Shanghai, China
    • Shanghai General Hospital
  • Tianjin, China
    • Tianjin Medical University Cancer Institute & Hospital
  • Wuhan, China
    • Hubei Cancer Hospital
  • Wuhan, China
    • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Xi'an, China
    • The First Affiliated Hospital of Xi'an Jiaotong University
  • Zhengzhou, China
    • Henan Cancer Hospital
  • Ürümqi, China
    • Affiliated Tumor Hospital of Xinjiang Medical University
• Korea, Republic of
  • Busan, Korea, Republic of
    • Dong-A University Hospital
  • Seongnam, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital Yonsei University Health System
  • Suwon, Korea, Republic of
    • Ajou University Hospital
• Taiwan
  • Changhua, Taiwan
    • Changhua Christian Medical Foundation Changhua Christian Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan
    • Chang Gung Memorial Hospital, Linkou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Female or male individuals aged ≥18 years at the time of signing the informed consent form
• Documented evidence of hormone receptor-positive HER2-negative (HR+/HER2-) MBC confirmed
• Refractory to or relapsed after at least 2, and no more than 4, prior systemic chemotherapy regimens for MBC
• Should have been previously treated with at least 1 taxane in any setting, at least 1 prior anticancer hormonal treatment in any setting
• Eligible for one of the chemotherapy options listed in the TPC arm
• Documented radiographic disease progression after the most recent therapy
• Measurable disease by CT or MRI in accordance with RECIST v 1.1, bone-only disease is not measurable and is not permitted.
• Adequate bone marrow function, hepatic and renal function
• 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
• Individuals who have known brain metastases.
• Have an active second malignancy within 3 years prior to providing informed consent
• Individuals with active hepatitis B virus (HBV), or hepatitis C virus infection (measurable viral RNA load with polymerase chain reaction).
• Active serious infection requiring systemic antibiotic use within 7 days before Cycle1 Day 1.
• 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.
• Known hypersensitivity or intolerance to either of the study treatments or any of the excipients.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sacituzumab Govitecan-hziy; Participants will receive Sacituzumab Govitecan-hziy 10 mg/kg on Days 1 and 8 of a 21-day cycle.	Drug: Sacituzumab Govitecan-hziy; Sacituzumab govitecan 10 mg/kg via IV injection administered on Days 1 and 8 of a 21-day cycle. Subjects will continue to receive study treatment until PD as judged by local investigator review, development of unacceptable toxicity, or withdrawal of consent.; Other Names: IMMU-132; GS-0132; Trodelvy™
Active Comparator: Treatment of Physician's Choice (TPC); Participants will receive recommended doses and schedules as per package insert depending on region.; Eribulin (1.4 mg/m^2 of eribulin mesylate or 1.23 mg/m^2 of eribulin on Days 1 and 8 of a 21-day cycle); Capecitabine (1000 to 1250 mg/m^2 twice daily on Days 1 to 14 of a 21-day cycle); Gemcitabine (800 to 1200 mg/m^2 on Days 1, 8, and 15 of a 28-day cycle); Vinorelbine (25 mg/m^2 on Day 1 weekly)	Drug: Eribulin Mesylate Injection; Eribulin is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts.; Other Names: Halaven; Drug: Capecitabine Oral Product; Capecitabine is administered orally (PO) following recommended doses and regimens as per approved package inserts.; Other Names: Xeloda; Drug: Gemcitabine Injection; Gemcitabine is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts.; Other Names: Gemzar; Drug: Vinorelbine injection; Vinorelbine is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts.; Other Names: Navelbine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS is defined as from the date of randomization until the date of disease progression (PD) or death, whichever occurs earlier. Disease progression will be determined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) by Independent Reviewing Committee (IRC).	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0		First dose date up to 4 years plus 30 days
Percentage of Participants Experiencing Serious Adverse Events (SAEs) According to NCI CTCAE Version 5.0		First dose date up to 4 years plus 30 days
Pharmacokinetic (PK) Parameter: Cmax of Sacituzumab Govitecan-hziy and Free SN-38	Cmax is defined as the maximum observed concentration of drug.	Up to 4 years
PK Parameter: Ctrough of Sacituzumab Govitecan-hziy and Free SN-38	Ctrough is defined as the concentration of drug at the end of the dosing interval.	Up to 4 years
Overall Survival (OS)	OS is defined as from the date of randomization to death from any cause.	Up to 4 years
Objective Response Rate (ORR) by IRC	ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR).	Up to 4 years
Duration of Response (DOR) by IRC	DOR is defined as from the date of first onset of tumor response (CR or PR) to PD or death, whichever occurs earlier.	Up to 4 years
Clinical Benefit Rate (CBR) by IRC	CBR is defined as best overall response of CR or PR or durable stable disease (SD) (duration of SD ≥ 6 months after randomization).	Up to 4 years
Change From Baseline of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30, Version 3.0 (EORTC QLQ-C30) Score	The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) to assess 15 scales; 1 global health status/quality of life (QOL), 5 functional scales (physical, role, cognitive, emotional, and social), and 9 symptom/item scales(fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of function, a high score for the global health status/QOL represents a high QOL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.	Baseline, up to 4 years
Change From Baseline of the European Quality of Life 5-Dimensions 5 Levels Instrument (EuroQOL EQ-5D-5L) Score	The EQ-5D-5L is an instrument for use as a measure of health outcome.The EQ-5D-5L consists of 2 sections: the EuroQoL (5 dimensions) (EQ-5D) descriptive system and the EuroQoL visual analogue scale (EQ-VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ-VAS indicate better health.	Baseline, up to 4 years
Percentage of Participants Experiencing Treatment-Emergent Adverse Events Assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE)	NCI PRO-CTCAE is a patient-reported item library used to evaluate symptomatic treatment-emergent adverse events in participants on cancer clinical trials. The items selected for this study include: decreased appetite, nausea, vomiting, constipation, diarrhea, abdominal pain, shortness of breath, hair loss, and fatigue.	Baseline, up to 4 years
PK Parameter: Tmax of of Sacituzumab Govitecan-hziy and Free SN-38	Tmax is defined as the time to maximum drug concentration.	Up to 4 years

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Parexel; Iqvia Pty Ltd; Medidata Solutions
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Kwapisz D. Sacituzumab Govitecan-hziy in Breast Cancer. Am J Clin Oncol. 2022 Jul 1;45(7):279-285. doi: 10.1097/COC.0000000000000919. Epub 2022 May 12.

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2020
• Primary Completion (Actual): April 30, 2023
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: November 17, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Antibody Drug Conjugate; IMMU-132; sacituzumab govitecan; Unresectable or Metastatic Breast Cancer; hormonal receptor; HR positive; Anti-TROP2; Human epidermal growth factor receptor 2 (HER2) Negative
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Immunoconjugates; Capecitabine; Vinorelbine; Gemcitabine; Sacituzumab govitecan
• Other Study ID Numbers: EVER-132-002; CTR20210096 (Registry Identifier: China: Drug Clinical Trial Registration and Information Disclosure Platform)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No