NCT03901339 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2024-10-21

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).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) Assessment

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Objective Response Rate (ORR) by BICR and Local Investigator Review (LIR) Assessment

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outcome · POSTED

Duration of Response (DOR) by BICR and LIR Assessment

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outcome · POSTED

Clinical Benefit Rate (CBR) by BICR and LIR Assessment

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outcome · POSTED

PFS by LIR Assessment

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outcome · POSTED

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)

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outcome · POSTED

TTD of Pain Score as Measured by EORTC QLQ-C30

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outcome · POSTED

TTD of Fatigue Score as Measured by EORTC QLQ-C30

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outcome · POSTED

Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)

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outcome · POSTED

Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (TESAEs)

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outcome · POSTED

Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline

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outcome · POSTED

Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) - Shift From Baseline Value to Best Value During Treatment

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants will receive sacituzumab govitecan-hziy 10 mg/kg via intravenous (IV) injection administered on Day 1 and Day 8 of a 21-day cycle.
intervention Names
Drug: Sacituzumab Govitecan-hziy
label
Sacituzumab Govitecan-hziy
type
EXPERIMENTAL
description
Participants will receive TPC determined prior to randomization from one of the following single-agent treatment: Dosing per National Comprehensive Cancer Network (NCCN) guidelines (with dose modifications for if toxic) * Eribulin: 1.4 mg/m\^2 for North American sites, 1.23 mg/m\^2 for European sites) via IV on Days 1 and 8 of a 21-day cycle * Capecitabine: 1000-1250 mg/m\^2 orally twice daily for 2 weeks followed by a 1-week rest period given as a 21-day cycle * Gemcitabine: 800-1200 mg/m\^2 via IV on Days 1, 8, and 15 of each 28-day cycle or per institution * Vinorelbine: 25 mg/m\^2 via IV on Day 1 weekly cycle per institution
intervention Names
Drug: Eribulin
Drug: Capecitabine
Drug: Gemcitabine
Drug: Vinorelbine
label
Treatment of Physician's Choice (TPC)
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Sacituzumab Govitecan-hziy
description
Administered intravenously
name
Sacituzumab Govitecan-hziy
other Names
IMMU-132
GS-0132
type
DRUG
arm Group Labels
Treatment of Physician's Choice (TPC)
description
Administered intravenously per NCCN guidelines
name
Eribulin
type
DRUG
arm Group Labels
Treatment of Physician's Choice (TPC)
description
Administered orally per NCCN guidelines
name
Capecitabine
type
DRUG
arm Group Labels
Treatment of Physician's Choice (TPC)
description
Administered intravenously per NCCN guidelines
name
Gemcitabine
type
DRUG
arm Group Labels
Treatment of Physician's Choice (TPC)
description
Administered intravenously per NCCN guidelines
name
Vinorelbine
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 543
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
PFS was defined as the time from the date of randomization to the date of the first documentation of disease progression or death (whichever occurred first) according to BICR using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Disease progression was defined as an increase of greater than 20% in the sum of the longest diameter (LD) of target lesions and a 5 mm absolute increase, taking as a reference the smallest sum LD recorded since the baseline assessment or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate.
measure
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) Assessment
time Frame
Up to 42.8 months

secondary Outcomes

description
OS was defined as the time from the date of randomization to the date of death from any cause. OS was estimated using Kaplan-Meier estimate. Participants without documentation of death were censored on the date they were last known to be alive.
measure
Overall Survival (OS)
time Frame
Up to 42.8 months
description
ORR was defined as the percentage of participants who had the best overall response of either complete response (CR) or partial response (PR) that was confirmed at 4 weeks or later after initial response by BICR and LIR using RECIST 1.1. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.
measure
Objective Response Rate (ORR) by BICR and Local Investigator Review (LIR) Assessment
time Frame
Up to 42.8 months
description
DOR was defined as the time from the date a response of CR or PR was first documented until the date of the first documentation of disease progression or date of death (whichever occurred first). DOR was analyzed based on both BICR and LIR assessments. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Disease progression was defined as an increase of greater than 20% in the sum of the LD of target lesions and a 5 mm absolute increase, taking as a reference the smallest sum LD recorded since the baseline assessment or the appearance of new non-target lesions. DOR was estimated using Kaplan-Meier estimate.
measure
Duration of Response (DOR) by BICR and LIR Assessment
time Frame
Up to 42.8 months
description
CBR was defined as the percentage of participants with the best overall response of CR, PR, or durable stable disease (duration of SD ≥ 6 months after randomization). CBR was analyzed based on both BICR and LIR assessments. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD: Disease progression was defined as an increase of greater than 20% in the sum of the LD of target lesions and a 5 mm absolute increase, taking as a reference the smallest sum LD recorded since the baseline assessment or the appearance of new non-target lesions.
measure
Clinical Benefit Rate (CBR) by BICR and LIR Assessment
time Frame
Up to 42.8 months
description
PFS was defined as the time from the date of randomization to the date of the first documentation of disease progression or death (whichever occurred first) according to LIR using RECIST 1.1. Disease progression was defined as an increase of greater than 20% in the sum of the LD of target lesions and a 5 mm absolute increase, taking as a reference the smallest sum LD recorded since the baseline assessment or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate.
measure
PFS by LIR Assessment
time Frame
Up to 42.8 months
description
TTD was defined as the time from randomization to the first date a subject achieves 10-point deterioration from baseline in the global health status/QoL scale.The EORTC QLQ-C30 is a 30-item questionnaire to assess QoL of cancer patients. It has 5 functional scales(physical,role,emotional,cognitive, social)1 global health status scale,3 symptom scales (fatigue, nausea and vomiting, pain),and 6 single items(dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial difficulties). Participant responses to global health status,'How would you rate your overall health during the past week?' (Item 29)and the QoL 'How would you rate your overall quality of life during the past week?'(Item 30)questions were scored on 7-point scale (1=very poor; 7=excellent). All scales and single-item measures range in score from 0 to 100. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100. Higher scores for GHS show a better level of functioning.
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)
time Frame
Up to 37.8 months
description
TTD was defined as the time from randomization to the first date a subject achieves 10-point deterioration from baseline in the pain score.The EORTC QLQ-C30 is a questionnaire to assess quality of life, it is composed of 30 questions(items) resulting in 5 functional scales(physical, role, emotional, cognitive, social),1 global health status scale,3 symptom scales (fatigue, nausea and vomiting, pain),and 6 single items(dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial difficulties). All of the scales and single-item measures range in score from 0 to 100. Participant responses to 2 questions about pain, 'Have you had pain' and 'Did pain interfere with your daily activities' were scored on 4-point scale (1=not at all;4=very much). Summed raw scores were standardized by linear transformation so that scores ranges from 0 to 100. Higher scores on the symptom scales indicate a higher level of symptoms (i.e. a worse state of the participant).
measure
TTD of Pain Score as Measured by EORTC QLQ-C30
time Frame
Up to 37.8 months
description
TTD was defined as the time from randomization to the first date a subject achieves 10-point deterioration from baseline in the fatigue score.The EORTC QLQ-C30 is a questionnaire to assess quality of life, it is composed of 30 questions(items) resulting in 5 functional scales(physical, role, emotional, cognitive, social),1 global health status scale,3 symptom scales (fatigue, nausea and vomiting, pain),and 6 single items(dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial difficulties).All of the scales and single-item measures range in score from 0 to 100.Participant responses to 3 questions about fatigue 'Did you need to rest', 'Have you felt weak' and 'Were you tired' were scored on a 4-point scale (1=not at all;4=very much).Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100. Higher scores on the symptom scales indicate a higher level of symptoms (i.e. a worse state of the participant).
measure
TTD of Fatigue Score as Measured by EORTC QLQ-C30
time Frame
Up to 37.8 months
description
An AE was defined as any untoward medical occurrence in a subject administered a medicinal product that does not necessarily have a causal relationship with this treatment. TEAEs were defined as any AEs that begin or worsen on or after the start of study drug through 30 days after the last dose of the study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0.
measure
Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)
time Frame
Up to 43.4 months
description
Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above
measure
Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (TESAEs)
time Frame
Up to 43.4 months
description
Blood samples were collected for hematology, serum chemistry, and the laboratory abnormalities were assessed. A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the date of last study drug dose plus 30 days.The most severe graded abnormality observed post-baseline for each graded test was counted for each participant. Safety as assessed by grading of laboratory values and AEs according to the National Cancer Institutes' Common Terminology Criteria for Adverse Events (NCI CTCAE) covering grades 0-5 (0=Normal, 1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening, 5=Death). The percentage of participants with worst postbaseline grades 3 or 4 are reported.
measure
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline
time Frame
Up to 43.4 months
description
ECOG performance status (PS) measured on-therapy assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease performance without restriction;1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature;2=Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours;3=Capable of only limited self-care;confined to bed or chair more than 50% of waking hours;4=Completely disabled; cannot carry on any self-care; totally confined to bed or chair;5=Dead. Lower score indicated good performance status. Percentage of participants with Baseline ECOG PS score and corresponding changes to the best values post-baseline have been reported.
measure
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) - Shift From Baseline Value to Best Value During Treatment
time Frame
Up to 43.4 months

Full study description

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).

Source references

references

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