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

Gilead Sciences543 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

543

Conditions

Metastatic Breast Cancer

Interventions

Sacituzumab Govitecan-hziyDRUG

Administered intravenously

EribulinDRUG

Administered intravenously per NCCN guidelines

CapecitabineDRUG

Administered orally per NCCN guidelines

Gemcitabine

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (113)

Outcomes

Primary Outcomes

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

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.

Time frame: Up to 42.8 months

Secondary Outcomes

Overall Survival (OS)

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.

Time frame: Up to 42.8 months

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

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.

Time frame: Up to 42.8 months

Duration of Response (DOR) by BICR and LIR Assessment

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.

Data from ClinicalTrials.gov

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Administered intravenously per NCCN guidelines

VinorelbineDRUG

Administered intravenously per NCCN guidelines

HonorHealth Research Institute

Avondale, Arizona, United States

Arizona Oncology Associates, PC

Tucson, Arizona, United States

Highlands Oncology Group

Fayetteville, Arkansas, United States

University of California, San Diego Moores Cancer Center

La Jolla, California, United States

Los Angeles Hematology Oncology Medical Group

Los Angeles, California, United States

UCLA Department of Medicine - Hematology/Oncology

Los Angeles, California, United States

University of California, Irvine Medical Center-Chao Family Comprehensive Cancer Center

Orange, California, United States

Southern California Permanente Medical Group

San Diego, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Rocky Mountain Cancer Centers

Aurora, Colorado, United States

...and 103 more locations

Time frame: Up to 42.8 months

Clinical Benefit Rate (CBR) by BICR and LIR Assessment

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.

Time frame: Up to 42.8 months

PFS by LIR Assessment

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.

Time frame: Up to 42.8 months

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)

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.

Time frame: Up to 37.8 months

TTD of Pain Score as Measured by EORTC QLQ-C30

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).

Time frame: Up to 37.8 months

TTD of Fatigue Score as Measured by EORTC QLQ-C30

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).

Time frame: Up to 37.8 months

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

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.

Time frame: Up to 43.4 months

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

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

Time frame: Up to 43.4 months

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

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.

Time frame: Up to 43.4 months

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

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.

Time frame: Up to 43.4 months