Breast Cancer
Conditions
Brief summary
The primary objective of this study is to compare the efficacy of sacituzumab govitecan to the treatment of physician's choice (TPC) as measured by independently-reviewed Independent Review Committee (IRC) progression-free survival (PFS) in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) previously treated with at least two systemic chemotherapy regimens for unresectable, locally advanced or metastatic disease, and without brain metastasis at baseline.
Interventions
DRUGSacituzumab govitecan
10 mg/kg administered as a slow intravenous (IV) infusion either by gravity or with an infusion pump. Infusion rate for the first 15 minutes will start with 50 mg/hour or less with a subsequent infusion of 100 to 200 mg/hour up to a maximum recommended rate (advanced every 15 to 30 minutes) of 500 mg/hour with a subsequent infusion of 1000 mg/hour.
DRUGEribulin
Administered IV over 2 to 5 minutes at a dose 1.4 mg/m\^2 at North American sites and 1.23 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle for up to 15.3 months. Lower doses will be administered on the same schedule to participants with moderate hepatic impairment (ie, Child-Pugh B; 0.7 mg/m\^2 and 0.67 mg/m\^2 for North American and European sites, respectively).
DRUGCapecitabine
1000 to 1250 mg/m\^2 will be administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period for up to 10.6 months.
DRUGGemcitabine
800 to 1200 mg/m\^2 will be administered IV over 30 minutes on Days 1, 8, and 15 of a 28-day cycle for up to 8.1 months.
DRUGVinorelbine
25 mg/m\^2 will be administered as a weekly IV injection over 6-10 minutes for up to 11.5 months. Vinorelbine will not be allowed as TPC for any participant with Grade 2 neuropathy.
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically or cytologically confirmed TNBC based on the most recent analyzed biopsy or other pathology specimen. Triple negative is defined as \<1% expression for estrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal growth factor receptor 2 (HER2) by in-situ hybridization. * Refractory to or relapsed after at least two prior standard therapeutic regimens for advanced/metastatic TNBC. * Prior exposure to a taxane in localized or advanced/metastatic setting. * Eligible for one of the chemotherapy options listed as TPC (eribulin, capecitabine, gemcitabine, or vinorelbine) as per investigator assessment. * Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1. * Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Bone-only disease is not permitted. * At least 2 weeks beyond prior anti-cancer treatment (chemotherapy, endocrine therapy, radiotherapy, and/or major surgery), and recovered from all acute toxicities to Grade 1 or less (except alopecia and peripheral neuropathy). * At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids \< 20 mg prednisone or equivalent daily are permitted provided the dose is stable for 4 weeks). * Adequate hematology without ongoing transfusional support (hemoglobin \> 9 g/dL, absolute neutrophil count (ANC) \> 1,500 per mm\^3, platelets \> 100,000 per mm\^3). * Adequate renal and hepatic function (creatinine clearance \[CrCL\] \> 60 mL/min, bilirubin ≤ 1.5 institutional upper limit of normal \[IULN\], aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\] ≤ 2.5 x IULN or ≤ 5 x IULN if known liver metastases and serum albumin ≥3 g/dL). * Recovered from all toxicities to Grade 1 or less by National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v4.03 (except alopecia or peripheral neuropathy that may be Grade 2 or less) at the time of randomization. Participants with Grade 2 neuropathy are eligible but may not receive vinorelbine as TPC. * Participants with treated, non-progressive brain metastases, off high-dose steroids (\>20 mg prednisone or equivalent) for at least 4 weeks can be enrolled in the trial. Key
Exclusion criteria
* Women who are pregnant or lactating. * Women of childbearing potential or fertile men unwilling to use effective contraception during study and up to three months after treatment discontinuation in women of child-bearing potential and six months in males post last study drug. * Participants with Gilbert's disease. * Participants with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while participants with other prior malignancies must have had at least a 3-year disease-free interval. * Participants known to be human immunodeficiency (HIV) positive, hepatitis B positive, or hepatitis C positive. * Infection requiring antibiotic use within one week of randomization. * 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. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) by Independent Review Committee (IRC) Assessment in Brain Metastasis Negative (BM-ve) Population | From randomization until objective tumor progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | PFS was defined as the time from randomization until objective tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death, whichever came first. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (greater than or equal to \[≥\] 20%) in the sum of the target lesions or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in BM-ve Population | From the randomization to death from any cause (maximum follow-up duration: 30.8 months) | Overall survival (OS) was defined as the time from the randomization to death from any cause. OS was estimated using Kaplan-Meier estimate. |
| Overall Survival (OS) in ITT Population | From the randomization to death from any cause (maximum follow-up duration: 30.8 months) | Overall survival (OS) was defined as the time from the randomization to death from any cause. OS was estimated using Kaplan-Meier estimate. |
| Objective Response Rate (ORR) by IRC and Investigator Assessment in BM-ve Population | From randomization to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | ORR was defined as the percentage of participants who had the overall best response as either a confirmed complete response (CR) or partial response (PR) relative to the size of population under evaluation. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; and no new lesions. PR: ≥30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; and no new lesions. |
| Time to Objective Response by the Investigator Assessment in BM-ve Population | From randomization to the first recorded objective response (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | Time to response was defined as the time from randomization to the first recorded objective response (ie, CR or PR). CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; and no new lesions. PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and no new lesions. |
| Time to Objective Response by the IRC Assessment in BM-ve Population | From randomization to the first recorded objective response (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | Time to response was defined as the time from randomization to the first recorded objective response (ie, CR or PR). CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; and no new lesions. PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and no new lesions. |
| Duration of Response (DOR) by IRC and Investigator Assessment in BM-ve Population | From the first date of documented response of CR or PR to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | DOR was defined as the number of days between the first date showing a documented response of CR or PR and the date of progression or death. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; and no new lesions. PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and no new lesions. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (≥20%) in the sum of the target lesions or the appearance of new non-target lesions. |
| Progression-Free Survival (PFS) by IRC Assessment in the ITT Population | From randomization until objective tumor progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | PFS was defined as the time from randomization until objective tumor progression by RECIST v1.1 or death, whichever came first. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (≥20%) in the sum of the target lesions or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate. |
| Time to Progression (TTP) by IRC Assessment in BM-ve Population | From randomization until disease progression (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | Time to Progression (TTP) was defined as the time from the date of randomization to the date of the first evidence of disease progression as assessed using RECIST 1.1 criteria. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (≥20%) in the sum of the target lesions or the appearance of new non-target lesions. Participants without progression were censored. |
| Clinical Benefit Rate (CBR) by IRC and Investigator Assessment in BM-ve Population | From randomization to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | CBR was defined as the percentage of participants with best response as either CR, PR, or stable disease (SD) with a duration of ≥6 months. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; and no new lesions. PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and no new lesions. 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; and Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. PD: ≥20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since treatment started or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
| Percentage of Participants Experiencing Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation of Study Drug | First dose date up to last follow-up (maximum up to 30.8 months) | 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 4.03. 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 |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Baseline; End of Treatment (EOT) (up to 29.6 months) | The EORTC QLQ-C30 is a questionnaire to assess quality of life (QoL), it is composed of 30 questions (items) resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning), 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. Higher score for the functioning scales and global health status indicate a better quality of life; a positive change from baseline indicates improvement. Lower scores on the symptom and single-item scales indicate a better quality of life; a negative change from baseline indicates improvement. |
| Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | First dose date up to last follow-up (maximum up to 30.8 months) | Blood samples were collected for hematology, serum chemistry and the laboratory abnormalities were assessed. 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 to Progression (TTP) by Investigator Assessment in BM-ve Population | From randomization until disease progression (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | Time to Progression (TTP) was defined as the time from the date of randomization to the date of the first evidence of disease progression as assessed using RECIST 1.1 criteria. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (≥20%) in the sum of the target lesions or the appearance of new non-target lesions. Participants without progression were censored. |
Countries
Belgium, Canada, France, Germany, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Belgium, Canada, France, Germany, Spain, the United Kingdom, and the United States. The first participant was screened on 07 November 2017. The last study visit occurred on 08 December 2020.
Pre-assignment details
730 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Sacituzumab Govitecan Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion either by gravity or with an infusion pump on Days 1 and 8 of a 21-day treatment cycle for up to 29.6 months. Infusion rate for the first 15 minutes started with 50 mg/hour or less with a subsequent infusion of 100 to 200 mg/hour up to a maximum recommended rate (advanced every 15 to 30 minutes) of 500 mg/hour with a subsequent infusion of 1000 mg/hour. Participants continued treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable AEs. | 267 |
| Treatment of Physician's Choice (TPC) Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent regimen that was selected by the investigator before participant randomization. Participants continued treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable AEs.
Eribulin was administered IV over 2 to 5 minutes at a dose 1.4 mg/m\^2 at North American sites and 1.23 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle for up to 15.3 months. Lower doses were administered on the same schedule to participants with moderate hepatic impairment (ie, Child-Pugh B; 0.7 mg/m\^2 and 0.67 mg/m\^2 for North American and European sites, respectively).
Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period for up to 10.6 months.
Gemcitabine 800 to 1200 mg/m\^2 was administered IV over 30 minutes on Days 1, 8, and 15 of a 28-day cycle for up to 8.1 months.
Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection over 6-10 minutes for up to 11.5 months. Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy. | 262 |
| Total | 529 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 197 | 210 |
| Overall Study | Lost to Follow-up | 4 | 4 |
| Overall Study | Sponsor's Decision | 55 | 20 |
| Overall Study | Withdrawal of Consent | 11 | 28 |
Baseline characteristics
| Characteristic | Sacituzumab Govitecan | Treatment of Physician's Choice (TPC) | Total |
|---|---|---|---|
| Age, Continuous | 54.0 years STANDARD_DEVIATION 11.34 | 54.0 years STANDARD_DEVIATION 11.69 | 54.0 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 25 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 234 Participants | 226 Participants | 460 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants | 11 Participants | 24 Participants |
| Race/Ethnicity, Customized Race Asian | 13 Participants | 9 Participants | 22 Participants |
| Race/Ethnicity, Customized Race Black | 28 Participants | 34 Participants | 62 Participants |
| Race/Ethnicity, Customized Race Other | 11 Participants | 16 Participants | 27 Participants |
| Race/Ethnicity, Customized Race White | 215 Participants | 203 Participants | 418 Participants |
| Region of Enrollment Belgium | 20 participants | 25 participants | 45 participants |
| Region of Enrollment Canada | 3 participants | 2 participants | 5 participants |
| Region of Enrollment France | 33 participants | 29 participants | 62 participants |
| Region of Enrollment Germany | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Spain | 32 participants | 26 participants | 58 participants |
| Region of Enrollment United Kingdom | 7 participants | 8 participants | 15 participants |
| Region of Enrollment United States | 172 participants | 170 participants | 342 participants |
| Sex: Female, Male Female | 265 Participants | 262 Participants | 527 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 201 / 267 | 222 / 262 |
| other Total, other adverse events | 256 / 258 | 213 / 224 |
| serious Total, serious adverse events | 69 / 258 | 64 / 224 |
Outcome results
Primary
Progression-Free Survival (PFS) by Independent Review Committee (IRC) Assessment in Brain Metastasis Negative (BM-ve) Population
PFS was defined as the time from randomization until objective tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death, whichever came first. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (greater than or equal to \[≥\] 20%) in the sum of the target lesions or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate.
Time frame: From randomization until objective tumor progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months)
Population: The BM-ve Population included all randomized participants who were randomized to the strata of no baseline brain metastasis at the time of randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sacituzumab Govitecan | Progression-Free Survival (PFS) by Independent Review Committee (IRC) Assessment in Brain Metastasis Negative (BM-ve) Population | 5.6 months |
| Treatment of Physician's Choice (TPC) | Progression-Free Survival (PFS) by Independent Review Committee (IRC) Assessment in Brain Metastasis Negative (BM-ve) Population | 1.7 months |
p-value: <0.000195% CI: [0.305, 0.492]Log Rank
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score
The EORTC QLQ-C30 is a questionnaire to assess quality of life (QoL), it is composed of 30 questions (items) resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning), 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. Higher score for the functioning scales and global health status indicate a better quality of life; a positive change from baseline indicates improvement. Lower scores on the symptom and single-item scales indicate a better quality of life; a negative change from baseline indicates improvement.
Time frame: Baseline; End of Treatment (EOT) (up to 29.6 months)
Population: Participants in the Safety analysis set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Nausea and Vomiting: Change From Baseline at EOT | 5.2 score on a scale | Standard Deviation 23.93 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Cognitive Functioning: Baseline | 81.7 score on a scale | Standard Deviation 21.08 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Pain: Baseline | 37.9 score on a scale | Standard Deviation 30.54 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Global Health Status/QoL: Change From Baseline at EOT | -5.8 score on a scale | Standard Deviation 22.71 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Pain: Change From Baseline at EOT | 2.8 score on a scale | Standard Deviation 27.84 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Cognitive Functioning: Change From Baseline at EOT | -7.5 score on a scale | Standard Deviation 22.81 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Dyspnoea: Baseline | 25.4 score on a scale | Standard Deviation 30.36 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Role Functioning: Change From Baseline at EOT | -8.4 score on a scale | Standard Deviation 32.87 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Dyspnoea: Change From Baseline at EOT | 0.7 score on a scale | Standard Deviation 30.91 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Social Functioning: Baseline | 69.1 score on a scale | Standard Deviation 29.96 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Insomnia: Baseline | 33.2 score on a scale | Standard Deviation 30.95 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Physical Functioning: Change From Baseline at EOT | -4.6 score on a scale | Standard Deviation 21.07 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Insomnia: Change From Baseline at EOT | 4.4 score on a scale | Standard Deviation 34.67 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Social Functioning: Change From Baseline at EOT | -5.9 score on a scale | Standard Deviation 27.52 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Appetite Loss: Baseline | 20.8 score on a scale | Standard Deviation 27.34 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Emotional Functioning: Baseline | 71.9 score on a scale | Standard Deviation 22.33 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Appetite Loss: Change From Baseline at EOT | 3.1 score on a scale | Standard Deviation 31.78 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Fatigue: Baseline | 39.4 score on a scale | Standard Deviation 25.72 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Constipation: Baseline | 17.7 score on a scale | Standard Deviation 27.18 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Physical Functioning: Baseline | 73.2 score on a scale | Standard Deviation 21.69 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Constipation: Change From Baseline at EOT | 3.3 score on a scale | Standard Deviation 28.92 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Fatigue: Change From Baseline at EOT | 5.1 score on a scale | Standard Deviation 25.93 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Diarrhoea: Baseline | 7.2 score on a scale | Standard Deviation 17.73 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Emotional Functioning: Change From Baseline at EOT | -3.8 score on a scale | Standard Deviation 25.02 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Diarrhoea: Change From Baseline at EOT | 11.4 score on a scale | Standard Deviation 28.56 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Nausea and Vomiting: Baseline | 8.3 score on a scale | Standard Deviation 16.36 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Financial Difficulties: Baseline | 27.6 score on a scale | Standard Deviation 34.39 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Role Functioning: Baseline | 68.1 score on a scale | Standard Deviation 30.35 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Financial Difficulties: Change From Baseline at EOT | 0.4 score on a scale | Standard Deviation 24.09 |
| Sacituzumab Govitecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Global Health Status/QoL: Baseline | 61.9 score on a scale | Standard Deviation 21.31 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Financial Difficulties: Change From Baseline at EOT | 1.1 score on a scale | Standard Deviation 23.54 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Global Health Status/QoL: Baseline | 56.4 score on a scale | Standard Deviation 22.21 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Global Health Status/QoL: Change From Baseline at EOT | -9.4 score on a scale | Standard Deviation 20.46 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Physical Functioning: Baseline | 71.2 score on a scale | Standard Deviation 21.24 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Physical Functioning: Change From Baseline at EOT | -13.5 score on a scale | Standard Deviation 20.54 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Role Functioning: Baseline | 65.1 score on a scale | Standard Deviation 30.31 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Role Functioning: Change From Baseline at EOT | -18.8 score on a scale | Standard Deviation 29.83 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Emotional Functioning: Baseline | 68.9 score on a scale | Standard Deviation 23.87 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Emotional Functioning: Change From Baseline at EOT | -3.5 score on a scale | Standard Deviation 22.16 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Cognitive Functioning: Baseline | 79.5 score on a scale | Standard Deviation 23.91 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Cognitive Functioning: Change From Baseline at EOT | -6.1 score on a scale | Standard Deviation 22.92 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Social Functioning: Baseline | 69.6 score on a scale | Standard Deviation 26.88 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Social Functioning: Change From Baseline at EOT | -10.3 score on a scale | Standard Deviation 29.6 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Fatigue: Baseline | 42.1 score on a scale | Standard Deviation 25.99 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Fatigue: Change From Baseline at EOT | 14.0 score on a scale | Standard Deviation 23.05 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Nausea and Vomiting: Baseline | 10.3 score on a scale | Standard Deviation 18.26 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Nausea and Vomiting: Change From Baseline at EOT | 7.3 score on a scale | Standard Deviation 23.33 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Pain: Baseline | 42.5 score on a scale | Standard Deviation 30.38 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Pain: Change From Baseline at EOT | 6.8 score on a scale | Standard Deviation 30.33 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Dyspnoea: Baseline | 25.0 score on a scale | Standard Deviation 29.09 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Dyspnoea: Change From Baseline at EOT | 5.9 score on a scale | Standard Deviation 28.95 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Insomnia: Baseline | 35.6 score on a scale | Standard Deviation 31.42 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Insomnia: Change From Baseline at EOT | -4.3 score on a scale | Standard Deviation 32.24 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Appetite Loss: Baseline | 25.8 score on a scale | Standard Deviation 28.68 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Appetite Loss: Change From Baseline at EOT | 10.0 score on a scale | Standard Deviation 30.32 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Constipation: Baseline | 19.0 score on a scale | Standard Deviation 26.56 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Constipation: Change From Baseline at EOT | 7.0 score on a scale | Standard Deviation 31.27 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Diarrhoea: Baseline | 6.5 score on a scale | Standard Deviation 15.69 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Diarrhoea: Change From Baseline at EOT | 3.6 score on a scale | Standard Deviation 22.46 |
| Treatment of Physician's Choice (TPC) | Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score | Financial Difficulties: Baseline | 22.4 score on a scale | Standard Deviation 30.91 |
Secondary
Clinical Benefit Rate (CBR) by IRC and Investigator Assessment in BM-ve Population
CBR was defined as the percentage of participants with best response as either CR, PR, or stable disease (SD) with a duration of ≥6 months. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; and no new lesions. PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and no new lesions. 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; and Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. PD: ≥20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since treatment started or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: From randomization to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months)
Population: Participants in the BM-ve Population were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sacituzumab Govitecan | Clinical Benefit Rate (CBR) by IRC and Investigator Assessment in BM-ve Population | IRC Assessment | 44.7 percentage of participants |
| Sacituzumab Govitecan | Clinical Benefit Rate (CBR) by IRC and Investigator Assessment in BM-ve Population | Investigator Assessment | 45.5 percentage of participants |
| Treatment of Physician's Choice (TPC) | Clinical Benefit Rate (CBR) by IRC and Investigator Assessment in BM-ve Population | IRC Assessment | 8.6 percentage of participants |
| Treatment of Physician's Choice (TPC) | Clinical Benefit Rate (CBR) by IRC and Investigator Assessment in BM-ve Population | Investigator Assessment | 10.3 percentage of participants |
Comparison: CBR by IRC Assessmentp-value: <0.000195% CI: [5.055, 14.437]Cochran-Mantel-Haenszel
Comparison: CBR by Investigator Assessmentp-value: <0.000195% CI: [4.54, 12.364]Cochran-Mantel-Haenszel
Secondary
Duration of Response (DOR) by IRC and Investigator Assessment in BM-ve Population
DOR was defined as the number of days between the first date showing a documented response of CR or PR and the date of progression or death. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; and no new lesions. PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and no new lesions. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (≥20%) in the sum of the target lesions or the appearance of new non-target lesions.
Time frame: From the first date of documented response of CR or PR to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months)
Population: Participants in the BM-ve Population with objective response were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sacituzumab Govitecan | Duration of Response (DOR) by IRC and Investigator Assessment in BM-ve Population | IRC Assessment | 6.3 months |
| Sacituzumab Govitecan | Duration of Response (DOR) by IRC and Investigator Assessment in BM-ve Population | Investigator Assessment | 6.9 months |
| Treatment of Physician's Choice (TPC) | Duration of Response (DOR) by IRC and Investigator Assessment in BM-ve Population | IRC Assessment | 3.6 months |
| Treatment of Physician's Choice (TPC) | Duration of Response (DOR) by IRC and Investigator Assessment in BM-ve Population | Investigator Assessment | 3.0 months |
Comparison: DOR by IRC Assessmentp-value: 0.068395% CI: [0.15, 1.107]Log Rank
Comparison: DOR by Investigator Assessmentp-value: <0.000195% CI: [0.103, 0.435]Log Rank
Secondary
Objective Response Rate (ORR) by IRC and Investigator Assessment in BM-ve Population
ORR was defined as the percentage of participants who had the overall best response as either a confirmed complete response (CR) or partial response (PR) relative to the size of population under evaluation. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; and no new lesions. PR: ≥30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; and no new lesions.
Time frame: From randomization to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months)
Population: Participants in the BM-ve Population with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sacituzumab Govitecan | Objective Response Rate (ORR) by IRC and Investigator Assessment in BM-ve Population | ORR by IRC Assessment | 34.9 percentage of participants |
| Sacituzumab Govitecan | Objective Response Rate (ORR) by IRC and Investigator Assessment in BM-ve Population | ORR by Investigator Assessment | 33.2 percentage of participants |
| Treatment of Physician's Choice (TPC) | Objective Response Rate (ORR) by IRC and Investigator Assessment in BM-ve Population | ORR by IRC Assessment | 4.7 percentage of participants |
| Treatment of Physician's Choice (TPC) | Objective Response Rate (ORR) by IRC and Investigator Assessment in BM-ve Population | ORR by Investigator Assessment | 6.4 percentage of participants |
Comparison: ORR by IRC Assessmentp-value: <0.000195% CI: [5.59, 21.095]Cochran-Mantel-Haenszel
Comparison: ORR by Investigator Assessmentp-value: <0.000195% CI: [4.063, 13.341]Cochran-Mantel-Haenszel
Secondary
Overall Survival (OS) in BM-ve Population
Overall survival (OS) was defined as the time from the randomization to death from any cause. OS was estimated using Kaplan-Meier estimate.
Time frame: From the randomization to death from any cause (maximum follow-up duration: 30.8 months)
Population: Participants in the BM-ve Population were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sacituzumab Govitecan | Overall Survival (OS) in BM-ve Population | 12.1 months |
| Treatment of Physician's Choice (TPC) | Overall Survival (OS) in BM-ve Population | 6.7 months |
p-value: <0.000195% CI: [0.39, 0.592]Log Rank
Secondary
Overall Survival (OS) in ITT Population
Overall survival (OS) was defined as the time from the randomization to death from any cause. OS was estimated using Kaplan-Meier estimate.
Time frame: From the randomization to death from any cause (maximum follow-up duration: 30.8 months)
Population: Participants in the ITT Population were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sacituzumab Govitecan | Overall Survival (OS) in ITT Population | 11.8 months |
| Treatment of Physician's Choice (TPC) | Overall Survival (OS) in ITT Population | 6.9 months |
p-value: <0.000195% CI: [0.422, 0.625]Log Rank
Secondary
Percentage of Participants Experiencing Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation of Study Drug
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 4.03. 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: First dose date up to last follow-up (maximum up to 30.8 months)
Population: Safety Population included all participants who received at least one dose of sacituzumab govitecan or TPC.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sacituzumab Govitecan | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation of Study Drug | Any TEAEs | 99.6 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation of Study Drug | SAEs | 26.7 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation of Study Drug | TEAEs Leading to Discontinuation of Study Drug | 4.7 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation of Study Drug | Any TEAEs | 97.8 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation of Study Drug | SAEs | 28.6 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation of Study Drug | TEAEs Leading to Discontinuation of Study Drug | 5.4 percentage of participants |
Secondary
Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline
Blood samples were collected for hematology, serum chemistry and the laboratory abnormalities were assessed. 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: First dose date up to last follow-up (maximum up to 30.8 months)
Population: Participants in the Safety analysis set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hyperglycemia | 3.1 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Neutrophil Count Decreased | 48.8 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hyperkalemia | 0.8 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Alkaline Phosphatase Increased | 3.1 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypermagnesemia | 0.4 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Lymphocyte Count Decreased | 33.3 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypernatremia | 0 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Aspartate Aminotransferase Increased | 3.5 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypoalbumenemia | 0.8 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Platelet Count Decreased | 1.2 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypocalcemia | 1.6 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Blood Bilirubin Increased | 1.9 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypoglycemia | 0.4 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Anemia | 8.9 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypokalemia | 4.3 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Creatinine Increased | 0.4 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypomagnesemia | 0.8 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | White Blood Cell Decreased | 41.1 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hyponatremia | 3.9 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypercalcemia | 0 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypophosphatemia | 8.1 percentage of participants |
| Sacituzumab Govitecan | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Alanine Aminotransferase Increased | 1.2 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypophosphatemia | 3.6 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Anemia | 5.4 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Lymphocyte Count Decreased | 25.0 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Neutrophil Count Decreased | 35.3 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Platelet Count Decreased | 2.7 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Alanine Aminotransferase Increased | 2.2 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Alkaline Phosphatase Increased | 3.6 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Aspartate Aminotransferase Increased | 2.2 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Blood Bilirubin Increased | 2.7 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Creatinine Increased | 0 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypercalcemia | 0.4 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hyperglycemia | 3.1 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hyperkalemia | 0 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypermagnesemia | 0.4 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypernatremia | 0 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypoalbumenemia | 1.3 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypocalcemia | 1.3 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypoglycemia | 0 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypokalemia | 0.9 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hypomagnesemia | 0 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | Hyponatremia | 3.6 percentage of participants |
| Treatment of Physician's Choice (TPC) | Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline | White Blood Cell Decreased | 25.4 percentage of participants |
Secondary
Progression-Free Survival (PFS) by IRC Assessment in the ITT Population
PFS was defined as the time from randomization until objective tumor progression by RECIST v1.1 or death, whichever came first. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (≥20%) in the sum of the target lesions or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate.
Time frame: From randomization until objective tumor progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months)
Population: The ITT Population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sacituzumab Govitecan | Progression-Free Survival (PFS) by IRC Assessment in the ITT Population | 4.8 months |
| Treatment of Physician's Choice (TPC) | Progression-Free Survival (PFS) by IRC Assessment in the ITT Population | 1.7 months |
p-value: <0.000195% CI: [0.33, 0.517]Log Rank
Secondary
Time to Objective Response by the Investigator Assessment in BM-ve Population
Time to response was defined as the time from randomization to the first recorded objective response (ie, CR or PR). CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; and no new lesions. PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and no new lesions.
Time frame: From randomization to the first recorded objective response (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months)
Population: Participants in the BM-ve Population with objective response were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sacituzumab Govitecan | Time to Objective Response by the Investigator Assessment in BM-ve Population | 2.14 months | Standard Deviation 1.322 |
| Treatment of Physician's Choice (TPC) | Time to Objective Response by the Investigator Assessment in BM-ve Population | 2.72 months | Standard Deviation 2.933 |
Secondary
Time to Objective Response by the IRC Assessment in BM-ve Population
Time to response was defined as the time from randomization to the first recorded objective response (ie, CR or PR). CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; and no new lesions. PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and no new lesions.
Time frame: From randomization to the first recorded objective response (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months)
Population: Participants in the BM-ve Population with objective response were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sacituzumab Govitecan | Time to Objective Response by the IRC Assessment in BM-ve Population | 2.67 months | Standard Deviation 1.913 |
| Treatment of Physician's Choice (TPC) | Time to Objective Response by the IRC Assessment in BM-ve Population | 1.86 months | Standard Deviation 0.919 |
Secondary
Time to Progression (TTP) by Investigator Assessment in BM-ve Population
Time to Progression (TTP) was defined as the time from the date of randomization to the date of the first evidence of disease progression as assessed using RECIST 1.1 criteria. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (≥20%) in the sum of the target lesions or the appearance of new non-target lesions. Participants without progression were censored.
Time frame: From randomization until disease progression (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months)
Population: Participants in the BM-ve Population were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sacituzumab Govitecan | Time to Progression (TTP) by Investigator Assessment in BM-ve Population | 5.7 months |
| Treatment of Physician's Choice (TPC) | Time to Progression (TTP) by Investigator Assessment in BM-ve Population | 1.8 months |
Comparison: TTP by Investigator Assessmentp-value: <0.000195% CI: [0.248, 0.404]Log Rank
Secondary
Time to Progression (TTP) by IRC Assessment in BM-ve Population
Time to Progression (TTP) was defined as the time from the date of randomization to the date of the first evidence of disease progression as assessed using RECIST 1.1 criteria. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (≥20%) in the sum of the target lesions or the appearance of new non-target lesions. Participants without progression were censored.
Time frame: From randomization until disease progression (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months)
Population: Participants in the BM-ve Population were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sacituzumab Govitecan | Time to Progression (TTP) by IRC Assessment in BM-ve Population | 5.8 months |
| Treatment of Physician's Choice (TPC) | Time to Progression (TTP) by IRC Assessment in BM-ve Population | 2.1 months |
Comparison: TTP by IRC Assessmentp-value: <0.000195% CI: [0.315, 0.525]Log Rank