Gastric Adenocarcinoma, Esophageal Cancer, Hepatocellular Carcinoma, Non-small Cell Lung Cancer, Small Cell Lung Cancer, Ovarian Epithelial Cancer, Carcinoma Breast Stage IV, Hormone-refractory Prostate Cancer, Head and Neck Cancers- Squamous Cell, Renal Cell Cancer, Urinary Bladder Neoplasms, Cervical Cancer, Endometrial Cancer, Glioblastoma Multiforme, Triple Negative Breast Cancer, Pancreatic Cancer
Conditions
Brief summary
The primary objective in Phase I is to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent administered in 21-day treatment cycles in previously treated participants with advanced epithelial cancer. In Phase II, the primary objective is to evaluate the safety and efficacy of sacituzumab govitecan-hziy administered in 21-day treatment cycles at a dose selected in Phase I. Tumor types in the study will include: cervical, colorectal, endometrial, ovarian, esophageal, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular, prostate, non-small-cell lung cancer, pancreatic, renal cell, small-cell lung cancer, non-triple negative breast cancer (non-TNBC), triple-negative breast cancer (TNBC) and metastatic urothelial cancer (mUC).
Detailed description
The outcome measures are planned to be assessed up to the data cutoff date. Following the data cutoff date, the participants will either stay on the study and will be followed for safety data collection or rolled into another Gilead-sponsored study. Therefore, only safety data will be collected after the data cutoff date.
Interventions
Administered via intravenous (IV) infusion
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Individuals able to understand and give written informed consent. * Histologically or cytologically confirmed epithelial cancer of one of the following types: * Gastric adenocarcinoma (GC) * Esophageal cancer (EC) * Hepatocellular carcinoma (HCC) * Non-small-cell lung cancer (NSCLC) * Small-cell lung cancer (SCLC) * Epithelial ovarian cancer (EOC) * Cervical Cancer * Endometrial Cancer * Triple-negative breast cancer (TNBC) * Non-triple-negative breast cancer * Papillary thyroid cancer (excludes follicular, medullary, Hurthle cell, and anaplastic thyroid cancer) * Glioblastoma multiforme (GBM) * Hormone-refractory prostate cancer (HRPC) * Head and neck cancers- squamous cell (SCCHN) * Renal cell cancer (clear cell) (RCC) * Urothelial cancer * Stage IV (metastatic) disease (except for individuals with GBM). * Refractory to or relapsed after at least one prior standard therapeutic regimen * Adequate performance status (ECOG 0 or 1) * Expected survival ≥ 6 months. * Measurable disease by CT or MRI. * At least 2 weeks beyond treatment (chemotherapy, investigational drugs including small molecular inhibitors, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities to Grade 1 or less (except alopecia). * At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids \< 20 mg prednisone or equivalent daily are permitted). * 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 ≤ 2.0 x institutional upper limit of normal (IULN), bilirubin ≤ 1.5 IULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x IULN or 5 x IULN if know liver metastases). * Otherwise, all toxicity at study entry ≤ Grade 1.
Exclusion criteria
* Women who are pregnant or lactating. * Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period. * Individuals with Gilbert's disease. * Individuals with brain metastases can be enrolled only if treated, non-progressive brain metastases and off high-dose steroids (\> 20 mg prednisone or equivalent) for at least 4 weeks. * Presence of bulky disease (defined as any single mass \> 7 cm in its greatest dimension). Individuals with a mass over 7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the medical monitor. * Individuals with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction. * Individuals with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while individuals with other prior malignancies must have had at least a 3-year disease-free interval. * Individuals known to be HIV positive, hepatitis B positive, or hepatitis C positive. * Known history of unstable angina, MI, or CHF present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy. * Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months. * Prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of initiation of study treatment. * Infection requiring intravenous antibiotic use within 1 week. * History of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI toxicity to prior irinotecan, * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events | First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months) plus 30 days | 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 Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population. |
| Percentage of Participants Who Permanently Discontinued Sacituzumab Govitecan-hziy (SG) Due to Any Adverse Events, Excluding Adverse Events Leading to Death | First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months) | Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP). |
| Percentage of Participants Who Required Dose Interruption Due to Any Adverse Events | First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months) | Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP). |
| Objective Response Rate (ORR) by Independent Central Review (ICR) | Up to data cutoff date of 01 March 2019 (maximum duration: 74 months) | ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by ICR assessment according to RECIST1.1. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to \<10 mm. PR was defined as ≥ 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only. |
| Objective Response Rate by Local Assessment | Up to data cutoff date of 01 March 2019 (maximum duration: 74 months) | ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by local assessment. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to \<10 mm. PR was defined as ≥3 0% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by Local Assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) by Local Assessment | Up to data cutoff date of 01 March 2019 (maximum duration: 74 months) | Progression-free survival (PFS) was defined as the interval from the first dose start date to the date of disease progression defined as documented progressive disease (PD) or death from any cause, whichever occurs first. Per planned analysis, PFS by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population. |
| Overall Survival by Local Assessment | Up to data cutoff date of 01 March 2019 (maximum duration: 74 months) | Overall survival was defined as the time from the date of the first dose start date to the date of death due to any cause. Per planned analysis, overall survival by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population. |
| Pharmacokinetic (PK) Parameter: T1/2 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hours (± 30 minutes) for subsequent infusions | T1/2 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. T1/2 is defined as apparent terminal elimination half-life (h); calculated as 0.693/λz. The dose level evaluated for PK analysis was 10 mg/kg. |
| Duration of Response by ICR | Up to data cutoff date of 01 March 2019 (maximum duration: 74 months) | Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only. |
| PK Parameter: AUC0-168 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions | AUC0-168 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-168 is defined as area under the serum concentration-time curve from time 0 to 168 hours. The dose level evaluated for PK analysis was 10 mg/kg. |
| PK Parameter: AUC0-inf of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions | AUC0-inf was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-inf is defined as area under the serum concentration-time curve from time 0 extrapolated to infinity. The dose level evaluated for PK analysis was 10 mg/kg. |
| PK Parameter: Cmax of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions | Cmax was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. Cmax is defined as maximum observed serum concentration obtained directly from the observed concentration-time data. The dose level evaluated for PK analysis was 10 mg/kg. |
| PK Parameter: AUC0-24 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions | AUC0-24 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-24 is defined as area under the serum concentration-time curve from time 0 to 24 hours. The dose level evaluated for PK analysis was 10 mg/kg. |
| Duration of Response by Local Assessment | Up to data cutoff date of 01 March 2019 (maximum duration: 74 months) | Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Per planned analysis, duration of response by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population. |
| Time to Response by ICR | Up to data cutoff date of 01 March 2019 (maximum duration: 74 months) | Time to response was defined as the time from the first dose to the first documentation of response (PR or CR). Per planned analysis, time to response by ICR was assessed for the TNBC Target Population only. |
| Time to Response by Local Assessments | Up to data cutoff date of 01 March 2019 (maximum duration: 74 months) | Time to response was defined as the time from the first dose to the first documentation of response (PR or CR). Per planned analysis, time to response by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population. |
| Clinical Benefit Rate (CBR) by Local Assessment | Up to data cutoff date of 01 March 2019 (maximum duration: 74 months) | Clinical benefit rate (CR+PR+\[stable disease (SD) ≥ 6 months\]) is defined as those participants with best response as CR or PR or else SD with a duration of at least 6 months. SD for 6 months duration was defined as the time from the first dose to the first documentation of PD or to the last adequate response assessment prior to data cut-off date, whichever is earlier. Per planned analysis, CBR by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States. The first participant was screened on 17 December 2012. The last study visit occurred on 13 August 2020. Outcome Measures were assessed up to the data cutoff date of 01 March 2019. Following the data cutoff date, the participants either stayed on the study and were followed for safety data collection or rolled into another Gilead-sponsored study. Therefore, only safety data was collected after the data cutoff date.
Pre-assignment details
Tumor types included in the study were as follows: cervical, colorectal, endometrial, ovarian, esophageal, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular, prostate, non-small-cell lung cancer, pancreatic, renal cell, small-cell lung cancer, non-triple negative breast cancer (non-TNBC), triple-negative breast cancer (TNBC) and metastatic urothelial cancer (mUC).
Participants by arm
| Arm | Count |
|---|---|
| SG 8mg/kg Participants received sacituzumab govitecan-hziy 8 mg/kg of body weight via IV infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity. | 81 |
| SG 10 mg/kg Participants received sacituzumab govitecan-hziy 10 mg/kg of body weight via IV infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity. | 402 |
| SG 12 mg/kg Participants received sacituzumab govitecan-hziy 12 mg/kg of body weight via IV infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity. | 9 |
| SG 18 mg/kg Participants received sacituzumab govitecan-hziy 18 mg/kg of body weight via IV infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity. | 3 |
| Total | 495 |
Baseline characteristics
| Characteristic | SG 10 mg/kg | SG 12 mg/kg | SG 8mg/kg | SG 18 mg/kg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 11.28 | 59.1 years STANDARD_DEVIATION 10.53 | 61.1 years STANDARD_DEVIATION 10.91 | 56.0 years STANDARD_DEVIATION 4 | 60.0 years STANDARD_DEVIATION 11.17 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 16 Participants | 0 Participants | 4 Participants | 0 Participants | 20 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 386 Participants | 9 Participants | 77 Participants | 3 Participants | 475 Participants |
| Race/Ethnicity, Customized Race Asian | 13 Participants | 1 Participants | 4 Participants | 0 Participants | 18 Participants |
| Race/Ethnicity, Customized Race Black | 19 Participants | 2 Participants | 6 Participants | 0 Participants | 27 Participants |
| Race/Ethnicity, Customized Race Other | 41 Participants | 0 Participants | 4 Participants | 0 Participants | 45 Participants |
| Race/Ethnicity, Customized Race White | 329 Participants | 6 Participants | 67 Participants | 3 Participants | 405 Participants |
| Sex: Female, Male Female | 281 Participants | 6 Participants | 46 Participants | 1 Participants | 334 Participants |
| Sex: Female, Male Male | 121 Participants | 3 Participants | 35 Participants | 2 Participants | 161 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 422 / 495 |
| other Total, other adverse events | 490 / 495 |
| serious Total, serious adverse events | 192 / 495 |
Outcome results
Primary
Objective Response Rate by Local Assessment
ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by local assessment. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to \<10 mm. PR was defined as ≥3 0% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by Local Assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time frame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
Population: * Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease \& who received at least 1 dose of 10 mg/kg SG~* HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy \& who received at least 1 dose of 10 mg/kg SG~* mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments \& who received at least 1 dose of 10 mg/kg SG
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TNBC Target Population | Objective Response Rate by Local Assessment | 33.3 Percentage of participants |
| HR+/HER2- mBC Population | Objective Response Rate by Local Assessment | 31.5 Percentage of participants |
| mUC Population | Objective Response Rate by Local Assessment | 28.9 Percentage of participants |
Primary
Objective Response Rate (ORR) by Independent Central Review (ICR)
ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by ICR assessment according to RECIST1.1. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to \<10 mm. PR was defined as ≥ 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only.
Time frame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
Population: Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease and who received SG at a dose of 10 mg/kg.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TNBC Target Population | Objective Response Rate (ORR) by Independent Central Review (ICR) | 34.3 Percentage of participants |
Primary
Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events
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 Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population.
Time frame: First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months) plus 30 days
Population: * Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease \& who received at least 1 dose of 10 mg/kg SG~* HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy \& who received at least 1 dose of 10 mg/kg SG~* mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments \& who received at least 1 dose of 10 mg/kg SG~* OSP: All participants who received at least 1 dose of SG
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TNBC Target Population | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events | Adverse Events | 100.0 Percentage of participants |
| TNBC Target Population | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events | Serious Adverse Events | 30.6 Percentage of participants |
| HR+/HER2- mBC Population | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events | Serious Adverse Events | 35.2 Percentage of participants |
| HR+/HER2- mBC Population | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events | Adverse Events | 100.0 Percentage of participants |
| mUC Population | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events | Adverse Events | 100.0 Percentage of participants |
| mUC Population | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events | Serious Adverse Events | 42.2 Percentage of participants |
| Overall Safety Population (OSP) | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events | Adverse Events | 99.8 Percentage of participants |
| Overall Safety Population (OSP) | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events | Serious Adverse Events | 38.8 Percentage of participants |
Primary
Percentage of Participants Who Permanently Discontinued Sacituzumab Govitecan-hziy (SG) Due to Any Adverse Events, Excluding Adverse Events Leading to Death
Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP).
Time frame: First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)
Population: * Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease \& who received at least 1 dose of 10 mg/kg SG~* HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy \& who received at least 1 dose of 10 mg/kg SG~* mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments \& who received at least 1 dose of 10 mg/kg SG~* OSP: All participants who received at least 1 dose of SG
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TNBC Target Population | Percentage of Participants Who Permanently Discontinued Sacituzumab Govitecan-hziy (SG) Due to Any Adverse Events, Excluding Adverse Events Leading to Death | 2.8 Percentage of participants |
| HR+/HER2- mBC Population | Percentage of Participants Who Permanently Discontinued Sacituzumab Govitecan-hziy (SG) Due to Any Adverse Events, Excluding Adverse Events Leading to Death | 5.6 Percentage of participants |
| mUC Population | Percentage of Participants Who Permanently Discontinued Sacituzumab Govitecan-hziy (SG) Due to Any Adverse Events, Excluding Adverse Events Leading to Death | 15.6 Percentage of participants |
| Overall Safety Population (OSP) | Percentage of Participants Who Permanently Discontinued Sacituzumab Govitecan-hziy (SG) Due to Any Adverse Events, Excluding Adverse Events Leading to Death | 8.1 Percentage of participants |
Primary
Percentage of Participants Who Required Dose Interruption Due to Any Adverse Events
Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP).
Time frame: First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)
Population: * Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease \& who received at least 1 dose of 10 mg/kg SG~* HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy \& who received at least 1 dose of 10 mg/kg SG~* mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments \& who received at least 1 dose of 10 mg/kg SG~* OSP: All participants who received at least 1 dose of SG
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TNBC Target Population | Percentage of Participants Who Required Dose Interruption Due to Any Adverse Events | 45.4 Percentage of participants |
| HR+/HER2- mBC Population | Percentage of Participants Who Required Dose Interruption Due to Any Adverse Events | 46.3 Percentage of participants |
| mUC Population | Percentage of Participants Who Required Dose Interruption Due to Any Adverse Events | 51.1 Percentage of participants |
| Overall Safety Population (OSP) | Percentage of Participants Who Required Dose Interruption Due to Any Adverse Events | 51.7 Percentage of participants |
Secondary
Clinical Benefit Rate (CBR) by Local Assessment
Clinical benefit rate (CR+PR+\[stable disease (SD) ≥ 6 months\]) is defined as those participants with best response as CR or PR or else SD with a duration of at least 6 months. SD for 6 months duration was defined as the time from the first dose to the first documentation of PD or to the last adequate response assessment prior to data cut-off date, whichever is earlier. Per planned analysis, CBR by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time frame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
Population: * Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease \& who received at least 1 dose of 10 mg/kg SG~* HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy \& who received at least 1 dose of 10 mg/kg SG~* mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments \& who received at least 1 dose of 10 mg/kg SG
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TNBC Target Population | Clinical Benefit Rate (CBR) by Local Assessment | 45.4 Percentage of participants |
| HR+/HER2- mBC Population | Clinical Benefit Rate (CBR) by Local Assessment | 44.4 Percentage of participants |
| mUC Population | Clinical Benefit Rate (CBR) by Local Assessment | 44.4 Percentage of participants |
Secondary
Duration of Response by ICR
Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only.
Time frame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
Population: Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease and who received SG at a dose of 10 mg/kg. Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TNBC Target Population | Duration of Response by ICR | 9.1 months |
Secondary
Duration of Response by Local Assessment
Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Per planned analysis, duration of response by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time frame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
Population: * Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease \& who received at least 1 dose of 10 mg/kg SG~* HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy \& who received at least 1 dose of 10 mg/kg SG~* mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments \& who received at least 1 dose of 10 mg/kg SG
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TNBC Target Population | Duration of Response by Local Assessment | 7.7 months |
| HR+/HER2- mBC Population | Duration of Response by Local Assessment | 8.7 months |
| mUC Population | Duration of Response by Local Assessment | 12.9 months |
Secondary
Overall Survival by Local Assessment
Overall survival was defined as the time from the date of the first dose start date to the date of death due to any cause. Per planned analysis, overall survival by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time frame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
Population: * Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease \& who received at least 1 dose of 10 mg/kg SG~* HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy \& who received at least 1 dose of 10 mg/kg SG~* mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments \& who received at least 1 dose of 10 mg/kg SG
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TNBC Target Population | Overall Survival by Local Assessment | 13.0 months |
| HR+/HER2- mBC Population | Overall Survival by Local Assessment | 12.0 months |
| mUC Population | Overall Survival by Local Assessment | 16.8 months |
Secondary
Pharmacokinetic (PK) Parameter: T1/2 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
T1/2 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. T1/2 is defined as apparent terminal elimination half-life (h); calculated as 0.693/λz. The dose level evaluated for PK analysis was 10 mg/kg.
Time frame: Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hours (± 30 minutes) for subsequent infusions
Population: Participants with epithelial cancer that involved any one of the following with available data were analyzed: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head \& neck cancers- squamous cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non TNBC, TNBC and mUC.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TNBC Target Population | Pharmacokinetic (PK) Parameter: T1/2 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Total Antibody | 66.6 hours | Geometric Coefficient of Variation 14.4 |
| TNBC Target Population | Pharmacokinetic (PK) Parameter: T1/2 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | SN-38G | 21.4 hours | Geometric Coefficient of Variation 24.5 |
| TNBC Target Population | Pharmacokinetic (PK) Parameter: T1/2 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Total SN-38 | 20.2 hours | Geometric Coefficient of Variation 26.6 |
| TNBC Target Population | Pharmacokinetic (PK) Parameter: T1/2 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Sacituzumab Govitecan-hziy (SG) | 15.0 hours | Geometric Coefficient of Variation 15.3 |
| TNBC Target Population | Pharmacokinetic (PK) Parameter: T1/2 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Free SN-38 | 17.1 hours | Geometric Coefficient of Variation 18.6 |
Secondary
PK Parameter: AUC0-168 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
AUC0-168 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-168 is defined as area under the serum concentration-time curve from time 0 to 168 hours. The dose level evaluated for PK analysis was 10 mg/kg.
Time frame: Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions
Population: Participants with epithelial cancer that involved any one of the following with available data were analyzed: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head \& neck cancers- squamouse cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non TNBC, TNBC and mUC.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TNBC Target Population | PK Parameter: AUC0-168 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Total Antibody | 20800 microgram*hour per liter | Geometric Coefficient of Variation 22.2 |
| TNBC Target Population | PK Parameter: AUC0-168 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | SN-38G | 0.842 microgram*hour per liter | Geometric Coefficient of Variation 50 |
| TNBC Target Population | PK Parameter: AUC0-168 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Total SN-38 | 107 microgram*hour per liter | Geometric Coefficient of Variation 25.4 |
| TNBC Target Population | PK Parameter: AUC0-168 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Sacituzumab Govitecan-hziy (SG) | 5050 microgram*hour per liter | Geometric Coefficient of Variation 24.4 |
| TNBC Target Population | PK Parameter: AUC0-168 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Free SN-38 | 3.08 microgram*hour per liter | Geometric Coefficient of Variation 56.6 |
Secondary
PK Parameter: AUC0-24 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
AUC0-24 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-24 is defined as area under the serum concentration-time curve from time 0 to 24 hours. The dose level evaluated for PK analysis was 10 mg/kg.
Time frame: Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions
Population: Participants with epithelial cancer that involved any one of the following with available data were analyzed: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head \& neck cancers- squamouse cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non TNBC, TNBC and mUC.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TNBC Target Population | PK Parameter: AUC0-24 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Total Antibody | 4940 microgram*hour per liter | Geometric Coefficient of Variation 30.1 |
| TNBC Target Population | PK Parameter: AUC0-24 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | SN-38G | 0.370 microgram*hour per liter | Geometric Coefficient of Variation 45.6 |
| TNBC Target Population | PK Parameter: AUC0-24 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Total SN-38 | 65.5 microgram*hour per liter | Geometric Coefficient of Variation 29.2 |
| TNBC Target Population | PK Parameter: AUC0-24 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Sacituzumab Govitecan-hziy (SG) | 3290 microgram*hour per liter | Geometric Coefficient of Variation 25.2 |
| TNBC Target Population | PK Parameter: AUC0-24 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Free SN-38 | 1.67 microgram*hour per liter | Geometric Coefficient of Variation 58.5 |
Secondary
PK Parameter: AUC0-inf of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
AUC0-inf was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-inf is defined as area under the serum concentration-time curve from time 0 extrapolated to infinity. The dose level evaluated for PK analysis was 10 mg/kg.
Time frame: Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions
Population: Participants with epithelial cancer that involved any one of the following with available data were analyzed: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head \& neck cancers- squamouse cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non TNBC, TNBC and mUC.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TNBC Target Population | PK Parameter: AUC0-inf of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Total Antibody | 25100 microgram*hour per liter | Geometric Coefficient of Variation 20.5 |
| TNBC Target Population | PK Parameter: AUC0-inf of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | SN-38G | 0.850 microgram*hour per liter | Geometric Coefficient of Variation 50.7 |
| TNBC Target Population | PK Parameter: AUC0-inf of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Total SN-38 | 107 microgram*hour per liter | Geometric Coefficient of Variation 25.5 |
| TNBC Target Population | PK Parameter: AUC0-inf of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Sacituzumab Govitecan-hziy (SG) | 5050 microgram*hour per liter | Geometric Coefficient of Variation 24.4 |
| TNBC Target Population | PK Parameter: AUC0-inf of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Free SN-38 | 3.08 microgram*hour per liter | Geometric Coefficient of Variation 56.6 |
Secondary
PK Parameter: Cmax of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
Cmax was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. Cmax is defined as maximum observed serum concentration obtained directly from the observed concentration-time data. The dose level evaluated for PK analysis was 10 mg/kg.
Time frame: Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions
Population: Participants with epithelial cancer that involved any one of the following with available data were analyzed: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head \& neck cancers- squamouse cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non TNBC, TNBC and mUC.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| TNBC Target Population | PK Parameter: Cmax of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Total Antibody | 245 microgram per liter | Geometric Coefficient of Variation 26.9 |
| TNBC Target Population | PK Parameter: Cmax of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | SN-38G | 0.0206 microgram per liter | Geometric Coefficient of Variation 50.4 |
| TNBC Target Population | PK Parameter: Cmax of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Total SN-38 | 4.39 microgram per liter | Geometric Coefficient of Variation 25.2 |
| TNBC Target Population | PK Parameter: Cmax of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Sacituzumab Govitecan-hziy (SG) | 220 microgram per liter | Geometric Coefficient of Variation 24.7 |
| TNBC Target Population | PK Parameter: Cmax of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 | Free SN-38 | 0.0992 microgram per liter | Geometric Coefficient of Variation 61.1 |
Secondary
Progression Free Survival (PFS) by Local Assessment
Progression-free survival (PFS) was defined as the interval from the first dose start date to the date of disease progression defined as documented progressive disease (PD) or death from any cause, whichever occurs first. Per planned analysis, PFS by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time frame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
Population: * Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease \& who received at least 1 dose of 10 mg/kg SG~* HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy \& who received at least 1 dose of 10 mg/kg SG~* mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments \& who received at least 1 dose of 10 mg/kg SG
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TNBC Target Population | Progression Free Survival (PFS) by Local Assessment | 5.6 months |
| HR+/HER2- mBC Population | Progression Free Survival (PFS) by Local Assessment | 5.5 months |
| mUC Population | Progression Free Survival (PFS) by Local Assessment | 6.8 months |
Secondary
Time to Response by ICR
Time to response was defined as the time from the first dose to the first documentation of response (PR or CR). Per planned analysis, time to response by ICR was assessed for the TNBC Target Population only.
Time frame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
Population: Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease \& who received at least 1 dose of 10 mg/kg SG
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TNBC Target Population | Time to Response by ICR | 2.2 months |
Secondary
Time to Response by Local Assessments
Time to response was defined as the time from the first dose to the first documentation of response (PR or CR). Per planned analysis, time to response by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time frame: Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)
Population: * Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease \& who received at least 1 dose of 10 mg/kg SG~* HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy \& who received at least 1 dose of 10 mg/kg SG~* mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments \& who received at least 1 dose of 10 mg/kg SG
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TNBC Target Population | Time to Response by Local Assessments | 2.0 months |
| HR+/HER2- mBC Population | Time to Response by Local Assessments | 2.1 months |
| mUC Population | Time to Response by Local Assessments | 1.9 months |