The primary objectives of this study are as follows: Phase 1 (sequential dose-escalation): to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent and to determine the recommended Phase 2 dose (RP2D) of SG in Japanese participants with advance solid tumors. Phase 2: Evaluate the safety and efficacy of SG in Japanese participants with metastatic triple-negative breast cancer (mTNBC), hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC), and metastatic urothelial cancer (mUC).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
135
Administered intravenously (IV)
Aichi Cancer Center Hospital
Aichi, Japan
Akita University Hospital
Akita, Japan
Tohoku University Hospital
Aoba-ku, Japan
Hirosaki University Hospital
Aomori, Japan
Kanagawa Cancer Center
Asahi-ku, Japan
Juntendo University Hospital
Phase 1: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) Defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03
Time frame: First dose date to last dose date (Up to 15 weeks) plus 30 days
Phase 1: Percentage of Participants Experiencing Laboratory Abnormalities Defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03
Time frame: First dose date to last dose date (Up to 15 weeks) plus 30 days
Phase 1: Percentage of Participants Experiencing Dose-limiting toxicity (DLTs) per Dose level
Time frame: First dose date up to 21 days
Phase 2:(Metastatic Triple-negative Breast Cancer (mTNBC);Hormone Receptor-positive/Human Epidermal Growth Factor Receptor 2-negative Metastatic Breast Cancer (HR+/HER2- mBC) Cohorts):Objective Response Rate (ORR) as Assessed by IRC
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR), confirmed at least 4 weeks later as assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by Independent Review Committee (IRC).
Time frame: Up to 17 months
Phase 2 (Metastatic Urothelial Cancer (mUC) Cohort): ORR as Assessed by Investigator
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) confirmed at least 4 weeks later as assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time frame: Up to 17 months
Phase 1: Pharmacokinetic (PK) Parameter: Cmax of Sacituzumab Govitecan-hziy (SG) and Free SN-38
Cmax is defined as the maximum observed concentration of drug
Time frame: Up to 33 months
Phase 1: PK Parameter: Tmax of SG and Free SN-38
Tmax is defined as time (observed time point) of Cmax
Time frame: Up to 33 months
Phase 1: PK Parameter: AUC0-168h of SG and Free SN-38
AUC0-168h is defined as partial area under the concentration of drug over time between 0 to time 168-hour.
Time frame: Up to 33 months
Phase 1 : Percentage of Participants Who Develop Anti-Drug Antibodies (ADAs) Against SG
Time frame: Up to 33 months
Phase 2 (All Cohorts): Percentage of Participants Experiencing TEAEs Defined by NCI CTCAE Version 4.03
Time frame: First dose date to last dose date (Up to 33 months) plus 30 days
Phase 2 (All Cohorts): Percentage of Participants Experiencing Laboratory Abnormalities Defined by NCI CTCAE Version 4.03
Time frame: First dose date to last dose date (Up to 33 months) plus 30 days
Phase 2(All Cohorts): Progression-free survival (PFS) as Assessed by Investigator
PFS is defined as the interval from the first dose of SG to the earlier of the first documentation of objective progressive disease (PD) or death from any cause, whichever comes first.
Time frame: Up to 33 months
Phase 2 (All Cohorts): ORR as Assessed by Investigator
ORR is defined as the proportion of participants who achieve a CR or PR as assessed by RECIST v1.1.
Time frame: Up to 17 months
Phase 2 (All Cohorts): Overall Survival (OS)
OS is defined as the time from date of first dose of SG to death from any cause, whichever comes first.
Time frame: Up to 33 months
Phase 2 (All Cohorts): Duration of Response (DOR) as Assessed by Investigator
DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of objective PD or death from any cause.
Time frame: Up to 33 months
Phase 2 (All Cohorts): Time to response (TTR) as Assessed by Investigator
TTR is defined as the time from first dose of SG to the first documentation of CR or PR.
Time frame: Up to 17 months
Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Progression-free survival (PFS) as Assessed by IRC
PFS is defined as the interval from the first dose of SG to the earlier of the first documentation of objective progressive disease (PD) or death from any cause, whichever comes first.
Time frame: Up to 33 months
Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Duration of Response (DOR) as Assessed by IRC
DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of objective PD or death from any cause.
Time frame: Up to 33 months
Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Time to response (TTR) as Assessed by IRC
TTR is defined as the time from first dose of SG to the first documentation of CR or PR.
Time frame: Up to 17 months
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Bunkyō City, Japan
Chiba Cancer Center
Chiba, Japan
National Cancer Center Hospital East
Chiba, Japan
Chiba Cancer
Chūōku, Japan
Nagoya University Hospital
Chūōku, Japan
...and 26 more locations