Advanced Solid Tumor, HR+/HER2- Metastatic Breast Cancer, Metastatic Triple-Negative Breast Cancer, Metastatic Urothelial Cancer
Conditions
Brief summary
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).
Interventions
DRUGSacituzumab Govitecan-hziy
Administered intravenously (IV)
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
Key Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 * Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST Version 1.1 criteria * Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation * Adequate hepatic function (bilirubin ≤ 1.5 upper limit of normal (ULN)), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ULN * Creatinine clearance ≥ 30 mL/min * Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception. * Phase 1 only: Histologically or cytologically confirmed advanced solid tumor that is refractory to or intolerant of all standard therapy or for which no standard therapy is available. * Phase 2 metastatic triple-negative breast cancer (mTNBC) Cohort: Histologically or cytologically confirmed TNBC per American Society of Clinical Oncologists/College of American Pathologists (ASCO/CAP) criteria, based on the most recent analyzed biopsy or other pathology specimen. Refractory to or relapsed after at least 2 prior standard-of-care chemotherapy regimens for unresectable, locally advanced or metastatic breast cancer. * Phase 2 hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (HR+/HER2- mBC) Cohort: Documented evidence of HR+/HER2- mBC confirmed by a local laboratory and defined per ASCO/CAP criteria. * Refractory to or relapsed after 2 prior systemic chemotherapy regimens for locally advanced unresectable or metastatic disease. * Phase 2 metastatic urothelial cancer (mUC) Cohort: Histologically documented UC that is metastatic or locally advanced unresectable. * Progressed or recurred following receipt of platinum-containing regimen and anti-PD-1/PD-L1 therapy for metastatic or locally advanced unresectable disease Key
Exclusion criteria
* Positive serum pregnancy test, or females who may possibly be pregnant * Known Gilbert's disease * Have previously received antibody drug conjugate containing topoisomerase I inhibitors * Presence of bulky disease (defined as any single mass \> 7 cm in greatest dimension). * Known to be HIV positive, or hepatitis B virus (HBV) surface antigen positive or hepatitis C virus (HCV) antibody positive at screening * Known history of significant cardiac disease * Known history of clinically significant active chronic obstructive pulmonary disease, or other moderate-to-severe chronic respiratory illness * History of interstitial lung disease * History of clinically significant gastrointestinal (GI) bleeding, have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation * Individuals with a history of anaphylactic reaction to irinotecan. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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 | 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 | Up to 17 months | 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). |
| Phase 2 (Metastatic Urothelial Cancer (mUC) Cohort): ORR as Assessed by Investigator | Up to 17 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Pharmacokinetic (PK) Parameter: Cmax of Sacituzumab Govitecan-hziy (SG) and Free SN-38 | Up to 33 months | Cmax is defined as the maximum observed concentration of drug |
| Phase 1: PK Parameter: Tmax of SG and Free SN-38 | Up to 33 months | Tmax is defined as time (observed time point) of Cmax |
| Phase 1: PK Parameter: AUC0-168h of SG and Free SN-38 | Up to 33 months | AUC0-168h is defined as partial area under the concentration of drug over time between 0 to time 168-hour. |
| Phase 1 : Percentage of Participants Who Develop Anti-Drug Antibodies (ADAs) Against SG | Up to 33 months | — |
| Phase 2 (All Cohorts): Percentage of Participants Experiencing TEAEs Defined by NCI CTCAE Version 4.03 | 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 | 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 | Up to 33 months | 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. |
| Phase 2 (All Cohorts): ORR as Assessed by Investigator | Up to 17 months | ORR is defined as the proportion of participants who achieve a CR or PR as assessed by RECIST v1.1. |
| Phase 2 (All Cohorts): Overall Survival (OS) | Up to 33 months | OS is defined as the time from date of first dose of SG to death from any cause, whichever comes first. |
| Phase 2 (All Cohorts): Duration of Response (DOR) as Assessed by Investigator | Up to 33 months | 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. |
| Phase 2 (All Cohorts): Time to response (TTR) as Assessed by Investigator | Up to 17 months | TTR is defined as the time from first dose of SG to the first documentation of CR or PR. |
| Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Progression-free survival (PFS) as Assessed by IRC | Up to 33 months | 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. |
| Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Duration of Response (DOR) as Assessed by IRC | Up to 33 months | 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. |
| Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Time to response (TTR) as Assessed by IRC | Up to 17 months | TTR is defined as the time from first dose of SG to the first documentation of CR or PR. |
Countries
Japan
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed