Study of Sacituzumab Govitecan in Japanese Patients with Advanced Solid Tumors or Triple-negative Breast Cancer (ASCENT-J02)

JRCT ID: jRCT2031210346

Registered date:28/09/2021

Basic Information

• Recruitment status: Recruiting

Health condition(s) or Problem(s) studied

advanced solid tumors
Metastatic Triple-Negative Breast Cancer
HR+/HER2-Metastatic Breast Cancer

• Date of first enrollment: 09/11/2021
• Target sample size: 143
• Study type: Interventional
• Intervention(s): Sacituzumab govitecan is administered as an IV infusion on Day 1 and Day 8 every 21-day cycles.

Outcome(s)

Primary Outcome

1. 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]
2. 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]
3. Phase 1: Percentage of Participants Experiencing Dose-limiting toxicity (DLTs) per Dose level
[Time Frame: First dose date up to 21 days]
4. Phase 2: Objective Response Rate (ORR) Assessed by Independent Review Committee (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 (RECISTv1.1)
[Time Frame: Up to 17 months]

Secondary Outcome

5. 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]
6. Phase 1:PK parameters Tmax of SG and Free SN-38
Tmax is defined as time (observed time point) of Cmax.
[Time Frame: Up to 33 months]
7. Phase 1:PK parameters 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]
8. Phase 1: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) Against SG
[Time Frame: Up to 33 months]
9. Phase 2: 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]
10. Phase 2: 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]
11. Phase 2: Progression-free survival (PFS) 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]
12. Phase 2: ORR 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]
13. Phase 2: 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]
14. Phase 2: Duration of Response (DOR) 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]
15. Phase 2: Time to response (TTR) 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]
16. Phase 2: Progression-free survival (PFS) 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]
17. Phase 2: Duration of Response (DOR) 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]
18. Phase 2: Time to response (TTR) 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]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Eastern Cooperative Oncology Group (ECOG) performance status =< 1
2) Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST Version 1.1 criteria
3) Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation
4) Adequate hepatic function (bilirubin =< 1.5 upper limit of normal [ULN]), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 ULN
5) Creatinine clearance >= 30 mL/min
6) Male patients and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
7) 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.
8) Phase 2 metastatic triple-negative breast cancer (mTNBC) Cohort: Histologicallyor 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.
9) Phase 2 hormone receptor-positive/human epidermal growth factor receptor2-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 metastatic disease.
10) 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.

Exclude criteria

1) Positive serum pregnancy test, or females who may possibly be pregnant
2) Known Gilbert's disease
3) Have previously received antibody drug conjugate containing topoisomerase I inhibitors
4) Presence of bulky disease (defined as any single mass > 7 cm in greatest dimention).
5) Known to be HIV positive, or hepatitis B virus (HBV) surface antigen positive or hepatitis C virus (HCV) antibody positive at screening.
6) Known history of significant cardiac disease
7) Known history of clinically significant active chronic obstructive pulmonary disease, or other moderate-to-severe chronic respiratory illness
8) History of interstitial lung disease.
9) History of clinically significant gastrointestinal (GI) bleeding, have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation
10) Individuals with a history of anaphylactic reaction to irinotecan

Related Information

• Primary Sponsor: Iwahori Yuki
• Secondary ID(s): NCT05101096