Study of Sacituzumab Govitecan (SG) in Japanese Participants With Advanced Solid Tumors (ASCENT-J02)

A Phase 1/2 Open-Label Study of Sacituzumab Govitecan in Japanese Patients With Advanced Solid Tumors (ASCENT-J02)

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 Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor; Metastatic Urothelial Cancer; Metastatic Triple-Negative Breast Cancer; HR+/HER2- Metastatic Breast Cancer
• Intervention / Treatment: Drug: Sacituzumab Govitecan-hziy

• Study Type: Interventional
• Enrollment (Estimated): 143
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Gilead Clinical Study Information Center; Phone Number: 1-833-445-3230 (GILEAD-0); Email: GileadClinicalTrials@gilead.com

Study Locations

• Japan
  • Aichi, Japan, 464-8681
    • Recruiting
    • Aichi Cancer Center Hospital
  • Akita, Japan, 010-8543
    • Recruiting
    • Akita University Hospital
  • Aoba-ku, Japan, 980-8574
    • Recruiting
    • Tohoku University Hospital
  • Aomori, Japan, 036-8563
    • Recruiting
    • Hirosaki University Hospital
  • Asahi-ku, Japan, 241-8515
    • Recruiting
    • Kanagawa Cancer Center
  • Bunkyo-ku, Japan, 113-8431
    • Recruiting
    • Juntendo University Hospital
  • Chiba, Japan, 277-8577
    • Recruiting
    • National Cancer Center Hospital East
  • Chiba, Japan, 260-8717
    • Recruiting
    • Chiba Cancer Center
  • Chuo-ku, Japan, 540-0006
    • Recruiting
    • Nagoya University Hospital
  • Chuo-ku, Japan, 541-8567
    • Recruiting
    • Osaka International Cancer Institute
  • Chuo-ku, Japan, 260-8717
    • Recruiting
    • Chiba Cancer
  • Ehime, Japan, 791-0280
    • Recruiting
    • National Hospital Organization Shikoku Cancer Center
  • Ehime, Japan, 791-0245
    • Recruiting
    • Shikoku Cancer Center
  • Hyogo, Japan, 673-8558
    • Recruiting
    • Hyogo Cancer Center
  • Kagawa, Japan, 761-0793
    • Recruiting
    • Kagawa University Hospital
  • Kanagawa, Japan, 259-1193
    • Recruiting
    • Tokai University School of Medicine
  • Koto, Japan, 135-8550
    • Recruiting
    • The Cancer Institute Hospital of Jfcr
  • Kumamoto- shi, Japan, 860-8556
    • Recruiting
    • Kumamoto University Hospital
  • Minami-ku, Japan, 734-8551
    • Recruiting
    • Hiroshima University Hospital
  • Nara, Japan, 634-8522
    • Recruiting
    • Nara Medical University Hospital
  • Nishinomiya-shi, Japan, 663-8501
    • Recruiting
    • Hyogo College of Medicine College Hospital
  • Okayama, Japan, 700-8558
    • Recruiting
    • Okayama University Hospital
  • Osaka, Japan, 565-0871
    • Recruiting
    • Osaka University Hospital
  • Osaka, Japan, 545-0051
    • Recruiting
    • Osaka Metropolitan University Hospital
  • Osaka, Japan, 577-8502
    • Recruiting
    • Kindai University Hospital
  • Osakasayama-shi, Japan, 589-8511
    • Recruiting
    • Kindai University Hospital
  • Saitama, Japan, 350-1298
    • Recruiting
    • Saitama Medical University
  • Sakyo-ku, Japan, 606-8507
    • Recruiting
    • Kyoto University Hospital
  • Sapporo, Japan, 003-0804
    • Recruiting
    • National Hospital Organization Hokkaido Cancer Center
  • Shinjuku-ku, Japan, 162-8655
    • Recruiting
    • National Center for Global Health and Medicine
  • Tokyo, Japan, 104-0045
    • Recruiting
    • National Cancer Center Hospital
  • Tokyo, Japan, 1608582
    • Recruiting
    • Keio University Hospital
  • Tokyo, Japan, 142-8555
    • Recruiting
    • Showa University Hospital
  • Tokyo, Japan, 113-8519
    • Recruiting
    • Tokyo Medical And Dental University, Medical Hospital
  • Yamaguchi, Japan, 755-0046
    • Recruiting
    • Yamaguchi University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sacituzumab Govitecan-hziy 8 mg, Advanced Solid Tumors; (Phase 1 Cohort A: dose escalation) Japanese participants with advanced solid tumors will receive SG 8 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy; Administered intravenously (IV); Other Names: IMMU-132; GS-0132; Trodelvy™
Experimental: Sacituzumab Govitecan-hziy 10 mg, Advanced Solid Tumors; (Phase 1 Cohort A: dose escalation) Japanese participants with advanced solid tumors will receive SG 10 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy; Administered intravenously (IV); Other Names: IMMU-132; GS-0132; Trodelvy™
Experimental: Sacituzumab Govitecan-hziy 6 mg, UGT1A1 Polymorphism; (Phase 1 Cohort B: dose escalation) Japanese participants with UGT1A1 polymorphism will receive SG 6 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy; Administered intravenously (IV); Other Names: IMMU-132; GS-0132; Trodelvy™
Experimental: Sacituzumab Govitecan-hziy 8 mg, UGT1A1 Polymorphism; (Phase 1 Cohort B: dose escalation) Japanese participants with UGT1A1 polymorphism will receive SG 8 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy; Administered intravenously (IV); Other Names: IMMU-132; GS-0132; Trodelvy™
Experimental: Sacituzumab Govitecan-hziy 10 mg, UGT1A1 Polymorphism; (Phase 1 Cohort B: dose escalation) Japanese participants with UGT1A1 polymorphism will receive SG 10 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy; Administered intravenously (IV); Other Names: IMMU-132; GS-0132; Trodelvy™
Experimental: Sacituzumab Govitecan-hziy 6 mg, Advanced Solid Tumors; (Phase 1 Cohort A: dose escalation) Japanese participants with advanced solid tumors will receive sacituzumab govitecan-hziy (SG) 6 mg/kg by intravenous (IV) injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy; Administered intravenously (IV); Other Names: IMMU-132; GS-0132; Trodelvy™
Experimental: Sacituzumab Govitecan-hziy, Metastatic Triple-negative Breast Cancer (mTNBC); (Phase 2: dose expansion) Japanese participants with mTNBC will receive SG at the recommended Phase 2 dose (RP2D) on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy; Administered intravenously (IV); Other Names: IMMU-132; GS-0132; Trodelvy™
Experimental: Sacituzumab Govitecan-hziy, HR+/HER2- Metastatic Breast Cancer (HR+/HER2- mBC); (Phase 2) Japanese participants with HR+/HER2- mBC will receive SG at the recommended Phase 2 dose (RP2D) on Day 1 and Day 8 of a 21 day cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy; Administered intravenously (IV); Other Names: IMMU-132; GS-0132; Trodelvy™
Experimental: Sacituzumab Govitecan-hziy, Metastatic Urothelial Carcinoma (mUC); (Phase 2) Japanese participants with mUC will receive SG at the recommended Phase 2 dose (RP2D) on Day 1 and Day 8 of a 21 day cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy; Administered intravenously (IV); Other Names: IMMU-132; GS-0132; Trodelvy™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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 (RECIST v1.1)	Up to 17 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 33 months
Phase 1:PK parameters Tmax of SG and Free SN-38	Tmax is defined as time (observed time point) of Cmax	Up to 33 months
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.	Up to 33 months
Phase 1: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) Against SG		Up to 33 months
Phase 2: 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: 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: ORR Assessed by Investigator	ORR is defined as the proportion of participants who achieve a CR or PR as assessed by RECIST v1.1.	Up to 17 months
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.	Up to 33 months
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.	Up to 17 months
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.	Up to 33 months
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.	Up to 33 months
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.	Up to 33 months
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.	Up to 33 months
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.	Up to 17 months

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2021
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: October 19, 2021
• First Submitted That Met QC Criteria: October 19, 2021
• First Posted (Actual): November 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunoconjugates; Sacituzumab govitecan
• Other Study ID Numbers: GS-US-569-6172; jRCT2031210346 (Registry Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes