Clinical trial NCT05101096: Study of Sacituzumab Govitecan (SG) in Japanese Participants With Advanced Solid Tumors
Official title: A Phase 1/2 Open-Label Study of Sacituzumab Govitecan in Japanese Patients With Advanced Solid Tumors (ASCENT-J02)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Metastatic Triple-Negative Breast Cancer
HR+/HER2- Metastatic Breast Cancer
Metastatic Urothelial Cancer
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2021-11-01
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility 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/Exclusion criteria may apply.

Primary outcomes:
measure: 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
timeFrame: First dose date to last dose date (Up to 15 weeks) plus 30 days
measure: 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
timeFrame: First dose date to last dose date (Up to 15 weeks) plus 30 days
measure: Phase 1: Percentage of Participants Experiencing Dose-limiting toxicity (DLTs) per Dose level
timeFrame: First dose date up to 21 days
measure: 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
timeFrame: Up to 17 months
measure: Phase 2 (Metastatic Urothelial Cancer (mUC) Cohort): ORR as Assessed by Investigator
timeFrame: Up to 17 months
Secondary outcomes:
measure: Phase 1: Pharmacokinetic (PK) Parameter: Cmax of Sacituzumab Govitecan-hziy (SG) and Free SN-38
timeFrame: Up to 33 months
measure: Phase 1: PK Parameter: Tmax of SG and Free SN-38
timeFrame: Up to 33 months
measure: Phase 1: PK Parameter: AUC0-168h of SG and Free SN-38
timeFrame: Up to 33 months
measure: Phase 1 : Percentage of Participants Who Develop Anti-Drug Antibodies (ADAs) Against SG
timeFrame: Up to 33 months
measure: Phase 2 (All Cohorts): Percentage of Participants Experiencing TEAEs Defined by NCI CTCAE Version 4.03
timeFrame: First dose date to last dose date (Up to 33 months) plus 30 days
measure: Phase 2 (All Cohorts): Percentage of Participants Experiencing Laboratory Abnormalities Defined by NCI CTCAE Version 4.03
timeFrame: First dose date to last dose date (Up to 33 months) plus 30 days
measure: Phase 2(All Cohorts): Progression-free survival (PFS) as Assessed by Investigator
timeFrame: Up to 33 months
measure: Phase 2 (All Cohorts): ORR as Assessed by Investigator
timeFrame: Up to 17 months
measure: Phase 2 (All Cohorts): Overall Survival (OS)
timeFrame: Up to 33 months
measure: Phase 2 (All Cohorts): Duration of Response (DOR) as Assessed by Investigator
timeFrame: Up to 33 months
measure: Phase 2 (All Cohorts): Time to response (TTR) as Assessed by Investigator
timeFrame: Up to 17 months
measure: Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Progression-free survival (PFS) as Assessed by IRC
timeFrame: Up to 33 months
measure: Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Duration of Response (DOR) as Assessed by IRC
timeFrame: Up to 33 months
measure: Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Time to response (TTR) as Assessed by IRC
timeFrame: Up to 17 months
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Akita
country: Japan
facility: Akita University Hospital
city: Aoba-ku
country: Japan
facility: Tohoku University Hospital
city: Aomori
country: Japan
facility: Hirosaki University Hospital
city: Asahi-ku
country: Japan
facility: Kanagawa Cancer Center
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Chuo-ku
country: Japan
facility: Chiba Cancer
city: Chuo-ku
country: Japan
facility: Nagoya University Hospital
city: Chuo-ku
country: Japan
facility: Osaka International Cancer Institute
city: Ehime
country: Japan
facility: Shikoku Cancer Center
city: Ehime
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
city: Hyogo
country: Japan
facility: Hyogo Cancer Center
city: Kagawa
country: Japan
facility: Kagawa University Hospital
city: Kanagawa
country: Japan
facility: Tokai University School of Medicine
city: Koto
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Kumamoto- shi
country: Japan
facility: Kumamoto University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Minami-ku
country: Japan
facility: Hiroshima University Hospital
city: Nara
country: Japan
facility: Nara Medical University Hospital
city: Nishinomiya-shi
country: Japan
facility: Hyogo College of Medicine College Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osakasayama-shi
country: Japan
facility: Kindai University Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Saitama
country: Japan
facility: Saitama Medical University
city: Sapporo
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
city: Shinjuku-ku
country: Japan
facility: National Center for Global Health and Medicine
city: Tokyo
country: Japan
facility: National Cancer Center hospital
city: Tokyo
country: Japan
facility: Tokyo Medical And Dental University, Medical Hospital
city: Tokyo
country: Japan
facility: Showa University Hospital
city: Tokyo
country: Japan
facility: Keio University Hospital
city: Yamaguchi
country: Japan
facility: Yamaguchi University Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: