Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer

JRCT ID: jRCT2041220123

Registered date:22/01/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Triple Negative Breast Cancer / PD-L1 Positive
• Date of first enrollment: 14/02/2023
• Target sample size: 440
• Countries of recruitment: Hong Kong,Japan,Puerto Rico,Japan,United States,Japan,Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,Chile,Japan,Czechia,Japan,France,Japan,Germany,Japan,Hungary,Japan,Israel,Japan,Italy,Japan,Korea,Japan,Republic of Mexico,Japan,Netherlands,Japan,Poland,Japan,South Africa,Japan,Spain,Japan,Switzerland,Japan,Taiwan,Japan,Turkey,Japan,United Kingdom,Japan,Malaysia,Japan,Singapore,Japan
• Study type: Interventional

Intervention(s)

Patients meeting eligibility will be randomly assigned (1:1) to one of 2 arms:
Arm A: Sacituzumab Govitecan 10 mg/kg intravenously on Days 1 and 8 of 21-day cycles and pembrolizumab 200 mg on Day 1 of 21-day cycles
Arm B: TPC (21 or 28-day cycles) and pembrolizumab 200 mg on Day 1 of 21-day cycles

Treatment of physician's choice which will be selected prior to randomization from one of the 3 allowed regimens:
Paclitaxel 90 mg/m^2 intravenously on Days 1, 8, and 15 of 28-day cycles; or
nab-Paclitaxel 100 mg/m^2 intravenously on Days 1, 8, and 15 of 28-day cycles; or
Gemcitabine 1000 mg/m^2 intravenously plus carboplatin AUC 2 intravenously on Days 1 and 8 of 21-day cycles.

No other treatment regimen is permitted and no combination or crossovers of the 3 choices are permitted. Body surface area dosing (mg/m^2) is based upon body surface area per local standard of care.

Outcome(s)

Primary Outcome

1. Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS is defined as the time from the date of randomization until the date of objective progressive disease (PD) or death (whichever comes first).
[Time Frame: Randomization up to approximately 33 months]

Secondary Outcome

1. Overall Survival (OS)
OS is defined as the time from the date of randomization until death due to any cause.
[Time Frame: Randomization up to approximately 53 months]

2. Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1
ORR is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) that is confirmed at least 4 weeks after initial documentation of response.
[Time Frame: Randomization up to approximately 53 months]

3. Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1
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 (whichever comes first).
[Time Frame: Randomization up to approximately 53 months]

4. Time to Response (TTR) as Assessed by BICR per RECIST Version 1.1
TTR is defined as the time from the date of randomization until the first documentation of CR or PR.
[Time Frame: Randomization up to approximately 53 months]

5. Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
[Time Frame: First dose date up to 53 months plus 30 days]

6. Percentage of Participants Experiencing Clinical Laboratory Abnormalities
[Time Frame: First dose date up to 53 months plus 30 days]

7. Time to Deterioration (TTD) in Global Health Status/Quality of Life (QoL) Scale as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Questionnaire, Version 3.0 (EORTC QLQ-C30)
The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant).
[Time Frame: Randomization up to approximately 53 months]

8. TTD of Pain Score as Measured by EORTC QLQ-C30
The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant).
[Time Frame: Randomization up to approximately 53 months]

9. TTD of Fatigue Score as Measured by EORTC QLQ-C30
The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (ie, a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (ie, a worse state of the participant).
[Time Frame: Randomization up to approximately 53 months]

10. TTD of Physical Functioning Domain Score as Measured by EORTC QLQ-C30
The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (ie, a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (ie, a worse state of the participant).
[Time Frame: Randomization up to approximately 53 months]

11. TTD of Role Functioning Score as Measured by EORTC QLQ-C30
The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (ie, a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (ie, a worse state of the participant).
[Time Frame: Randomization up to approximately 53 months]

Key inclusion & exclusion criteria

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

Include criteria

Individuals with locally advanced, inoperable, or metastatic triple-negative breast cancer (TNBC) who have not received previous systemic therapy for advanced disease and whose tumors are programmed cell death ligand 1 (PD-L1) positive at screening.
-Individuals must have completed treatment for Stage I to III breast cancer, if indicated, and >= 6 months must have elapsed between completion of treatment with curative intent and first documented local or distant disease recurrence.
-Individuals presenting with de novo metastatic TNBC are eligible for this study.
-TNBC status and tumor PD-L1 combined positive score (CPS) will be confirmed centrally on a recent or archival tumor specimen.
-Individuals must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria as evaluated locally.

Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Demonstrates adequate organ function.

Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.

Individuals with HIV must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Exclude criteria

Positive serum pregnancy test or women who are lactating.

Received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor.

Individuals may not have received systemic anticancer treatment within the previous 6 months or radiation therapy within 2 weeks prior to enrollment.

Individuals may not be participating in a study with an investigational agent or investigational device within 4 weeks prior to randomization. Individuals participating in observational studies are eligible.

Have previously received topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor.

Have an active second malignancy.

Have active serious infection requiring antibiotics.

Individuals positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.

Have active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

Has an active autoimmune disease that has required systemic treatment in the past 2 years.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Information

• Primary Sponsor: Iwahori Yuki
• Secondary ID(s): NCT05382286,2021-005742-14