Description:
The primary objective of this study is to compare the efficacy of sacituzumab govitecan to
the treatment of physician's choice (TPC) as measured by independently-reviewed Independent
Review Committee (IRC) progression-free survival (PFS) in participants with locally advanced
or metastatic triple-negative breast cancer (TNBC) previously treated with at least two
systemic chemotherapy regimens for unresectable, locally advanced or metastatic disease, and
without brain metastasis at baseline.
Title
- Brief Title: Trial of Sacituzumab Govitecan in Participants With Refractory/Relapsed Metastatic Triple-Negative Breast Cancer Triple-Negative Breast Cancer
- Official Title: An International, Multi-Center, Open-Label, Randomized, Phase III Trial of Sacituzumab Govitecan Versus Treatment of Physician Choice in Patients With Metastatic Triple-Negative Breast Cancer Who Received at Least Two Prior Treatments
Clinical Trial IDs
- ORG STUDY ID:
IMMU-132-05
- SECONDARY ID:
2017-003019-21
- NCT ID:
NCT02574455
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Sacituzumab govitecan | IMMU-132, Trodelvy® | Sacituzumab Govitecan |
Eribulin | Halaven | Treatment of Physician's Choice (TPC) |
Capecitabine | Xeloda | Treatment of Physician's Choice (TPC) |
Gemcitabine | Gemzar | Treatment of Physician's Choice (TPC) |
Vinorelbine | Navelbine | Treatment of Physician's Choice (TPC) |
Purpose
The primary objective of this study is to compare the efficacy of sacituzumab govitecan to
the treatment of physician's choice (TPC) as measured by independently-reviewed Independent
Review Committee (IRC) progression-free survival (PFS) in participants with locally advanced
or metastatic triple-negative breast cancer (TNBC) previously treated with at least two
systemic chemotherapy regimens for unresectable, locally advanced or metastatic disease, and
without brain metastasis at baseline.
Trial Arms
Name | Type | Description | Interventions |
---|
Sacituzumab Govitecan | Experimental | Participants will receive sacituzumab govitecan on Days 1 and 8 of a 21-day treatment cycle. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable adverse events (AEs). | |
Treatment of Physician's Choice (TPC) | Active Comparator | Participants will receive TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent regimen that is selected by the investigator before participant randomization. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable AEs. | - Eribulin
- Capecitabine
- Gemcitabine
- Vinorelbine
|
Eligibility Criteria
Key Inclusion Criteria:
- Histologically or cytologically confirmed TNBC based on the most recent analyzed
biopsy or other pathology specimen. Triple negative is defined as <1% expression for
estrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal
growth factor receptor 2 (HER2) by in-situ hybridization.
- Refractory to or relapsed after at least two prior standard therapeutic regimens for
advanced/metastatic TNBC.
- Prior exposure to a taxane in localized or advanced/metastatic setting.
- Eligible for one of the chemotherapy options listed as TPC (eribulin, capecitabine,
gemcitabine, or vinorelbine) as per investigator assessment.
- Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 .
- Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as
per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Bone-only
disease is not permitted.
- At least 2 weeks beyond prior anti-cancer treatment (chemotherapy, endocrine therapy,
radiotherapy, and/or major surgery), and recovered from all acute toxicities to Grade
1 or less (except alopecia and peripheral neuropathy).
- At least 2 weeks beyond high dose systemic corticosteroids (however, low dose
corticosteroids < 20 mg prednisone or equivalent daily are permitted provided the dose
is stable for 4 weeks).
- Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL,
absolute neutrophil count (ANC) > 1,500 per mm^3, platelets > 100,000 per mm^3).
- Adequate renal and hepatic function (creatinine clearance [CrCL] > 60 mL/min,
bilirubin ≤ 1.5 institutional upper limit of normal [IULN], aspartate aminotransferase
[AST] and alanine aminotransferase [ALT] ≤ 2.5 x IULN or ≤ 5 x IULN if known liver
metastases and serum albumin ≥3 g/dL).
- Recovered from all toxicities to Grade 1 or less by National Cancer Institute common
terminology criteria for adverse events (NCI CTCAE) v4.03 (except alopecia or
peripheral neuropathy that may be Grade 2 or less) at the time of randomization.
Participants with Grade 2 neuropathy are eligible but may not receive vinorelbine as
TPC.
- Participants with treated, non-progressive brain metastases, off high-dose steroids
(>20 mg prednisone or equivalent) for at least 4 weeks can be enrolled in the trial.
Key Exclusion Criteria:
- Women who are pregnant or lactating.
- Women of childbearing potential or fertile men unwilling to use effective
contraception during study and up to three months after treatment discontinuation in
women of child-bearing potential and six months in males post last study drug.
- Participants with Gilbert's disease.
- Participants with non-melanoma skin cancer or carcinoma in situ of the cervix are
eligible, while participants with other prior malignancies must have had at least a
3-year disease-free interval.
- Participants known to be human immunodeficiency (HIV) positive, hepatitis B positive,
or hepatitis C positive.
- Infection requiring antibiotic use within one week of randomization.
- Other concurrent medical or psychiatric conditions that, in the Investigator's
opinion, may be likely to confound study interpretation or prevent completion of study
procedures and follow-up examinations.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-Free Survival (PFS) by Independent Review Committee (IRC) Assessment in Brain Metastasis Negative (BM-ve) Population |
Time Frame: | From randomization until objective tumor progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 22.87 months) |
Safety Issue: | |
Description: | PFS was defined as the time from randomization until objective tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death, whichever came first. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (+20%) in the sum of the target lesions or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate. |
Secondary Outcome Measures
Measure: | Progression-Free Survival (PFS) by IRC Assessment in the ITT Population |
Time Frame: | From randomization until objective tumor progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 22.87 months) |
Safety Issue: | |
Description: | PFS was defined as the time from randomization until objective tumor progression by RECIST v1.1 or death, whichever came first. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (+20%) in the sum of the target lesions or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate. |
Measure: | Overall Survival (OS) in BM-ve Population |
Time Frame: | From the start of study treatment to death from any cause (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 22.87 months) |
Safety Issue: | |
Description: | Overall survival (OS) was defined as the time from the start of study treatment to death from any cause. OS was estimated using Kaplan-Meier estimate. |
Measure: | Overall Survival (OS) in ITT Population |
Time Frame: | From the start of study treatment to death from any cause (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 22.87 months) |
Safety Issue: | |
Description: | Overall survival (OS) was defined as the time from the start of study treatment to death from any cause. OS was estimated using Kaplan-Meier estimate. |
Measure: | Objective Response Rate (ORR) by IRC and Investigator Assessment in BM-ve Population |
Time Frame: | From randomization to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 22.87 months) |
Safety Issue: | |
Description: | ORR was defined as the percentage of participants who had either a confirmed complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal. PR: >30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; and appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
Measure: | Time to Response by the Investigator Assessment in BM-ve Population |
Time Frame: | From randomization to the first recorded objective response (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 22.87 months) |
Safety Issue: | |
Description: | Time to response was defined as the time from randomization to the first recorded objective response (ie, CR or PR). CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal. PR: >30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
Measure: | Time to Response by the IRC Assessment in BM-ve Population |
Time Frame: | From randomization to the first recorded objective response (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 22.87 months) |
Safety Issue: | |
Description: | Time to response was defined as the time from randomization to the first recorded objective response (ie, CR or PR). CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal. PR: >30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
Measure: | Duration of Response (DOR) by IRC and Investigator Assessment in BM-ve Population |
Time Frame: | From the first date of documented response of CR or PR to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 22.87 months) |
Safety Issue: | |
Description: | DOR was defined as the number of days between the first date showing a documented response of CR or PR and the date of progression or death. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal. PR: >30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (+20%) in the sum of the target lesions or the appearance of new non-target lesions. |
Measure: | Time to Progression (TTP) by Investigator Assessment in BM-ve Population |
Time Frame: | From randomization until disease progression (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 22.87 months) |
Safety Issue: | |
Description: | Time to Progression (TTP) was defined as the time from the date of randomization to the date of the first evidence of disease progression as assessed using RECIST 1.1 criteria. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (+20%) in the sum of the target lesions or the appearance of new non-target lesions. |
Measure: | Time to Progression (TTP) by IRC Assessment in BM-ve Population |
Time Frame: | From randomization until disease progression (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 22.87 months) |
Safety Issue: | |
Description: | Time to Progression (TTP) was defined as the time from the date of randomization to the date of the first evidence of disease progression as assessed using RECIST 1.1 criteria. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (+20%) in the sum of the target lesions or the appearance of new non-target lesions. |
Measure: | Clinical Benefit Rate (CBR) by IRC and Investigator Assessment in BM-ve Population |
Time Frame: | From randomization to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 22.87 months) |
Safety Issue: | |
Description: | CBR was defined as the percentage of participants with either CR, PR, or stable disease (SD) with a duration of ≥6 months. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal. PR: >30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; and appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started; and Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. PD: > 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since treatment started or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
Measure: | Percentage of Participants Experiencing Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation of Study Drug |
Time Frame: | First dose date up to 30 days after the last dose of study drug (maximum up to 23.87 months) |
Safety Issue: | |
Description: | Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.03. An AE that met one or more of the following outcomes was classified as serious:
Fatal
Life-threatening
Disabling/incapacitating
Results in hospitalization or prolongs a hospital stay
A congenital abnormality
Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Immunomedics, Inc. |
Last Updated
April 30, 2021