ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer (ASCENT)

Brief Summary:
This is an international, multi-center, open-label, randomized, Phase III study in patients with metastatic TNBC refractory or relapsing after at least 2 prior chemotherapies (including a taxane) for their metastatic disease. Patients meeting eligibility will be randomized 1:1 to receive either sacituzumab govitecan or treatment of physician choice (TPC) Patients will be treated until progression, unacceptable toxicity, study withdrawal, or death, whichever comes first. Tumor progression leading to treatment withdrawal will be assessed by the investigator. Starting with the initial dose of sacituzumab govitecan or TPC, Imaging assessments will be obtained at least every 8 weeks until the occurrence of progression of disease requiring discontinuation of further treatment. All patients, will be followed every 4 weeks during the first year and every 8 weeks thereafter for survival follow-up

Detailed Description:
This is an international, multi-center, open-label, randomized, Phase III study in patients with metastatic TNBC refractory or relapsing after at least 2 prior chemotherapies (including a taxane) for their metastatic disease.

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 progression-free survival (PFS) in patients with metastatic TNBC previously treated with at least two systemic chemotherapy regimens.

The secondary objectives of the study are to compare between the two treatment groups for:
- Overall Survival (OS)
- Independently-determined Objective Response Rate (ORR), duration of response and time to onset of response per RECIST 1.1 criteria
- Quality of life
- Safety (adverse events, safety laboratories, incidence of dose delays and dose reductions, treatment discontinuations due to adverse events) Exploratory objectives include exposure-response analysis for the efficacy (PFS and OS) and safety (incidence of Grade 3-5 adverse events, related to UGT1A1 endpoints).

Four-Hundred and eighty-eight patients are anticipated to be enrolled. Approximately 150 institutions will participate in this study, including sites in North America and Europe.

Clinical sites will use standard ASCO/CAP criteria for the pathological diagnosis of TNBC, defined as negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Receptor results will be based on local assessment. TNBC status will be reviewed centrally but these results are not required prior to determining eligibility.

BRCA 1&2 mutational status will be collected, if known. Baseline serum biomarkers (CA15-3, CA27-29, and CEA) will be measured. A single whole-blood sample will be also collected from all patients for determination of UGT1A1 genotype for retrospective assessment predicting of toxicity.

The Sponsor will request slides from prior (archived) biopsy or surgical specimens, particularly for immunohistology documentation of tumor Trop-2 expression and other appropriate tumor markers, including topoisomerase 1.

Patients meeting eligibility will be randomized 1:1 to receive either sacituzumab govitecan or treatment of physician choice (TPC), which needs to be selected prior to randomization from one of the 4 allowed regimens. Randomization will be stratified by number of prior chemotherapies for advanced disease (2-3 vs > 3) and geographical location (North America vs Europe).

Patients will be treated until progression, unacceptable toxicity, study withdrawal, or death, whichever comes first. Tumor progression leading to treatment withdrawal will be assessed by the investigator.

No crossover to sacituzumab govitecan treatment will be allowed after discontinuing treatment in the TPC arm, but otherwise there is no restriction on subsequent therapies that a patient may receive after discontinuing the study.

All patients, including those prematurely terminating study participation, will be followed every 4 weeks for survival follow-up.


Study Type: Interventional  (Clinical Trial)
Estimated Enrollment: 488 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III Study of Sacituzumab Govitecan (IMMU-132) in Refractory/Relapsed Triple-Negative Breast Cancer
Actual Study Start Date: October 12, 2017
Estimated Primary Completion Date: December 2019
Estimated Study Completion Date: June 2020

Arms:
- Experimental: IMMU-132
- Active Comparator: Control Arm