Ascent 03 GS-US-592-6238
A randomized, open-label, phase 3 study of sacituzumab govitecan versus treatment of physician's choice in patients with previously untreated, locally advanced, inoperable or metastatic triple-negative breast cancer whose tumors do not express PD-L1 or in patients previously treated with anti-PD-(L)1 agents in the early setting whose tumors do express PD-L1
- Ages Eligible for Study : 18 years and older
- Sexes Eligible for Study: All
- Patients with locally advanced, inoperable, or metastatic TNBC who have not received previous systemic therapy for advanced disease and whose tumors are PD-L1 negative at screening. Alternatively, patients whose tumors are PD-L1 positive at screening will be eligible if they received an anti-programmed death (ligand) 1 (anti-PD-[L]1) inhibitor (ie, checkpoint inhibitor) in the adjuvant or neoadjuvant setting.
- a) Patients must have completed treatment for Stage I-III breast cancer, if indicated, and ≥ 6 months must have elapsed between completion of treatment with curative intent (eg, date of primary breast cancer surgery or date of last (neo)adjuvant chemotherapy administration [including anti-PD-(L)1 treatment], whichever occurred last) and first documented local or distant disease recurrence. Dates of postoperative radiotherapy are not included in this calculation.
- i) Patients who received taxane, gemcitabine, or platinum agents in the (neo)adjuvant setting can be treated with same class of chemotherapy (taxane or gemcitabine/carboplatin) if ≥ 12 months have elapsed between the completion of treatment with curative intent (eg, date of primary breast tumor surgery or date of last (neo)adjuvant chemotherapy administration, whichever occurred last) and first documented local or distant disease recurrence.
- ii) Patients enrolled should have received prior anthracycline in the (neo)adjuvant setting or be considered not eligible for anthracyclines as assessed by the treating physician.
- b) Patients presenting with de novo metastatic TNBC are eligible for this study.
- c) TNBC status and tumor PD-L1 CPS will be confirmed centrally on a recent or archival tumor specimen.
- Patients must have histologically or cytologically documented TNBC, according to current ASCO/CAP criteria, defined as negative for ER, progesterone receptor, and HER2. Patients initially diagnosed with hormone receptor-positive or HER2-positive breast cancer must have central confirmation of TNBC in a tumor biopsy obtained from a local recurrence or distant metastasis prior to entry. Tumor combined positive score (CPS) < 10 using the PD-L1 IHC 22C3 assay will be required for eligibility. Alternatively, patients with tumor CPS ≥ 10 will be eligible ifthey received an anti-PD-(L)1 inhibitor (ie, checkpoint inhibitor) in the adjuvant orneoadjuvant setting.
- Patients must have measurable disease by CT or MRI as per RECIST Version 1.1 criteria as evaluated locally. Tumor lesions situated in a previously irradiated area are considered measurable if unequivocal progression has been documented in such lesions since radiation.
- Have provided representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in blocks (preferred) or have at least 20 to 25 freshly sectioned unstained slides from fresh biopsy tissue (preferred) or archival tissue block for central testing of ER, progesterone receptor, HER2, and PD-L1 and additional biomarker testing.
- ECOG performance status score of 0 or 1 Demonstrates adequate organ function
Key Exclusion Criteria:
- Known or severe (≥ Grade 3) hypersensitivity or allergy to sacituzumab govitecan and/or the chemotherapy regimen of choice in the TPC arm (eg, nab-paclitaxel, paclitaxel, gemcitabine, or carboplatin), their metabolites, or formulation excipient
- Requirement for ongoing therapy with or prior use of any prohibited medications
- Patients may not have received systemic anticancer treatment within the previous 6 months or radiation therapy within 2 weeks prior to enrollment. Patients must have recovered (ie, > Grade 2 is considered not recovered) from AEs due to a previously administered agent at the time of study entry.
- Have previously received topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor.
- Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate (with the exception of those treated with chemotherapy) provided they have stable CNS disease (defined as radiographic stability demonstrated with a minimum of 2 posttreatment brain imaging assessments; one performed during screening) for at least 4 weeks prior to enrollment and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and have also been clinically stable for at least 2 weeks while taking ≤ 10 mg/day of prednisone or its equivalent. All patients with carcinomatous meningitis are excluded regardless of clinical stability.
- Myocardial infarction or unstable angina pectoris within 6 months of enrolment, History of serious ventricular arrhythmia, New York Heart Association Class III or greater congestive heart failure or known left ventricular ejection fraction of < 40%.
- Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or GI perforation within 6 months of enrollment.
The primary objective of this study is to compare the progression-free survival (PFS) between sacituzumab govitecan-hziy (SG) versus treatment of physician's choice (TPC) in participants with previously untreated, locally advanced, inoperable or metastatic triple-negative breast cancer whose tumors do not express programmed cell death ligand 1 (PD-L1) or in participants previously treated with anti-programmed cell death (ligand or protein) 1 (Anti-PD-(L)1) Agents in the early setting whose tumors do express PD-L1.