ASPRIA: A single-arm phase 2 trial of atezolizumab with sacituzumab govitecan to prevent recurrence in triple-negative breast cancer.

Abstract

TPS644 Background: Despite marked improvements in neoadjuvant chemoimmunotherapy (NACT) and adjuvant treatment for patients with early-stage triple negative breast cancer (TNBC), over 30% of patients with residual disease after NACT experience disease recurrence or death within 36 months. Understanding which patients are at greatest risk of relapse and designing effective interventions to prevent disease recurrence are major unmet needs. Circulating tumor DNA (ctDNA) can detect molecular residual disease (MRD) in TNBC and has demonstrated prognostic and predictive ability in the neoadjuvant setting; ctDNA thus represents a promising biomarker to select at-risk patients. Sacituzumab govitecan is a Trop-2 targeted antibody-drug conjugate leveraging a topoisomerase 1 payload that is approved for metastatic HR+ breast cancer and TNBC. Atezolizumab is an immune checkpoint inhibitor that interferes with the binding of PD-L1 to PD-1. The ASPRIA trial hypothesizes that ctDNA can identify patients with TNBC and residual disease after NACT at greatest risk for relapse, and that the combination of sacituzumab govitecan and atezolizumab may effectively treat MRD through cytotoxicity and anti-tumor immunity, leading to ctDNA clearance and improved clinical outcomes. Methods: The ASPRIA trial is an open-label, single-arm phase II trial evaluating sacituzumab govitecan in combination with atezolizumab in patients with early-stage TNBC. Eligible patients have residual invasive disease in the breast and/or lymph nodes following curative-intent therapy and detectable ctDNA, as assessed by a personalized, tumor-informed assay (Signatera, Natera, Inc.). The study includes a screening phase, with ctDNA presence assessed for the first 60 individuals to ensure feasibility, with a minimum prevalence threshold of approximately 15%. Patients with detectable ctDNA will undergo restaging imaging, and those without evidence of metastatic disease proceed to treatment. Up to 32 ctDNA-positive patients will receive atezolizumab 1200 mg IV on day 1 plus sacituzumab govitecan 10 mg/kg IV on days 1 and 8 of a 21-day cycle for 6 cycles. On-treatment ctDNA assessments will occur at weeks 3, 9, and at end of therapy. Participants will be followed for recurrence and survival every 6 months for 3 years. The primary objective is to determine the rate of ctDNA clearance after 6 cycles of therapy. Secondary objectives include estimating the ctDNA prevalence, assessing clearance after 1 and 3 cycles, evaluating recurrence risk and survival outcomes (iDFS, RFI, DMFS), and characterizing safety (per CTCAE v5). Correlative studies will examine predictors of ctDNA positivity, associations between treatment response and Trop-2 or PD-L1 expression in primary and residual tumors, temporal ctDNA dynamics in relation to relapse, and patient perspectives on ctDNA testing. Clinical trial information: NCT04434040 .