ASCENT-05/OptimICE-RD (AFT-65): Phase 3, randomized, open-label study of adjuvant sacituzumab govitecan (SG) + pembrolizumab (pembro) vs pembro ± capecitabine (cape) in patients (pts) with triple-negative breast cancer (TNBC) and residual disease after neoadjuvant therapy (NAT) and surgery.
Authors: Tolaney Sara M. , DeMichele Angela , Takano Toshimi , Rugo Hope S. , Perou Charles , Metzger Otto , Parsons Heather Anne , Santa-Maria Cesar Augusto , Rocque Gabrielle Betty , Yao Wenliang , Sun Shawn W. , Mocci Simonetta , Partridge Ann H. , Carey Lisa A. 
Published: June 2023

TPS619 Background: TNBC has an aggressive disease course with poor prognosis for pts with residual disease (RD) after NAT. In Ph 3 KEYNOTE-522, pts treated with polychemotherapy + the immune checkpoint inhibitor (ICI) pembro for ~1 year only had a 3-year event-free survival of 85% (Schmid P, et al. NEJM. 2022). SG is a Trop-2–directed antibody-drug conjugate approved for pretreated metastatic TNBC (mTNBC). In Ph 3 ASCENT, SG significantly improved both progression-free survival and overall survival (OS) compared with standard chemotherapy (CT) in pts with mTNBC who received ≥2 lines of therapy, with a manageable safety profile (Bardia A, et al. NEJM. 2021). Preclinical data suggest that SG also potentiates the activity of ICIs. The ASCENT-05 study will assess the value of adding SG to a pembro-based adjuvant therapy in pts with RD after NAT. Methods: ASCENT-05/OptimICE-RD (AFT-65, NCT05633654) is an open-label, global, multicenter, randomized, phase 3 study that evaluates efficacy and safety of SG + pembro versus pembro ± cape (per treating physician discretion) in pts with TNBC and RD in the post-NAT setting. Key eligibility criteria include pts ≥18 years with a history of cT1, cN1-2 or cT2-4, cN0-2 TNBC with RD in the breast or lymph node(s) after NAT and surgery. TNBC diagnosis per local assessment is based on estrogen receptor and progesterone receptor < 10%, and HER2-negative per ASCO/CAP. Other inclusion criteria are receipt of ≥6 cycles of neoadjuvant anthracycline- and/or taxane-based CT ± PD-(L)1 inhibitor ± radiotherapy postoperatively as clinically indicated, and adequate organ function with ECOG performance status 0-1. Key exclusion criteria include metastatic disease, prior ipsilateral/contralateral invasive breast cancer, prior treatment directed to another stimulatory/coinhibitory T-cell receptor, HER2-directed agents or TOPO-1 inhibitors, evidence of recurrent or distant metastatic disease after preoperative therapy and surgery, germline BRCA mutations, myocardial infarctions ≤6 months of enrollment or history of serious ventricular arrythmia or LVEF < 50%, and active serious infections requiring treatment. Pts will be randomized 1:1 to receive SG (10 mg/kg IV on d1 and d8, every 21d for 8 cycles) + pembro (200 mg IV on d1 every 21d for 8 cycles). Cape (1000 mg/m2twice daily, orally on d1-14, every 21d for 8 cycles) may be added to pembro in the control arm. The primary endpoint is invasive disease-free survival. Key secondary endpoints include OS, distant disease-free survival, incidence of treatment-emergent adverse events and clinical laboratory abnormalities, and time to worsening of quality of life based on FACT-B TOI scores. ASCENT-05 will enroll ~1500 pts and is currently open for recruitment. Clinical trial information: NCT05633654 .