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.

person Sara M. Tolaney Dana-Farber Cancer Institute, Boston, MA info_outline Sara M. Tolaney, Angela DeMichele, Toshimi Takano, Hope S. Rugo, Charles Perou, Otto Metzger, Heather Anne Parsons, Cesar Augusto Santa-Maria, Gabrielle Betty Rocque, Wenliang Yao, Shawn W. Sun, Simonetta Mocci, Ann H. Partridge, Lisa A. Carey

Authors person Sara M. Tolaney Dana-Farber Cancer Institute, Boston, MA info_outline Sara M. Tolaney, Angela DeMichele, Toshimi Takano, Hope S. Rugo, Charles Perou, Otto Metzger, Heather Anne Parsons, Cesar Augusto Santa-Maria, Gabrielle Betty Rocque, Wenliang Yao, Shawn W. Sun, Simonetta Mocci, Ann H. Partridge, Lisa A. Carey Organizations Dana-Farber Cancer Institute, Boston, MA, University of Pennsylvania, Philadelphia, PA, The Cancer Institute Hospital of JFCR, Koto City, Tokyo, Japan, University of California Comprehensive Cancer Center, San Francisco, CA, University of North Carolina at Chapel Hill, Chapel Hill, NC, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, University of Alabama at Birmingham, Birmingham, AL, Gilead Sciences, Inc., Foster City, CA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Gilead Sciences, Inc 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/m 2 twice 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.

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