Anti-CD73 Oleclumab Fails but ctDNA Wins in First-Line mTNBC

In the randomized Phase I/II SYNERGY trial (NCT03616886), 133 untreated patients with locally advanced or metastatic triple-negative breast cancer (TNBC) received weekly carboplatin (a platinum-based chemotherapy) and paclitaxel (a taxane) plus durvalumab (a PD-L1 inhibitor), either with oleclumab (an anti-CD73 monoclonal antibody; arm A, n = 69) or without it (arm B, n = 64). The mOS was similar between the arms—25.1 vs. 20.9 months (HR 0.97, p = 0.90)—and PFS actually trended shorter with oleclumab (4.8 vs. 5.4 months; HR 1.22). Circulating tumor DNA (ctDNA) positivity decreased from 77% at baseline to 18% by week 13 and consistently correlated with poorer PFS and overall survival. Notably, all 12 “exceptional” long-term responders achieved ctDNA clearance.