NTX1088 (anti-PVR/CD155) + pembrolizumab drives 17% confirmed PRs in PD-(L)1–refractory solid tumors

NTX1088 is a first-in-class monoclonal antibody targeting PVR (CD155), intended to restore DNAM1 (CD226)-mediated T/NK-cell activity and counter multiple PVR-driven inhibitory axes (e.g., TIGIT/CD96). In the Phase 1a/1b open-label NTX-1088-01 dose-escalation/expansion trial (NCT05378425), 81 heavily pretreated patients with advanced PVR-expressing solid tumors received NTX1088 Q3W alone (12–1750mg; n=24) or with pembrolizumab 200mg Q3W (160–1750mg; n=57); median prior lines was 4 and prior CPI exposure was 70%, with no DLTs and 1750mg selected as the RDE. In the “active-dose” combo set (NTX1088 1200/1750mg + pembrolizumab), 35 response-evaluable patients had a confirmed ORR of 17% (6/35 PR; tumor types included gastric, bladder, NSCLC, HNSCC, melanoma), disease control of 63% (17% PR + 46% SD), and PR durability up to 20 months at cutoff (all but one PR ongoing); notably, all PRs occurred in prior CPI-exposed patients—where salvage rechallenge with single-agent PD-1 typically yields low single-digit/low-teens ORR in unselected populations, making 17% directionally interesting but still within the broad “IO-combo salvage” noise band without randomized benchmarks.