CTX-8371 PD-1×PD-L1 bispecific (CD80-CD28–enabling) shows 20% ORR post–checkpoint failure in Phase 1

CTX-8371 is a first-in-human PD-1×PD-L1 bispecific antibody designed to deliver dual checkpoint blockade while enabling CD80–CD28 engagement and promoting PD-1 cleavage from activated T cells. In a 3+3 Phase 1 dose-escalation trial (NCT06150664) in heavily pretreated, post-ICI metastatic melanoma/NSCLC/HNSCC/TNBC/HL (n=17; 15 imaging-evaluable; all with ≥2 prior lines), IV q2w dosing 0.1–10mg/kg produced an ORR of 20% (3/15: NSCLC irPR, TNBC PR, HL PR) and DCR of 60%, with longer/deeper responses emerging at ≥3mg/kg (ongoing TNBC responder with >90% tumor-volume reduction at 3mg/kg; ongoing HL metabolic PR at 10mg/kg). Safety was notably clean for a PD-(L)1-pathway agent in an ICI-refractory population—no DLTs, no MTD reached, and only one Grade 3 asymptomatic lipase increase (the only dose interruption); by contrast, common later-line benchmarks include docetaxel±ramucirumab in advanced NSCLC with ORR ~14%–23% and median PFS ~3.0–4.5 months, and sacituzumab govitecan in metastatic TNBC with ORR in the mid-30% range and median PFS ~5–6 months (albeit in different, larger Phase 3 settings).