IPH5201 (anti-CD39) + durvalumab (PD-L1) + platinum chemo posts 27.5% pCR in resectable NSCLC—signal enriches to 50% in PD-L1≥50%

IPH5201 is a blocking anti-CD39 monoclonal antibody (reduces adenosine generation by inhibiting CD39-mediated ATP breakdown) combined with durvalumab (anti–PD-L1) on top of neoadjuvant platinum-based chemotherapy in the single-arm Phase 2 MATISSE trial (NCT05742607) for previously untreated, resectable stage II–IIIA NSCLC (n=40; data cutoff Feb 11, 2025). Planned surgery proceeded in 87.5% (35/40); overall pCR was 27.5% (11/40; 95%CI 14.6–43.9), with higher pCR in PD-L1≥1% (35.7%, n=28) and PD-L1≥50% (50%, n=14) subgroups—numerically above perioperative durvalumab+chemo benchmarks from AEGEAN (pCR 17.2% overall; exploratory subgroup pCR figures reported as 21.2% for PD-L1≥1% and 27.5% for PD-L1≥50% in the abstract’s cross-trial comparison). Safety looked similar to durvalumab+chemo: 89.5% had treatment-related AEs, mostly grade 1–2, and no new safety signals were flagged; pharmacodynamics showed complete/sustained soluble and membrane CD39 saturation in blood, and tumor CD39+ (and CD8+) cell density trended higher at baseline among pCR/mPR responders.