Nogapendekin alfa inbakicept (NAI; IL-15R agonist) boosts PFS/OS signals when added to 1L PD-1–based SOC in metastatic NSCLC

Nogapendekin alfa inbakicept (NAI) is an IL-15 receptor agonist designed to expand NK cells and effector/memory T cells and sustain absolute lymphocyte counts (ALC), aiming to preserve “immune competence” during checkpoint inhibitor (CPI) therapy. In the ongoing randomized Phase 3 QUILT-2.023 (NCT03520686), an exploratory unblinding of 98 patients showed in Cohort A (PD-L1 TPS ≥1%; N=63) sustained ALC increases with CPI+NAI vs CPI alone (p=0.0065) and, in PD-L1 TPS ≥50% (N=45), median PFS 7.0 vs 2.2 months (HR 0.40; p=0.0298) with similar grade ≥3 CPI-related TEAEs (16% both arms)—noting this PFS is well below the usual pembrolizumab-monotherapy benchmark in TPS ≥50% disease (KEYNOTE-024 mPFS ~10.3 months), raising questions about comparability and maturity of this interim cut. In pooled platinum chemo-IO Cohorts B+C (ITT N=36; any PD-L1), ORR was 56% vs 33% and median OS 34.7 vs 20.2 months (HR 0.38; p=0.0394) with NAI vs control, while median PFS 18.9 vs 10.6 months did not meet significance (HR 0.48; p=0.1192)—for context, established 1L chemo-IO regimens typically deliver mOS ~17 months (KEYNOTE-407, squamous) and ~22 months (KEYNOTE-189, nonsquamous), with mPFS commonly in the ~6–9 month range depending on histology/regimen.