8586 Background: IBI363 is a first-in-class, PD-1/IL-2 α-bias bispecific antibody fusion protein with great potential for immune-cold and immunotherapy (IO)-resistant tumors. Previously, IBI363 monotherapy demonstrated encouraging and durable efficacy in patients (pts) with IO-treated advanced NSCLC (2025 ASCO #8509). Here, we report a phase 1 study evaluating IBI363 plus platinum-based doublet-chemotherapy (PDC, pemetrexed/paclitaxel plus platinum) in 1L NSCLC. Methods: Previously untreated pts with advanced NSCLC, without sensitizing EGFR, ALK, or ROS1 alterations were enrolled. The safety lead-in evaluated IBI363 at 1.5 or 3 mg/kg Q3W plus PDC. In dose optimization (PD-L1 TPS < 50% required), pts were randomized 1:1:1 to 3 cohorts: 3-1.5 mg/kg (IBI363 3 mg/kg plus PDC in cycle 1, then 1.5 mg/kg Q3W plus PDC in subsequent cycles), 3 mg/kg (IBI363 3 mg/kg Q3W plus PDC) and 1.5 mg/kg (IBI363 1.5 mg/kg Q3W plus PDC). Stratification factors were squamous vs non-squamous, and PD-L1 TPS < 1% vs 1-49%. Primary endpoints were safety and efficacy assessed by investigators per RECIST v1.1. Secondary endpoints included pharmacokinetics (PK) and immunogenicity. Results: As of December 22, 2025, 80 pts were enrolled in safety lead-in (N = 11) and dose optimization (N = 69) with median follow-up (mFU) of 5.8 months (range: 0.9-9.5). Baseline characteristics (median age: 64 years, male: 88.8%, ECOG PS 1: 81.3%, stage IV: 72.5%, sqNSCLC: 66.3%) were balanced among 3-1.5 mg/kg (N = 23), 1.5 mg/kg (N = 28) and 3 mg/kg (N = 29) cohorts. Median treatment duration of IBI363 was 25.0 weeks (range: 4.0-41.1) while 65.0% pts with ongoing treatment, and 88.9% pts having completed ≥4 cycles of PDC. Grade≥3 (G3+) treatment-emergent adverse events (TEAEs) occurred in 81.3% pts including 65.2% for 3-1.5 mg/kg, 82.1% for 1.5 mg/kg and 93.1% for 3 mg/kg cohorts. Common TEAEs were anemia (any grades 78.8%, G3+ 18.8%), neutrophil count decrease (75.0%, G3+ 42.5%), white blood cell count decrease (63.8%, G3+ 20.0%), arthralgia (51.3%, G3+ 2.5%), and platelet count decrease (45.0%, G3+ 17.5%). IBI363-related AEs led to corresponding treatment discontinuation and death in 6.3% and 1.3% pts. In dose optimization, 65.2% pts had PD-L1 TPS < 1 and 34.8% had TPS 1-49%. Efficacy was evaluable in 62 pts with at least 1 tumor assessment. For 3-1.5 mg/kg cohort (N = 22), ORR was 86.4% (95% CI: 65.1-97.1, confirmed ORR cORR: 81.8%) and DCR was 100% (95% CI: 84.6-100). ORR was 85.7% for sqNSCLC (N = 14) and 87.5% for non-sqNSCLC (N = 8). For the 1.5 mg/kg (N = 19) and 3 mg/kg cohorts (N = 21), ORR was 57.9% (cORR: 42.1%) and 66.7% (cORR: 57.1%). PFS was immature (events 28.8%). Clinical PK data also supported an optimal benefit-risk profile based on efficacy and safety observed at 3-1.5 mg/kg. Conclusions: IBI363 plus PDC was well tolerated and showed encouraging efficacy in advanced NSCLC. Safety, efficacy, and PK data supported 3-1.5 mg/kg as the recommended dose. Clinical trial information: NCT06468098 .
Tu et al. (2026) studied this question.