First-in-class PD-1/IL-2 ^α-bias bispecific antibody IBI363 (TAK-928) in patients (pts) with advanced immunotherapy-resistant non–small cell lung cancer (NSCLC): Updated results from a phase I study.

Abstract

2618 Background: IBI363 is a first-in-class PD-1/IL-2 α-bias bispecific antibody fusion protein designed to block the PD-1/PD-L1 pathway and simultaneously activate the IL-2 pathway. IBI363 selectively expands and rejuvenates exhausted tumor-specific T cells by cis-activating IL-2 receptors. It has shown a manageable safety profile and encouraging efficacy in NSCLC (No. 8509, 2025 ASCO). The updated findings are reported here with a longer follow-up. Methods: Pts with advanced NSCLC who had progressed on standard therapy were enrolled and received IBI363 at dose levels of 0.002/0.01/0.3/0.6 mg/kg every week, 0.3/0.6/1 mg/kg Q2W or 1.5/2/3/4 mg/kg Q3W. Endpoints included safety, ORR, DCR, DOR and PFS assessed by investigator per RECIST v1.1, and OS. Results: As of Nov 20, 2025, 136 pts with NSCLC were enrolled (prior treatment lines ≥2 72.1%; including 67 with squamous NSCLC [sqNSCLC] and 66 with adenocarcinoma). The median follow-up was 14.4 months (mos, range 0.8─30.6). Both the ORR and DCR in sqNSCLC or adenocarcinoma were consistent with those reported previously. In pts with sqNSCLC at 1/1.5 mg/kg (n=28) and 3 mg/kg Q3W (n=31) (58/59 with prior IO therapy), median PFS was 5.5 (95% CI 1.5, 8.3) and 10.1 mos (6.0, 14.0), median OS was 12.5 (7.6, 22.2; maturity 71.4%) and 18.2 mos (10.7, not calculable [NC]; maturity 48.4%), with 24-month OS rate of 29.9% (14.2, 47.3) and 47.8% (28.7, 64.7), respectively. Among those who had a confirmed complete response (n=1) or partial response (PR, n=17), the overall DOR was 10.3 mos (7.0, 13.4; maturity 72.2%). In pts with EGFR wt adenocarcinoma at 0.6/1/1.5 mg/kg (n=30) and 3 mg/kg Q3W (n=25) (all with prior IO therapy), median PFS was 2.7 (1.4, 5.1) and 4.2 mos (3.0, 7.0), median OS was 17.5 (7.1, NC; maturity 56.7%) and 15.2 mos (9.6, NC; maturity 56.0%), with 24-month OS rate of 40.2% (22.2, 57.7) and 42.7% (23.1, 61.0), respectively; the overall DOR reached 21.3 mos (4.0, 21.3; maturity 40.0%) in those achieving a confirmed objective response (n=10, all PRs). Smoking is a major factor affecting treatment efficacy in adenocarcinoma. In smokers (n=31) and non-smokers with adenocarcinoma (n=24), the median OS was 23.4 (11.3, NC; maturity 48.4%) and 11.5 mos (5.6, 19.6; maturity 66.7%), respectively. In the overall population (n=136), treatment-emergent adverse events (TEAEs) occurred in 135 pts (99.3% any grades; 48.5% ≥G3). TEAEs led to treatment discontinuation in 11 (8.1%) pts. TEAEs led to death in 5 pts (3.7%) with only 1 event (0.7%) considered treatment-related (unexplained death). The most common TEAEs were arthralgia (52.2%; 3.7% ≥G3), anemia (46.3%; 4.4% ≥G3), and rash (39.0%; 8.8% ≥G3). Conclusions: IBI363 was well tolerated with a manageable safety profile consistent with earlier reports, and continued to show strong and durable efficacy in pts with heavily pretreated NSCLC. Clinical trial information: NCT05460767 .