A phase II study of HB0025 (a PD-L1/VEGF bispecific antibody) in combination with chemotherapy as first-line treatment for non–small cell lung cancer (NSCLC).

8574 Background: HB0025, developed by Huaota, is a novel anti-PD-L1/VEGF bispecific antibody with VEGFR1D2 linked at the N-terminal of anti-PD-L1 antibody. This Phase II study assesses the efficacy and safety of HB0025 combined with chemotherapy in locally advanced unresectable, recurrent or metastatic non-small cell lung cancer (NSCLC). Methods: This open-label, multi-center, Phase II trial enrolled previously untreated patients with locally advanced unresectable, recurrent or metastatic NSCLC, without EGFR or ALK gene alterations. Participants were assigned to two cohorts: Cohort 1 (squamous NSCLC) received 20 mg/kg HB0025 plus carboplatin and paclitaxel every three weeks (Q3W) for 4-6 cycles, followed by HB0025 maintenance; Cohort 2 (non-squamous NSCLC) received 20 mg/kg HB0025 plus carboplatin and pemetrexed Q3W for 4-6 cycles, followed by maintenance with HB0025 and pemetrexed. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: As of January 5, 2026, 125 patients were enrolled in the study (62 patients in Cohort 1 and 63 patients in Cohort 2). The median age was 65 years old (range: 34, 74). The median follow-up period was 10.55 months (range: 1.0, 17.4). A total of 119 patients had at least one post-baseline tumor assessment. In Cohort 1, ORR was 84.5% (49/58), with subgroup ORRs of 81.3%, 72.2%, and 100% for PD-L1 TPS < 1%, 1–49%, and ≥50%, respectively; disease control rate (DCR) was 94.8% (55/58), median progression-free survival (mPFS) was 12.62 months, and median duration of response (mDOR) was immature. In Cohort 2, ORR was 65.6% (40/61), with ORRs uniformly 66.7% across all PD-L1 TPS subgroups; DCR was 96.7% (59/61), mPFS was 14.65 months, and mDOR was 12.06 months. Overall survival data remained immature. The most common immune-related adverse events (irAEs) were hypothyroidism (7.2%), hyperthyroidism (4.8%), increased alanine aminotransferase (4.0%), increased aspartate aminotransferase (3.2%), and increased blood thyroid stimulating hormone (3.2%). Anti-VEGF-related AEs of grade ≥3 were proteinuria (8.8%), hypertension (6.4%), hemorrhage (4.0%), and thromboembolism (4.0%). 6 (4.8%) patients discontinued HB0025 due to TRAE, and 2 (1.6%) patients died due to TRAE. Conclusions: The combination of HB0025 and chemotherapy has demonstrated promising efficacy and favorable safety as a first-line treatment for patients with locally advanced unresectable, recurrent or metastatic NSCLC. Multi-center, randomized, double-blind, controlled phase III trials in both squamous and non-squamous NSCLC have been initiated. Clinical trial information: NCT06758557 .