Multicenter phase 2 trial of HB0025 with chemotherapy for advanced squamous or nonsquamous non-small cell lung cancer

Bispecific antibodies targeting VEGF and PD-(L)1 pathways represent a promising therapeutic strategy for advanced non-small cell lung cancer (NSCLC). HB0025 is a novel bespecific antibody fusion targeting PD-L1 and VEGF. A phase 2 trial at 13 centers in China evaluated HB0025 plus chemotherapy in previously untreated, advanced NSCLC without sensitizing EGFR, ALK, or ROS1 alterations. Patients received intravenous 10-mg/kg HB0025 every 3 weeks or 20-mg/kg every 3 weeks plus chemotherapy: pemetrexed-carboplatin for nonsquamous and paclitaxel-carboplatin for squamous for up to 6 cycles, followed by HB0025 maintenance (with pemetrexed for nonsquamous) until disease progression or unacceptable toxic effects. Primary endpoints were safety and investigator-assessed objective response rate (ORR). Treatment efficacy was evaluable in 85 patients in the nonsquamous cohort and 84 patients in the squamous cohort. In the nonsquamous cohort, confirmed ORR was 34.6% with 10 mg/kg and 57.1 with 20 mg/kg. In the squamous cohort, ORR was 68.2% with 10 mg/kg and 74.2% with 20 mg/kg. Median PFS was 12.52 months in the nonsquamous cohort and 14.78 months in the squamous cohort, with 12-month PFS rates 54.3% and 62.1%, respectively, and 12-month OS rates of 75.8% and 85.5%, respectively. Grade 3 or higher treatment-related adverse events occurred in 65.9% in the nonsquamous cohort and 60.7% in the squamous cohort; with any-grade HB0025-related immune-related adverse events in 23.5% and 25%, respectively. The authors conclude that HB0025 plus chemotherapy showed promising antitumor activity and manageable safety in patients with advanced, driver variant-negative NSCLC in both nonsquamous and squamous histologic types, supporting further evaluation in randomized phase 3 trials.