HB0025 With Chemotherapy for Advanced Non-Small Cell Lung Cancer: A Phase 2 Nonrandomized Clinical Trial

To evaluate the efficacy and safety of HB0025 plus chemotherapy in previously untreated advanced, driver variant-negative NSCLC.

This open-label, multicenter, Phase 2 nonrandomized clinical trial enrolled patients with stage IIIB/C or IV NSCLC without sensitizing EGFR, ALK, or ROS1 alterations across 13 hospitals in China. Participants included those with nonsquamous NSCLC and squamous NSCLC.

Patients were enrolled from January 15, 2024, to May 21, 2025. Data cutoff was April 20, 2026.

The primary end points were safety and investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1. The secondary end points included disease control rate, duration of response, progression-free survival (PFS), and overall survival (OS).

Treatment efficacy was evaluable in 169 enrolled patients. The nonsquamous cohort included 85 patients (median [IQR] age, 63.0 [58.0-68.0] years; 26 [30.6%] female and 59 [69.4%] male patients), and the squamous cohort included 84 patients (median [IQR] age, 65.0 [60.0-69.0] years; 6 [7.1%] female and 78 [92.9%] male patients).

In the nonsquamous cohort, confirmed ORR was 36.4% (95% CI, 17.2%-59.3%) and 57.1% (95% CI, 44.1%-69.5%) in the 10-mg/kg and 20-mg/kg dose groups, respectively. In the squamous cohort, ORR reached 68.2% (95% CI, 45.1%-86.1%) and 74.2% (95%, 61.5%-84.5%) at the respective doses.

Median PFS was 12.52 months (95% CI, 10.15-16.56) in the nonsquamous cohort and 14.78 months (95% CI, 11.30 to not estimable) in the squamous cohort. The 12-month PFS rates were 54.3% (95% CI, 41.6%-65.3%) and 62.1% (95% CI, 49.9%-72.1%) in the nonsquamous and squamous cohorts, and the 12-month OS rates were 75.8% (95% CI, 65.0%-83.7%) and 85.5% (95% CI, 75.8%-91.5%), respectively.

Grade 3 or higher treatment-related adverse events occurred in 56 of 85 patients in the nonsquamous cohort and 51 of 84 (60.7%) in the squamous cohort, mainly as hematologic toxic effects. Any-grade immune-related adverse events related to HB0025 occurred in 20 patients (23.5%) in the nonsquamous cohort and 21 patients (25%) in the squamous cohort.

In this Phase 2 nonrandomized clinical trial, 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 clinical trials.