A phase 2 study of HLX07 plus serplulimab with or without chemotherapy versus serplulimab plus chemotherapy as first-line therapy in advanced squamous non-small cell lung cancer.

Abstract

8561 Background: Approved first-line therapies of PD-L1/PD-1 inhibitors plus chemotherapy conferred significant survival benefits for advanced squamous non-small cell lung cancer (sqNSCLC). However, the prognosis remains to be improved. The epidermal growth factor receptor (EGFR) is highly expressed in sqNSCLC and associated with a poor prognosis. This study aimed to compare the efficacy of HLX07, a novel humanized anti-EGFR antibody, plus serplulimab (anti-PD-1 antibody) ± chemo versus serplulimab plus chemo as first-line option for advanced sqNSCLC. Methods: This randomized, multicenter phase 2 study consisted of 4 parts that assessed varied combinations of HLX07 (at different doses), serplulimab, and chemotherapy. Part 3 evaluated the preliminary efficacy of the three-drug combination and is presented below. Patients with stage IIIB/IIIC or IV sqNSCLC that was not amenable to surgery or radiation therapy and high tumor expression of epidermal growth factor receptor (H score≥150) and no prior systemic therapy were randomized 1:1 to receive intravenous HLX07 at 800 mg (group A) or 1000 mg (group B), in combination with serplulimab (300 mg) and chemotherapy (carboplatin and nab-paclitaxel), once every three weeks. The primary endpoints were independent radiological review committee (IRRC)-assessed objective response rate (ORR) and progression-free survival (PFS) per RECIST 1.1. Results: As of 31 December 2024, 27 patients were enrolled and randomly assigned to group A (n=13) and group B (n=14) in part 3. 15 (55.6%) patients had metastatic disease. With a median follow-up of 16.0 months, IRRC-assessed confirmed ORR per RECIST 1.1 was 69.2% (95% CI 38.6–90.9) in group A and 71.4% (95% CI 41.9–91.6) in group B. Disease control rate was 92.3% (95% CI 64.0–99.8), and 100% (95% CI 76.8–100.0), respectively. Median PFS was 15.1 (95% CI 4.1–not available) months in group A and not reached in group B. The median overall survival and duration of response were not reached in either group as of the data cutoff date. All the patients in both groups reported treatment-emergent adverse events (TEAEs); most common TEAEs of any grade included neutrophil count decreased (92.3% vs. 71.4%), white blood cell count decreased (84.6% vs. 85.7%), anemia (84.6% vs. 78.6%), platelet count decreased (76.9% vs. 71.4%), hypokalemia (53.8% vs. 64.3%), rash (46.2% vs. 57.1%), alopecia and hypocalcemia (46.2% vs. 50.0% for each). 6 (46.2%) patients, and 8 (57.1%) in group A, and B reported immune-related adverse events, respectively. Conclusions: First-line HLX07 plus serplulimab and chemotherapy showed encouraging preliminary efficacy with a manageable safety profile in patients with advanced sqNSCLC which warrants further investigation. Clinical trial information: NCT04976647 .