HLX07, a novel anti-EGFR antibody, for locally advanced and metastatic cutaneous squamous cell carcinoma: an open-label, multicenter, phase II trial

Background: Cutaneous squamous cell carcinoma (CSCC) accounts for 20% of all cutaneous cancers. Systemic treatment options for advanced CSCC (aCSCC) include immunotherapy, chemotherapy, and epidermal growth factor receptor (EGFR)-targeted therapy, although their efficacy is limited. HLX07 is a novel anti-EGFR antibody that showed preliminary anti-cancer activity and tolerability in phase I studies. Objectives: To evaluate the efficacy and safety of HLX07 in patients with aCSCC. Design: This is a multicenter, open-label, two-part phase II study. In Part 1, patients with metastatic or locally aCSCC not amenable to surgery or curative radiotherapy received 1500 mg (group A) or 1000 mg (group B) HLX07 intravenously every 3 weeks. In Part 2, patients received HLX07 at dose level determined with Part 1 results. Methods: The primary endpoint was objective response rate (ORR) assessed by an independent radiology review committee (IRRC). Secondary endpoints included other efficacy endpoints, safety, pharmacokinetics, immunogenicity, and quality of life. Results: Here we focus on Part 1 data. As of April 30, 2024, 31 patients were enrolled (group A, 21; group B, 10). Most patients had metastatic disease (85.7%; 90.0%). Per IRRC assessments, ORR was 19.0% (95% confidence interval (CI), 5.5–41.9) for group A and 60.0% (26.2–87.8) for group B; median progression-free survival was 4.9 (95% CI, 1.4–6.5) and 7.9 (95% CI, 2.2–11.1) months, and median duration of response was 5.0 (95% CI, 2.9–not evaluable (NE)) and 7.4 (95% CI, 2.8–NE) months, respectively. Median overall survival was 11.8 months (95% CI, 5.9–NE) and not reached (95% CI, 2.2–NE). Grade ⩾3 treatment-related adverse events (TRAEs) occurred in 8 (38.1%) and 3 (30.0%) patients, respectively. No TRAE leading to death or treatment discontinuation was reported. Conclusion: HLX07 monotherapy has demonstrated promising efficacy and a favorable safety profile in treating aCSCC, warranting further investigation in large-scale clinical studies. Trial registration: ClinicalTrials.gov NCT05238363.