Results from Phase 2 Study of Pimurutamab (HLX07) in Advanced Cutaneous Squamous Cell Carcinoma Published in Therapeutic Advances in Medical Oncology

Recently, results from part 1 of a Phase 2 study of pimurutamab (HLX07), a novel anti-EGFR monoclonal antibody independently developed by Henlius, in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) were published in the international oncology journal Therapeutic Advances in Medical Oncology. HLX07 monotherapy has demonstrated promising efficacy and a favorable safety profile in treating advanced CSCC (aCSCC), warranting further investigation in larger populations. ORR Reached 60.0%, Demonstrating Promising Antitumour Activity CSCC is one of the most common forms of skin cancer, accounting for approximately 20% of all cutaneous malignancies, with its incidence continuing to rise globally.¹˒² While patients with early-stage disease generally have a favorable prognosis following surgery or radiotherapy, outcomes remain poor for patients with locally advanced or metastatic disease who are not candidates for these treatments, with 10-year survival rates below 20%.¹˒³ Current systemic treatment options for aCSCC include immunotherapy, chemotherapy and epidermal growth factor receptor (EGFR) antibodies.¹˒⁴˒⁵ Although immunotherapy has become an important treatment option, a substantial proportion of patients do not respond. Evidence supporting chemotherapy remains limited, and no systemic chemotherapy has been approved specifically for advanced CSCC. Given the frequent expression of EGFR and the low rate of RAS mutations in CSCC, EGFR represents a potentially relevant therapeutic target.⁶˒⁷ However, the efficacy of existing anti-EGFR antibodies remains limited, more efficacious and tolerable anti-EGFR antibodies represent an attractive direction for further drug development. HLX07 is a novel, fully-humanised anti-EGFR monoclonal antibody. Previous preclinical and early-stage clinical studies have demonstrated encouraging antitumour activity and safety, while its pharmacokinetic profile supports once-every-three-weeks (Q3W) administration. These newly published Phase 2 study further evaluated the efficacy and safety of HLX07 monotherapy in patients with locally advanced or metastatic CSCC. This was an open-label, multicenter, two-part phase 2 clinical trial evaluating the efficacy and safety of HLX07 monotherapy in patients with aCSCC. The results from Part 1 were reported. The study enrolled patients with aCSCC with lymph node or distant metastases, as well as those with locally aCSCC who were not candidates for surgery or curative radiotherapy. As of April 30, 2024, a total of 31 patients were enrolled, most of whom had metastatic CSCC, including 21 patients in the 1500 mg group (Group A) and 10 in the 1000 mg group (Group B). In Group B, 60.0% of patients had received prior systemic anticancer treatment. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR), time to response, safety, pharmacokinetics, immunogenicity and quality of life. The study also explored potential associations between treatment efficacy and tumour expression levels of EGFR and PD-L1. Long-term follow-up showed encouraging antitumour activity and durable clinical benefit. Based on BICR assessments, the confirmed ORR was 19.0% in Group A, with all objective responses being partial responses (PRs). In Group B, the confirmed ORR reached 60.0%, including one complete response (CR). The DCR was 61.9% and 100%, respectively. The median PFS was 4.9 months in Group A and 7.9 months in Group B, while the median DOR was 5.0 months and 7.4 months, respectively. The median OS was 11.8 months in Group A and not reached in Group B at data cutoff. Manageable Safety Profile Supports Further Dose Evaluation HLX07 monotherapy demonstrated a manageable safety profile, with no new safety signals identified. These findings supported 1000 mg as the dose for further clinical evaluation of HLX07. Future studies will further evaluate its clinical benefit in patients with advanced CSCC and explore the potential association between EGFR protein expression and treatment benefit. Addressing Unmet Needs Across EGFR-Driven Tumours Epidermal growth factor receptor (EGFR) is widely overexpressed across multiple solid tumours, including both squamous and non-squamous non-small cell lung cancer (NSCLC), and is considered a key driver of tumour initiation, progression, and treatment resistance.8 Notably, EGFR overexpression is distinct from EGFR sensitizing mutations, with relatively low correlation between the two.9 In particular, classical sensitizing EGFR mutations are rare among patients with squamous NSCLC.10 As a result, the majority of patients with EGFR-overexpressing squamous tumours do not harbour sensitizing EGFR mutations and are therefore unlikely to benefit from EGFR tyrosine kinase inhibitors (TKIs).10 In recent years, anti-EGFR monoclonal antibodies in combination with chemotherapy have demonstrated clinical benefit in diseases such as squamous NSCLC.11,12 Meanwhile, PD-1/PD-L1 inhibitor-based immunotherapy combined with chemotherapy has significantly improved first-line outcomes for patients with advanced squamous NSCLC. Nevertheless, there remains room for further improvement, highlighting the continued need for new combination treatment strategies.13-23 From monotherapy to combinations with immunotherapy, chemotherapy and antibody-drug conjugates (ADCs), HLX07 is being evaluated through a range of treatment strategies to further explore its therapeutic potential in EGFR-high solid tumours. A phase 2/3 clinical study of HLX07 in combination with Henlius’ anti-PD-1 monoclonal antibody serplulimab (trade name in Europe: Hetronifly®) and chemotherapy as first-line treatment for patients with advanced sqNSCLC has dosed its first patient in China, with a Clinical Trial Notification (CTN) also completed in Australia. In addition, a Phase 1b/2 clinical study evaluating HLX07 in combination with HLX43, Henlius' self-developed novel PD-L1-targeting antibody-drug conjugate (ADC), in patients with advanced/metastatic solid tumours has been approved by China's National Medical Products Administration (NMPA). Moving ahead, Henlius will remain committed to its patient-centric approach, with a continued focus on addressing unmet medical needs and strengthening the differentiated development of its innovative assets, with the aim of bringing quality and affordable treatments to more patients with cancer. References 1. Wysong A. Squamous-cell carcinoma of the skin. N Engl J Med 2023; 388(24): 2262–2273. 2. Guo A, Liu X, Li H, et al. The global, regional, national burden of cutaneous squamous cell carcinoma (1990–2019) and predictions to 2035. Eur J Cancer Care 2023; 2023(1): 5484597. 3. Jiang R, Fritz M and Que SKT. Cutaneous squamous cell carcinoma: an updated review. Cancers (Basel) 2024; 16(10): 1800. 4. National Comprehensive Cancer Network. Squamous cell skin cancer, NCCN guidelines version 1.2024. NCCN Clinical Practice Guidelines in Oncology, 2024. 5. Stratigos AJ, Garbe C, Dessinioti C, et al. 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