Recently, results from five clinical trials of Henlius' self-developed products, including novel anti-PD-1 mAb HANSIZHUANG (serplulimab), anti-EGFR mAb HLX07 and daratumumab biosimilar candidate HLX15, were released at European Society for Medical Oncology Asia (ESMO Asia) Congress 2024. The above studies involve ASTRUM-004R led by Professor Bo Shen from Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital, Nanjing Medical University, a phase 2 study exploring fruquintinib combined with serplulimab as 1st line treatment in advanced non-clear cell renal cell carcinoma (nccRCC) initiated and led by Professor Jiwei Huang from Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, HLX07-NPC201 led by Professor Li Zhang from Sun Yat-sen University Cancer Center, HLX07-CSCC201 led by Professor Changxing Li from Nanfang Hospital of Southern Medical University, and HLX15-001 led by Professor Yu-wen Su from Sir Run Run Hospital, Nanjing Medical University.
Among them, the study results of Phase 2 Clinical Trial in nccRCC was selected as Mini Oral. And the study results of HLX07-NPC201 were accepted as a Late-breaking Abstract and were presented by Professor Li Zhang. Moreover, the results of HLX07-CSCC201 were first presented at ESMO Asia 2023, where its poster won the best poster award, and were presented with updated results at ESMO Asia 2024.
HANSIZHUANG (Serplulimab)
HANSIZHUANG (serplulimab) is a recombinant humanised anti-PD-1 monoclonal antibody（mAb）injection independently developed by Henlius, and the world's first anti-PD-1 mAb approved for the first-line treatment of SCLC. It has been approved in China and multiple countries in Southeastern Asia. Underpinned by the patient-centric strategy, Henlius has carried out a differentiated and multi-dimensional layout in the field of gastrointestinal cancer and lung cancer, covering a wide variety of indications. Up to date, HANSIZHUANG has been approved by the National Medical Products Administration (NMPA) for the treatment of 5 indications, benefiting around 90,000 patients. Moreover, a wide variety of clinical trials on immuno-oncology combination therapies in differentiated indications has been initiated by the company to further explore the efficacy of the product, such as HANSIZHUANG plus bevacizumab and chemotherapy as first-line treatment for patients with metastatic colorectal cancer (mCRC), HANSIZHUANG plus chemotherapy as neoadjuvant/adjuvant therapy for gastric cancer (GC), and HANSIZHUANG plus chemotherapy and concurrent radiotherapy in patients with limited-stage small cell lung cancer (LS-SCLC), etc.
ASTRUM-004R
Title
First-Line Serplulimab for Advanced Squamous Non-Small Cell Lung Cancer: A Multicenter, Single-Arm, Real-World ASTRUM-004R Study
Study design
ASTRUM-004R is a real-world study conducted by Jiangsu Cancer Hospital and 13 other sites in China. Unlike the strict eligibility criteria of the ASTRUM-004 trial, this study accepts more flexible baseline characteristics and chemotherapy choices. The primary endpoints are objective response rate (ORR) and real-world progression-free survival (rwPFS).
Results
A total of 100 patients were eligible for analysis. Among these, 70 patients elected to receive either paclitaxel (n=34) or nab-paclitaxel (n=36) plus platinum and serplulimab as the immunochemotherapy regimen. The median age was 68.0 years, predominantly males (93.0%) and smokers (70.0%). The majority had an ECOG performance status of 0 or 1 (80.0%), and 37% presented with comorbidities. Additionally, 42.0% of patients received induction therapy for >4 cycles, and 11.0% had undergone radiotherapy. The ORR was 64.0% (95% CI 53.8-73.4), and the DCR was 96.0% (95% CI 90.1-98.9). Although numerically higher ORR was observed in patients treated with nab-paclitaxel (75.0%) compared to paclitaxel (55.9%), this difference was not statistically significant. Moreover, both treatments showed comparable DCRs (100% for paclitaxel vs. 97.2% for nab-paclitaxel). At the time of data cutoff (July 2024), median rwPFS and OS had not been reached, with the 1-year rwPFS rate estimated by the Kaplan-Meier method being 51.6% (95% CI 33.9-78.5). Adverse events of special interest (AESI) were reported in 17.0% of patients.
Conclusion
The results confirmed the efficacy and well-tolerance of serplulimab in squamous NSCLC. In addition, the choice of chemotherapy agents, whether paclitaxel plus platinum, nab-paclitaxel plus platinum, or other combinations, has shown consistent efficacy. These findings support the broader application of serplulimab-based chemotherapy as a first-line treatment.
A Phase 2 Clinical Trial in nccRCC
Title
Efficacy and safety of fruquintinib combined with serplulimab as 1st line treatment in advanced non-clear cell renal cell carcinoma (nccRCC): A single-arm, multicentre clinical trial
Study design
This is a single-arm, multi-center, prospective Phase 2 clinical study, aiming to compare the efficacy and safety of the first-line treatment of non-clear cell renal cell carcinoma (nccRCC) with serplulimab combined with fruquintinib. The trial is mainly divided into safety run-in phase and dose expansion phase, with a total of 39 patients enrolled. In the safety safety run-in phase, 6 patients are planned to be enrolled; in the dose expansion phase, 33 patients are planned to be enrolled. All of enrolled patients will receive serplulimab (4.5 mg/kg, IV, Q3W) combined with fruquintinib (5 mg, QD, PO, 2 weeks on/1 week off) until disease progression or intolerable toxicity. The primary endpoint is PFS; the secondary endpoints include ORR， DCR, and safety.
Results
As of September 30, 2024, 16 patients have been enrolled, with a median follow-up time of 8.6 months. The median PFS has not been reached. The 6-month PFS rate is 77.1%. 8 patients have achieved partial response (PR), with an ORR of 50.0%, and the DCR is 87.5%. No dose-limiting toxicity was observed.
Conclusion
In patients with advanced nccRCC, the combination of serplulimab and fruquintinib has significant efficacy and tolerability.
HLX07
HLX07 is an innovative drug targeting EGFR independently developed by Henlius. Adopting the self-developed advanced antibody engineering platform, Henlius re-engineered cetuximab by humanising its Fab regions and minimizing its glycan contents to generate HLX07 to reduce immunogenicity and maintain a high binding affinity of the product. Currently, Henlius is conducting phase 2 clinical trials to explore HLX07 as monotherapy or in combination with HANSIZHUANG (serplulimab) for the treatment of solid tumours including esophageal squamous cell carcinoma (ESCC), cutaneous squamous cell carcinoma (CSCC), and nasopharyngeal carcinoma (NPC).
HLX07-NPC201
Title
First-line HLX07 vs. Placebo Combined with Serplulimab and Chemotherapy for Nasopharyngeal Cancer: a Randomised, Double-blind, Multicentre Phase 2 study
Study design
This is a randomised, double-blind, multicentre phase 2 study. Patients with pathohistologically confirmed, unresectable, recurrent or metastatic NPC that is not amenable to local or radical treatment and had no prior systemic therapy are randomized 2:1 to receive intravenous HLX07 (1000 mg) or placebo once every 3 weeks (Q3W). Serplulimab (300 mg), and chemotherapy (gemcitabine and cisplatin) were also given Q3W for up to 2 years, and 6 cycles, respectively. The primary endpoint is independent radiological review committee (IRRC)-assessed objective response rate (ORR) per the RECIST version 1.1. Secondary endpoints include other efficacy endpoints, safety, pharmacokinetics and biomarker explorations.
Results
By the data cutoff date of September 06, 2024, 75 patients were randomised to receive HLX07 (n=50) or placebo (n=25), combined with serplulimab and chemotherapy. Median follow-up duration was 10.8 months. A trend of a progression-free survival (PFS) benefit was observed for the HLX07 group compared to the placebo group (IRRC-assessed median PFS: not reached [NR] vs. NR; stratified HR 0.74, 95% CI 0.33-1.66). The 12-month PFS rate was 63.0% and 52.8% for the respective groups. IRRC-assessed confirmed ORR was 72.0% for the two groups. A trend of an improved median duration of response was also observed for the HLX07 group (median: NR vs. NR; stratified HR 0.56, 95% CI 0.22-1.43). Serious treatment-related adverse events occurred in 14 (28.0%) patients in the HLX07 group, and 8 (32.0%) in the placebo group.
Conclusion
The addition of HLX07 to serplulimab and chemotherapy showed preliminary efficacy along with a manageable safety profile. This treatment regimen warrants further investigation as a potential first-line option for R/M-NPC patients.
HLX07-CSCC201
Title
Efficacy and Safety of HLX07 Monotherapy in Advanced Cutaneous Squamous Cell Carcinoma: an Open-label, Multicentre Phase 2 Study
Study design
This study consisted of 2 parts. Part 1 explored the preliminary efficacy and was presented below; part 2 evaluated the efficacy and safety of HLX07 (at a fixed dose based on part 1) in a larger cohort, Patients with advanced CSCC harbouring lymph node or distant metastasis, or locally advanced CSCC that was not amenable to surgery/radical radiation therapy received intravenous HLX07 at 1500 mg (group A) or 1000 mg (group B) once every 3 weeks in part 1. The primary endpoint was independent radiological review committee (IRRC)-assessed ORR per RECIST 1.1. Secondary endpoints included other efficacy measures, safety, pharmacokinetics, immunogenicity, and quality of life assessments.
Results
By the data cutoff date of April 30, 2024, the median follow-up duration was 19.1 months and 12.7 months in group A (n=21), and B (n= 10), respectively. IRRC-assessed confirmed ORR was 19.0% (95% CI 5.5-41.9) in group A and 60.0% (95% CI 26.2-87.8) in group B. IRRC -assessed median progression-free survival was 4.9 months (95% CI 1.4-6.5) in group A and 7.9 months (95% CI 2.2-11.1) in group B. Median OS was 11.8 months (95% CI 5.9-NE) in group A and not reached in group B, with a 12-month OS rate of 45.7% and 56.0% for the respective groups. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 8 (38.1%), and 3 (30.0%) patients in group A and B, respectively. No TRAE leading to treatment discontinuation or death was reported.
Conclusion
With an additional 8.9 months of follow-up, HLX07 monotherapy at 1000 mg continued to demonstrate encouraging antitumour efficacy alone with manageable safety in Chinese patients with advanced CSCC.
HLX15
HLX15 is a fully human anti-CD38 IgG1κ monoclonal antibody independently developed by Henlius. The indication to be developed for HLX15 is multiple myeloma (MM). In accordance with the biosimilar guidelines of NMPA, EMA, and FDA, HLX15 has been developed strictly following the principles of stepwise development, comparability and similarity assessment and has been compared head-to-head with reference daratumumab via analytical studies and preclinical studies. In June 2024, the phase 1 clinical trial of HLX15 met its primary endpoint.
HLX15-001
Title
A Randomised, Double-blind, Phase 1 Study to Compare the Pharmacokinetics, Safety, Tolerability, and Immunogenicity of HLX15 and Daratumumab in Healthy Male Participants
Study design
This phase 1 study consisted of 2 parts. Part I was a single-centre, open-label, randomised, pilot study. Part II was a multicentre, randomised, double-blind, pivotal study to compare HLX15 with daratumumab and is presented below. Healthy Chinese male participants aged 18–60 years were enrolled and randomised 1:1:1:1 to receive a single intravenous infusion of HLX15 (group A), China-sourced daratumumab (group B), US-sourced daratumumab (group C), or European Union-sourced daratumumab (group D) at 8 mg/kg. Primary endpoint was the area under the serum concentration-time curve from time 0 to infinity (AUC0-inf). Secondary endpoints included other pharmacokinetic (PK) parameters, safety, and immunogenicity.
Results
Of the 172 participants enrolled in part II (43 per group), 165 (group A, n=41; group B, n=41; group C, n=42; group D, n=41) were included in the PK analysis. The geometric mean ratio and its 90% confidence intervals for primary endpoint AUC0-inf between any two groups were within the predefined equivalence margin of 80.00–125.00%, indicating PK similarity between HLX15 and the reference daratumumab. Other PK parameters were also comparable. Treatment-emergent adverse events (AEs), treatment-related AEs and AEs of special interest were mostly mild (grade 1 to 2) and similar across all groups. The overall positive rate of anti-drug antibody was also comparable across the groups with no neutralizing antibody being detected.
Conclusion
PK similarity between HLX15 and daratumumab from different regions was demonstrated, along with comparable safety and immunogenicity profiles. HLX15 is a promising biosimilar of daratumumab that warrants further investigation.