Recently, results from four phase 1/2 clinical trials conducted in patients with advanced solid tumours of Henlius' self-developed novel products, including anti-PD-1 mAb HANSIZHUANG (serplulimab), anti-EGFR mAb HLX07 and anti-LAG-3 mAb HLX26, were released as poster presentations at European Society for Medical Oncology Asia (ESMO Asia) Congress 2023. The above studies involves HLX10-008-HCC201 led by Professor Jia Fan from Zhongshan Hospital of Fudan University, HLX10HLX07-sqNSCLC-201 led by Professor Yi-Long Wu from Guangdong Provincial People's Hospital, HLX07-CSCC201 led by Professor Changxing Li from Nanfang Hospital of Southern Medical University, and HLX26-002 led by Professor Yanmin Wu from Xuzhou Central Hospital. Among them, the poster of HLX07-CSCC201 won the best poster award at ESMO Asia Congress 2023.

 HANSIZHUANG (Serplulimab)

HANSIZHUANG (generic name: serplulimab injection) is an innovative anti-PD-1 monoclonal antibody independently developed by Henlius and become the first anti-PD-1 mAb for the first-line treatment of SCLC. Since its first launched in March 2022, HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC) and esophageal squamous cell carcinoma (ESCC). Moreover, its marketing application of the first-line treatment for ES-SCLC is under review by the EMA, with approval expected in the first half of 2024. Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. It has successively obtained clinical trial approvals in China, the U.S., the EU and other countries and regions to initiate more than 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications. 

HLX10-008-HCC201

Title

A phase 2 study of serplulimab (a programmed death-1 inhibitor) with or without HLX04 (a bevacizumab biosimilar) for the treatment of advanced hepatocellular carcinoma

Study design

Patients with advanced HCC who failed prior systemic therapy received serplulimab 3 mg/kg plus HLX04 5 mg/kg (group A), serplulimab 3 mg/kg plus HLX04 10 mg/kg (group B), or serplulimab 3 mg/kg monotherapy (group C). Patients with previously untreated advanced HCC were enrolled in group D and given serplulimab 3 mg/kg plus HLX04 10 mg/kg. All treatments were administered intravenously every 2 weeks. The primary endpoint was safety.

Results

This open-label, multicentre phase 2 study was conducted in China; 28 hospitals enrolled patients. Results of group A and B have been previously published; here we present results of group C and D. As of 7 February 2023, 21 and 61 patients were enrolled in group C and D. The median follow-up duration was 26.0 and 25.5months, respectively. 10 (47.6%) patients in group C and 29 (47.5%) in group D reported grade ≥3 treatment-emergent adverse events. 1 (4.8%) patient in group C died from treatment-related hepatic failure; 1 (1.6%) in group D died from treatment-related hepatic failure and disease progression. As assessed by an independent radiological review committee (IRRC) per RECIST v1.1, the objective response rate was 4.8% (95% confidence interval [CI] 0.1–23.8) in group C and 27.9% (95% CI 17.1–40.8) in group D. IRRC-assessed median progression-free survival was 1.8 months (95% CI 1.4–2.8) and 7.3 months (95% CI 2.8–11.0) in group C and D, respectively. Median overall survival was 16.0 months (95% CI 3.6–not evaluable [NE]) in group C and 19.1 months (95% CI 14.3–NE) in group D.

Conclusion

In the first-line and subsequent-line settings, serplulimab plus HLX04 and serplulimab monotherapy, respectively, showed a manageable safety profile together with encouraging efficacy in patients with advanced HCC.

 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 humanizing its Fab regions and minimizing its glycan contents to generate HLX07 to reduce the immunogenicity and maintain high affinity of the product. As of now, Henlius holds patents of HLX07 in several jurisdictions including China, the United States, the European Union, Australia, and Japan. Moreover, Henlius has received clinical trial approvals for HLX07 in China and the United States. 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 ESCC, sqNSCLC and cutaneous squamous cell carcinoma (CSCC). 

HLX10HLX07-sqNSCLC-201

Title

First-line HLX07 Plus Serplulimab With or Without Chemotherapy Versus Serplulimab Plus Chemotherapy in Advanced/Recurrent Squamous Non-small Cell Lung Cancer: a Phase 2 study

Study design

This randomised, multicentre phase 2 study consisted of 4 parts and assessed different combinations of HLX07 (at various doses), serplulimab, and chemo. Part 3 explored the preliminary efficacy of the three-drug combination and is presented below. Patients with stage IIIB/IIIC or IV squamous non-small cell lung cancer (sqNSCLC) that could not be treated with surgery or radiation therapy and had not received prior systemic therapy were enrolled and randomised 1:1 to receive intravenous HLX07 at 800 mg (group A) or 1000 mg (group B), combined with serplulimab (300 mg) and chemo (carboplatin and nab-paclitaxel), Q3W. The primary endpoints were IRRC-assessed ORR and PFS per RECIST 1.1.

Results

As of 27 June 2023, 12 patients were enrolled and randomly assigned to group A (n=6) and group B (n=6) in part 3. The median age was 64 years. 11 (91.7%) patients were male. 10 (83.3%) patients had stage IV disease. With a median follow-up of 3.5 months, investigator-assessed unconfirmed ORR per RECIST 1.1 was 83.3% (95% CI 35.9–99.6) in group A and 66.7% (95% CI 22.3–95.7) in group B. Disease control rate was 100.0% (95% CI 54.1–100.0) in both groups. 2 (33.3%) patients in group A and 1 (16.7%) in group B had serious treatment-emergent adverse events (TEAEs). 1 (16.7%) patient in group B reported a grade 3 adverse event of special interest (AESI) with dermatitis acneiform; no grade 4–5 AESI occurred. No TEAE leading to death was reported.

Conclusion

First-line HLX07 plus serplulimab and chemo conferred encouraging antitumour efficacy with a manageable safety profile in patients with advanced sqNSCLC and warrants further investigation.

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 single-arm, open-label, multicentre phase 2 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 were enrolled to receive intravenous HLX07 at 1500 mg (group A) or 1000 mg (group B), Q3W in part 1. The primary endpoint was independent radiological review committee (IRRC)-assessed objective response rate (ORR) per RECIST 1.1. Secondary endpoints included other efficacy measures, safety, pharmacokinetics, immunogenicity, and quality-of-life assessment.

Results

As of 2 July 2023, 31 patients were enrolled and assigned to group A (n=21) and group B (n=10) in part 1. The median age was 60 years; 16 (51.6%) patients were male. Among the 29 efficacy evaluable patients (21 ingroup A and 8 in group B), the median follow-up duration was 9.6 months and 3.1 months in the respective groups. IRRC-assessed unconfirmed ORR was 23.8% (95% CI 8.2–47.2) in group A and 62.5% (95% CI 24.5–91.5) in group B. IRRC-assessed median PFS was 3.6 months (95% CI 1.4–5.9) in group A and not reached in group B. Median OS was not reached in either group. Among the 31 patients who received study treatment, grade ≥3 treatment-related adverse events (TRAEs) occurred in 8 (38.1%) and 2 (20.0%) patients in group A and B, respectively, most commonly hypomagnesaemia (14.3% vs. 10.0%) and rash (4.8% vs. 10.0%). No TRAE leading to death was reported.

Conclusion

HLX07 monotherapy demonstrated encouraging antitumour efficacy and was well-tolerated in patients with advanced CSCC.

HLX26 

HLX26 is a human mAb targeting LAG-3 extracellular domains, which developed independently by Henlius. HLX26 can block the LAG-3-mediated signaling pathway to restore the killing function of T cells. Pre-clinical studies proved that HLX26 has the anti-tumour effect and favorable tolerability and safety. Furthermore, in vitro and animal studies showed that HLX26 in combination with serplulimab has a significant synergistic effect in anti-tumour. These results lay the foundation for further clinical studies on combination usage. As of now, the first patients have been dosed in two phase 2 clinical trials of serplulimab in combination with HLX26, respectively for the treatment of metastatic colorectal cancer (mCRC) as well as advanced non-small cell lung cancer (NSCLC). 

HLX26-002

Title

Safety, Preliminary Efficacy, and Pharmacokinetics of HLX26 plus Serplulimab in Advanced Solid Tumours: an Open-label, Dose-escalation Phase 1 Study

Study design

This was a single-centre, open-label, dose-escalation phase 1 study. Patients with histologically or cytologically confirmed advanced/metastatic solid tumours that had failed or could not receive standard therapies were enrolled and received intravenous HLX26 at three dose levels (500, 800, 1600 mg) plus serplulimab (300 mg) Q3W, following a “3+3” design. The primary endpoint was dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) within three weeks after the first administration of HLX26 (i.e. the DLT observation period). Secondary endpoints included safety, preliminary efficacy, pharmacokinetics, and immunogenicity.

Results

As of 19 July 2023, 9 patients with primary stage IV non-small cell lung cancer (n=4, 44.4%), small cell lung cancer (n=2, 22.2%), gastric cancer (n=1, 11.1%), cervical cancer (n=1, 11.1%), or endometrial cancer (n=1, 11.1%) were enrolled and received HLX26 at 500 mg (n=3), 800 mg (n=3), or 1600 mg (n=3), in combination with 300 mg serplulimab. The median age was 66 years, and 6 (66.7%) patients were male. All patients experienced treatment-emergent adverse events (TEAEs); all TEAEs that occurred during the DLT observation period were grade 1 or 2. One patient in the 800 mg group reported grade 3 or 4 drug-related asthenia, pain, and neutrophil count decreased. No DLT was reported and the MTD was not determined yet. Among the 8 efficacy evaluable patients, none had achieved complete or partial response; 3 (37.5%) patients (one in each group) had a best overall response of stable disease.

Conclusion

No new safety signals were observed for the different doses of HLX26 in combination with serplulimab. HLX26 plus serplulimab was safe and well tolerated in patients with advanced solid tumours who had failed or could not receive standard therapies.