Shanghai, China, May 26th, 2023 –Shanghai Henlius Biotech, Inc. (2696.HK) announced that results from two clinical trials of the company’s self-developed novel products, including HLX07-002, the phase 1b/2 clinical trial of Henlius’ innovative anti- epidermal growth factor receptor (EGFR) monoclonal antibody(mAb) HLX07 for the treatment of advanced solid tumours, and HLX26-001, the phase 1 clinical trial of Henlius’ anti- lymphocyte-activation gene 3 (LAG-3) mAb HLX26 for the treatment of advanced or metastatic solid tumours or lymphomas, were released as online abstract by 2023 American Society of Clinical Oncology (ASCO) Annual Meeting for the first time. Professor Jin Li from Shanghai East Hospital and Professor Jian Zhang from Fudan University Shanghai Cancer Center are the leading principal investigator of HLX07-002 and HLX26-001, respectively.
HLX07 phase 1b/2 clinical trial (HLX07-002)
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. In February 2023, the phase1b/2 clinical trial of HLX07 has been completed in patients with advanced solid tumours. Details of the results presented at 2023 ASCO Annual Meeting are as follows:
Title
Safety and tolerability of HLX07 combined with chemotherapy in patients with advanced solid tumors.(Abstract No. e15001)
Study design
This was a single-center, open-label, dose-escalation phase 1b/2 study. Three fixed-dose chemo-regimens were given together with HLX07: 1) gemcitabine 1000 mg/m2 (on Days 1 and 8) and cisplatin 75 mg/m2 (on Day 1) in 3-week cycles for 4–6 cycles; 2) paclitaxel 80 mg/m2 and carboplatin AUC = 2 (both on Days 1, 8, and 15) in 3-week cycles for 4–6 cycles; and 3) mFOLFOX6 (on Day 1) in 2-week cycles for 6–12 cycles. Patients with metastatic or recurrent advanced solid tumors suitable to be treated with the above chemo-regimens were given HLX07 IV at escalating doses (400, 600, or 800 mg, QW) combined with chemotherapies following BOIN design. The primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary endpoints included safety and preliminary efficacy.
Results
As of August 28, 2022, 56 patients were enrolled; 21 received HLX07 with gemcitabine and cisplatin, 21 received HLX07 with paclitaxel and carboplatin (n = 3 for HLX07 400 and 600 mg, n = 15 for HLX07 800 mg for each chemo-regimen), and 14 received HLX07 with mFOLFOX6 (n = 3 for HLX07 400 and 600 mg, n = 8 for HLX07 800 mg).
No DLT related to HLX07 was reported. The MTD was not reached.
Conclusion
HLX07 was safe and well tolerated when combined with chemotherapy in patients with advance solid tumors.
HLX26 phase 1 clinical trial (HLX26-001)
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 patient has been dosed in a phase 2 clinical trial of serplulimab in combination with HLX26 for the treatment of metastatic colorectal cancer (mCRC). Meanwhile, the investigational new drug application (IND) for a phase 2 clinical trial of serplulimab in combination with HLX26 for the first-line treatment of advanced non-small cell lung cancer (NSCLC) has been approved by the National Medical Products Administration (NMPA). Details of the results presented at 2023 ASCO Annual Meeting are as follows:
Title
Safety, tolerability, and pharmacokinetics of HLX26 (an anti-LAG3 antibody) in patients with advanced or metastatic solid tumors or lymphomas. (Abstract No. e14671)
Study design
This was a first-in-class, multicenter, open-label, dose-escalation phase 1 study. Patients with histologically or cytologically confirmed advanced solid tumors or lymphomas who had failed or were not suitable for standard therapies were enrolled and received HLX26 at five dose levels (60, 150, 300, 500, or 800 mg, Q3W) intravenously. This study followed accelerated titration combined with a “3+3” design. HLX26 was given until disease progression with no clinical benefit, 2 years of treatment, experiencing intolerable toxicity, withdrawal of consent, or death, whichever occurred first. The primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) within DLT observation period, which was 3 weeks after the first dose of HLX26. Secondary endpoints included safety, pharmacokinetic and pharmacodynamic characteristics, preliminary efficacy, immunogenicity, and potential biomarker explorations of HLX26.
Results
As of December 22, 2022, 12 patients with stage IV breast (n = 10, 83.3%) or rectum (n = 2, 16.7%) solid tumors were enrolled and received HLX26 at 60 mg (n = 1), 150 mg (n = 1), 300 mg (n = 3), 500 mg (n = 3), or 800 mg (n = 4). The mean age was 57.5 (range 31–73) years.
No DLT was reported and the MTD was not determined as of yet. Eleven (91.7%) patients experienced treatment-emergent adverse events (TEAEs), most commonly hypercholesterolemia (41.7%), hypertriglyceridemia (25.0%), and hyperuricemia (25.0%). Most TEAEs were grade 1 (n = 8, 66.7%) and 2 (n = 2, 16.7%).
Conclusion
In summary, no new safety signals were observed from 60 mg to 800 mg of HLX26. HLX26 was safe and well tolerated in patients with advanced or metastatic solid tumors.