Alvin Luk

Title: Global phase 3 trial of first China-manufactured trastuzumab biosimilar HLX02 efficacy and safety endpoints for metastatic breast cancer
Time: 15:50 - 16:20


Dr. Alvin Luk is the Senior Vice President and Chief Medical Officer at Shanghai Henlius Biotech, Inc., a global biopharmaceutical company specializing in the discovery, development, manufacturing and commercialization of high-quality biologics to treat a range of chronic and life-threatening diseases. Dr. Luk has over 27 years of experience in global drug development, strategic portfolio management and clinical leadership. Prior to joining Shanghai Henlius Biotech, Inc., he served as the Head of Clinical Research and Operations at Spark Therapeutics, a fully integrated gene therapy company receiving the first US FDA-approved gene therapy product, where he oversaw the global clinical development and operations of several AAV gene therapy programs in ophthalmology, haematology and neurology. Previously, he held a number of executive management positions at companies such as Biogen – Haemophilia Unit, Bayer Healthcare, Avigen (acquired by Sanofi Genzyme) and Tularik (acquired by Amgen). He served on the Clinical Design Committee for rare disease at the U.S. Food and Drug Administration focusing on adaptive clinical trial design to shorten drug development timeline between 2006 and 2009. Until 2003, his early researches were primarily investigating gene regulation and expression with the emphasis on rare diseases, oncological diseases and regenerative medicines. Under his leadership in drug development, he has won regulatory approvals and was instrumental in bringing 16 products from first-in-human trials to marketing approvals as of today. Dr. Luk has published more than 60 book chapters, scientific and medical articles in highly regarded peer-reviewed journals, including New England Journal of Medicine, Nature, Cell, and Science, and is an inventor on over 9 patent applications. Dr. Luk holds an M.B.A. from the Harvard Business School. He is ACRP-certified in clinical research and received his Ph.D. in Neuroscience from the University of California San Francisco Medical School (UCSF).

Research Interest


Background: The introduction of trastuzumab in combination with chemotherapy has significantly improved clinical outcomes for patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer. HLX02 was developed as a trastuzumab biosimilar with the potential to increase market competition and treatment accessibility in China and around the world.

Methods: We conducted a randomised, double-blind, parallel-controlled equivalence study (HLX02-BC01; NCT03084237 and EudraCT: 2016-000206-10) investigating the efficacy and safety profiles of HLX02 and European Union-sourced (EU-)trastuzumab in HER2+ recurrent or previously-untreated metastatic breast cancer patients at 89 study centres in China, Philippines, Poland and Ukraine. Eligible women were aged ?18 years, had histologically confirmed HER2+ breast cancer, an ECOG performance status of 0-1, and estimated life expectancy ?3 months. Patients were randomised at 1:1 to receive an intravenous dose of 8 mg/kg of HLX02 or EU-trastuzumab with docetaxel on Day 1-Cycle 1 followed by a dose of 6 mg/kg every 3 weeks in 3-weekly cycles for up to a maximum of 12 months. The primary endpoint was best overall response rate at Week 24 (ORRwk24) evaluated by blinded central imaging review. Secondary endpoints included clinical benefit rate (CBR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS), safety outcomes with immunogenicity and incidence of adverse events up to 12 months. 

Results: Of 1046 patients enrolled, 649 were randomly allocated to receive HLX02 (n=324) or EU-trastuzumab (n=325). The ORR was 71.0% (230 of 324 patients; 95% CI: 66.0, 75.9) for HLX02 and 71.4% (232 of 325 patients; 95% CI: 66.5, 76.3) for EU-trastuzumab with no statistical difference observed between the two treatment groups (p=0.952) which was completely contained within the predefined equivalence boundaries of ±13.5%. The difference in ORR between the 2 treatments was 0.4 (95% CI: -7.4, 6.6). Safety outcomes and immunogenicity were similar between the treatment groups at Week 24 (table below).

Conclusion: The use of HLX02 compared with EU-trastuzumab resulted in an equivalent ORR at Week 24. All secondary efficacy and safety analyses at Week 24 supported the conclusion of therapeutic equivalence; HLX02 does not demonstrate new safety signals in comparison with EU-trastuzumab. Further study results at Month 12 will be reported when the study is unblinded in September. These results have been submitted to National Medical Product Administration (NMPA) and EMA for review to support marketing approval of HLX02 in China and Europe.