Hutchmed has dosed the first subject in the Phase I clinical trial of oncology drug candidate, HMPL-A83, in patients with advanced malignant neoplasms in China.
HMPL-A83 is an investigational new IgG4-type humanised anti-CD47 monoclonal antibody.
It hinders CD47 attaching to signal regulatory protein (SIRP) α and disturbs the ‘do not eat me’ signal that cancer cells use to prevent themselves from the immune system.
Furthermore, HMPL-A83 is the 13th oncology drug candidate and is the second large molecule drug candidate of the company to enter clinical trials.
The multicentre, open-label trial will analyse the safety, tolerability, pharmacokinetics and initial efficacy of HMPL-A83 in patients with advanced malignant neoplasms.
Dose-limiting toxicity (DLT), safety, tolerability, recommended Phase II dose (RP2D) and maximum tolerated dose (MTD) are the trial’s primary endpoints.
Pharmacodynamics, pharmacokinetics, immunogenicity and initial efficacy profile are the trial’s secondary endpoints.
Hutchmed CEO and chief scientific officer Dr Weiguo Su said: “HMPL-A83 marks a new chapter in our large molecule and immunotherapy exploration.
“It is our thirteenth oncology drug candidate to emerge from our innovative in-house discovery platform and it has significant potential to offer new combination therapy opportunities with our existing small molecule portfolio.
“This approach forms a key part of our multi-pronged strategy to treat cancer and immunological diseases and we are very excited to advance HMPL-A83’s development.”
HMPL-A83 showed a reduced affinity for red blood cells and no induction of hemagglutination, indicating reduced anaemia risk in preclinical studies.
Furthermore, it showed an increased affinity for CD47 antigen on tumour cells as well as robust phagocytosis induction of various tumour cells.
In February this year, the company began a Phase Ib/II trial of HMPL-453 in combination with chemotherapy or toripalimab for advanced solid tumours in China.