Early Trial Launched for Promising Lung Cancer Immunotherapy
MEDI4736 is an experimental human monoclonal antibody used against PDL1.
The initiation of a phase 1 trial with the immune-oncology candidate HTL-1071 (AZD4635) has triggered a $10 million milestone payment from AstraZeneca to Heptares Therapeutics.
The trial enrolled approximately 50 patients with advanced solid malignancies and non-small cell lung cancer (NSCLC) to determine the maximum tolerated dose (MTD) of AZD4635 monotherapy, and in combination with durvalumab (MEDI4736).
MEDI4736 is an experimental human monoclonal antibody used against PDL1, while AZD4635 is an orally-available, small molecule adenosine A2A receptor antagonist, and the lead candidate in a portfolio of A2A antagonists.
“The production of adenosine is a recently identified mechanism employed by tumor cells to suppress T cell activity and evade destruction,” said Tim Tasker, chief medical officer at Heptares. “The initiation of this first clinical study in the A2A antagonist immune-oncology program with AstraZeneca is an important milestone for Heptares and we are excited to see how the results from the preclinical studies translate into potential new medicines for cancer patients.
“This is the second program in our partnered pipeline to progress into the clinic, the first being the M1 agonist program, licensed by Allergan, in which 2 novel compounds are undergoing clinical studies as potential new medicines for cognitive impairment in Alzheimer’s disease and other neurological indications.”
Pending the determination of the MTD of AZD4635 alone and in combination with MEDI4736, a phase 2 clinical trial is planned to further investigate the safety, tolerability, anti-tumor activity, and pharmacokinetics of the doses.
“Immuno-oncology is 1 of 4 key oncology platforms for AstraZeneca,” said Susan Galbraith, vice president, head of oncology in AstraZeneca’s Innovative Medicines and Early Development Unit. “In building our immune-oncology portfolio, we believe that blocking adenosine A2A receptor could enhance the efficacy of immune checkpoint inhibition via PDL1, CTLA4, and enhance the activity of CD73 inhibition. This innovative approach could help drive an immune attack on cancers, creating novel treatments with the potential to transform the lives of patients.”