Date: 2016-07-06
Type of information: Treatment of the first patient
phase: 1
Announcement: treatment of the first patient
Company: AstraZeneca (UK)
Product: AZD4635 ( HTL1071) and durvalumab (MEDI4736)
Action
mechanism: adenosine A2A receptor antagonist/monoclonal antibody. Tumour cells have developed mechanisms to evade the immune system, including through the production of a natural molecule called adenosine. By stimulating A2A receptors, adenosine stops T-cells within the immune system from proliferating and reduces their ability to destroy cancer cells. Blocking A2A receptors can therefore promote the anti-cancer response of T-cells within in the tumour microenvironment. AZD4635 ( HTL1071) is an orally available, small molecule adenosine A2A receptor antagonist, and the lead candidate in a portfolio of A2A antagonists discovered by Heptares using its proprietary structure-based drug design platform. This portfolio was licensed to AstraZeneca in August 2015 for development and commercialisation across a range of cancers, with an associated R&D collaboration designed to discover further A2A antagonists for development in cancer immunotherapy. Durvalumab (MEDI4736) is a human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumour’s immune-evading tactics. This antibody is directed against B7-H1, have been shown to block the interaction between B7-H1 and its receptors, PD-1 and CD80 (B7-1). This blockade may help to overcome the immunosuppressive effects of B7-H1 on anti-tumor T cells.
Disease: advanced solid malignancies, non small cell lung cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This phase I, open-label, multicenter study is a trial of continuous oral dosing of AZD4635 administered as a single agent and then in combination with a PD-L1 antibody, durvalumab. The study design allows an escalation of dose with intensive safety monitoring to ensure the safety of the patients. The primary objective of the study is to determine the maximum tolerated dose of AZD4635 in combination with durvalumab. (NCT02740985)
Latest
news: * On July 6, 2016, Heptares Therapeutics, a wholly-owned subsidiary of Sosei Group, announced it has been notified by its partner AstraZeneca that the first subject has been dosed with immuno-oncology candidate HTL1071 (AZD4635) in a Phase 1 clinical study, triggering a $10 million payment from AstraZeneca. This first-in-human study is being conducted by AstraZeneca in approximately 50 patients with advanced solid malignancies and with non-small cell lung cancer. The primary objective is to determine the maximum tolerated dose (MTD) of HTL1071 alone and in combination with durvalumab (MEDI4736), an investigational human monoclonal antibody directed against PDL1. Pending the determination of the MTD, a Phase 2 trial is planned to investigate further the safety, tolerability, pharmacokinetics and anti-tumour activity of the selected doses.
