CHISHIKI

Development

AZD4635, a novel oral adenosine A2A receptor antagonist, shows clinical activity as a monotherapy or in combination with Imfinzi® (durvalumab) in patients with advanced solid tumors (AACR 2019)

By AstraZeneca | Apr 14, 2019

Conference

AACR Annual Meeting 2019
29 March – 3 April 2019
Atlanta, U.S.
American Association for Cancer Research
Conference Website

Summary

AstraZeneca presented new clinical data from its Phase 1a study with AZD4635, a next-generation immuno-oncology candidate, as a single agent and in combination with the PD-L1 antibody durvalumab, in patients with advanced solid tumors, at the 2019 American Association for Cancer Research (AACR) Annual Meeting in Atlanta, USA (29 March to 3 April 2019).

AZD4635 is a potent and selective, orally available, small molecule adenosine 2A receptor (A2AR) antagonist discovered by Sosei Heptares and exclusively licensed to AstraZeneca in 2015. Adenosine signalling is a normal process preventing autoimmunity that is co-opted by tumors as an immune escape mechanism. The adenosine pathway is increasingly recognized as critical to tumor suppression and represents a new frontier within immuno-oncology.

Poster Summary

The poster (abstract #CT026) was entitled “Evidence of immune activation in the first-in-human Phase 1a dose escalation study of the adenosine 2a receptor antagonist, AZD4635, in patients with advanced solid tumors,” and reported the following:

  • Early clinical activity was observed with AZD4635 monotherapy or in combination with the anti-PD-L1 antibody durvalumab in patients with advanced solid malignancies
    • Three confirmed responses were observed in eight RECIST evaluable subjects with metastatic castration-resistant prostate cancer (mCRPC) treated with monotherapy AZD4635 (1 PR) or combination with durvalumab (1CR + 1PR)
    • Stable disease of >6 months was also observed in patients with other tumor types, including head & neck, bladder, gastrointestinal cancers and sarcoma
  • Biomarker analysis revealed increased gene expression consistent with immune activity (dendritic cell activation, antigen presentation and cytotoxic T cell activation), as well as increase in T cell repertoire following AZD4635 therapy
  • AZD4635 was well tolerated at 100mg daily as both monotherapy and with durvalumab
  • Most common adverse events (>15%) attributed to AZD4635 monotherapy included Grade 1/2 nausea, fatigue, vomiting and dizziness
  • The trial has been expanded to further evaluate AZD4635 in both immune checkpoint naïve and refractory patients

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