ARTICLES

Investigational New Drugs

Novel Anti-Cancer Therapeutics and Therapies

December 19, 2018

Safety, tolerability, and pharmacology of AB928, a novel dual adenosine receptor antagonist, in a randomized, phase 1 study in healthy volunteers

Lisa Seitz, Lixia Jin, Manmohan Leleti, Devika Ashokm, Jenna Jeffrey, Aimee Riegerm, Renger G. Tiessen, Gerhard Arold, Joanne B. L. Tan, Jay P. Powers, Matthew J. Walters, Joyson Karakunnel

Adenosine suppresses antitumor immune responses via A2a and A2b receptors expressed on intratumoral immune cells. This effect is mediated by increased cyclic adenosine 5′-monophosphate (AMP) levels and phosphorylation of cyclic AMP response element binding protein (CREB). We conducted a phase 1, placebo-controlled, single-ascending-dose (SAD) and multiple-ascending-dose (MAD) study to assess the safety, tolerability, pharmacokinetics (PK), including food effect (FE), and pharmacodynamics (PD) of oral AB928, a novel dual A2aR/A2bR antagonist, in healthy volunteers.

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BioWorld

The news source of record covering the development of innovative human therapies
Actionable Intelligence • Incisive Analysis

June 20, 2018 – Volume 29, No. 119

Adenosine dreams fueling new approaches in cancer; Arcus embarks on phase I

By Randy Osborne, Staff Writer

Although Merck & Co. Inc. continues to chalk up investor-pleasing sales with Keytruda (pembrolizumab) and Bristol-Myers Squibb Co. (BMS) keeps doing well with Opdivo (nivolumab), researchers have yet to strike upon the best combinations with other agents.

The prospect of using an oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor took a hit in April when Incyte Corp. and Kenilworth, N.J.-based Merck reported that the pivotal phase III Echo-301/Keynote-252 study testing Incyte’s epacadostat paired with Keytruda in individuals with unresectable or metastatic melanoma failed a review by the external data monitoring committee (DMC).

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