1. AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced tumors: Preliminary results from ongoing phase I studies
- Author
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Joyson Joseph Karakunnel, Rodolfo Gutierrez, Dominic W. Lai, Wade Berry, Aimee Rieger, Matthew J. Walters, Arvind Chaudhry, Adam Park, Lisa Seitz, Paul de Souza, John D. Powderly, Devika Ashok, Lisa G. Horvath, and Amanda Garofalo
- Subjects
Cancer Research ,Chemotherapy ,Tumor microenvironment ,business.industry ,medicine.medical_treatment ,Anti pd 1 ,Antagonist ,Adenosine receptor antagonist ,Adenosine ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,In patient ,business ,030215 immunology ,medicine.drug - Abstract
2604 Background: AB928, a selective, small-molecule A2aR/A2bR antagonist, potently blocks the immunosuppressive effects of high adenosine concentrations in the tumor microenvironment. Preclinically, combining adenosine receptor inhibition with either chemotherapy or anti-PD-1 resulted in greater tumor control, suggesting AB928 may have additive activity when paired with either of these agents in cancer pts. Methods: Three dose-escalation (3+3 design) studies are assessing the safety, pharmacokinetics (PK), pharmacodynamics, and clinical activity of increasing doses of AB928 (75, 150, 200 mg orally once daily) in combination with: standard pegylated liposomal doxorubicin in triple-negative breast cancer (TNBC) and ovarian cancer (OC); standard mFOLFOX6 in gastroesophageal cancer (GEC) and colorectal cancer (CRC); and AB122 (240 mg every 2 weeks) in various advanced tumors. Following identification of the recommended phase 2 dose of AB928 in combination with chemotherapy or AB122 in dose escalation, the following tumor cohorts may be expanded (15-40 pts/cohort) to further test the combinations: TNBC and OC, GEC and CRC, and renal cell carcinoma. Results: As of 01Feb2019, 9 pts were treated across the 3 studies, and time on treatment ranged from 1-182 days (table). Overall, AB928 combination therapy was well tolerated. Two pts underwent post-baseline disease assessment; both had stable disease. Preliminary data indicate that AB928 PK and adenosine receptor coverage in cancer pts are similar to what was previously assessed in healthy volunteers. AB122 PK and PD-1 coverage are equally unaffected by AB928 co-administration. Updated data, including biomarker data, will be presented at the meeting. Conclusions: Early results showed a favorable safety profile of AB928 combination therapy. All 3 studies are actively recruiting pts. Clinical trial information: NCT03719326; NCT03720678; NCT03629756. [Table: see text]
- Published
- 2019
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