P740: pk, pd and safety of first-in-human, first-in-class phase i trial (aur103-101; bharat) of aur103, an oral cd47 inhibitor, in patients with advanced malignancies

Background: CD47 is a widely expressed receptor well known for its immunoregulatory functions. By interacting with its ligands, including signal regulatory protein α (SIRPα), it promotes escape of cellular phagocytosis of tumor cells by macrophages. AUR103 is an oral small molecule inhibitor of CD47 and is currently in a First in Human Phase 1 Trial (ClinicalTrials.Gov Identifier NCT05607199) Aims: To determine the Optimal Biological Dose (OBD) of single agent AUR103 by evaluating the overall safety, PK and PD of AUR103 in patients with relapsed advanced malignancies. Methods: This is an open-label, Multicentre, Phase I study being conducted in 3 + 3 design. Safety, PK and PD are being evaluated from each cohort, before dose escalation. The First in Human dose was 25 mg BID and there are a total of five pre-planned dose cohorts (25 mg BID; 50 mg BID; 100 mg BID; 200 mg BID and 400 mg BID). Subsequent to determining the OBD of single agent AUR103, combination studies with azacitidine and/or azacitidine/Venetoclax and/or ADCC competent antibodies will be studied in relevant tumor types. Results: As of the submission of the current abstract, both Cohort 1 and Cohort 2 have enrolled 3 patients each. There have not been any DLT or any Grade 3/4 AEs and also no evidence of any haemolytic anaemia of any grade in the first two cohorts. The reported AEs include Grade 1 itching (1/6), Grade 1 pain in legs (2/6), Grade 1 body ache (1/6), Grade 1 loss of appetite (1/6), Grade 1 shoulder pain (1/6), Grade 1 decrease in reticulocyte count (1/6), and Grade 2 drooping of eyelids (1/6). PK showed AUC0-12 of 1685 hr*ng/mL on Day 1 and 3465 hr*ng/mL on Day 15, in Cohort 1. The Cohort 2 PK showed a general dose proportionality with AUC0-12 of 2745 hr*ng/mL on Day 1 and 6669 hr*ng/mL on Day 15, respectively. Within each cohort, the variation in PK has been small. Enrolment in the 3rd cohort (100 mg BID) has been initiated. Summary/Conclusion: AUR103 is a novel First in Class small molecule inhibitor of CD47. The First in Human trial (AUR103-101; BHARAT) is currently enrolling. The preliminary safety in the first two cohorts appears commensurate with “lack of haemolysis” in non-clinical models. PK/PD results suggest that OBD should be reached by Cohorts 4 or 5. Updated results of safety, PK and PD will be presented at the meeting. Keywords: Phase I, AML