Abstract 192P
Background
The highly selective inhibitor of PI3Kδ, IOA-244, has a unique safety and pharmacodynamic profile showing immune modulation in patients with solid tumours.
Methods
IOA-244 was investigated in a two-part FIH study: Part A investigated the safety and pharmacokinetics of continuous daily dosing of IOA-244 at 10, 20, 40 and 80 mg. Primary objective: safety of the anticipated biologically effective dose (BED), or of the recommended phase 2 dose (RP2D). Secondary objectives: PK; PD (e.g., inhibition of CD63 expression on basophils, changes in immune cell subsets in peripheral blood); RECIST 1.1.-based responses; PFS and OS. Exploratory studies: changes in circulating immune cells by mass cytometry (Cytometry by Time of Flight; CyTOF); response assessments by radiomics. Analysis of Part B expansion cohorts will be reported at future meetings.
Results
Part A Solid Tumor: Sixteen patients (pts) were treated in 4 cohorts each with 4 pts. Pts characteristics: uveal melanoma (9/16; 56%), cutaneous melanoma (5/16; 31%) and pleural mesothelioma (2/16; 13%). There were no DLTs or treatment-emergent adverse events (TEAE) leading to study drug dose modification. 7/16 pts (44%) were treated for more than 6 months and had SD during this period. At the estimated IC90 (80 mg QD), patients had improvements of their liver enzymes unless tumour progressed in the liver. Four patients at lower dose levels were increased to 80 mg QD with no additional toxicities. 5/16 were treated after RECIST 1.1-defined PD and 2/4 are still on IOA-244 (>2 years on treatment). The median OS has not been reached. In the UM group 2/9 patients are still on IOA-244 (>18 months on treatment; Median OS: 5.4 - not reached) Part A Follicular Lymphoma: Eight patients were treated at 20 mg (4/4 pts) and 80 mg QD (4/4). No DLT. At 80 mg, there was one PR for 4 months and 1 transient clinical response for 6 weeks. All patients had low circulating blood Tregs during the treatment.
Conclusions
IOA-244 at the 80 mg dose shows less than 5% Grade 3/4 toxicities. In contrast to other PI3Kδ inhibitors, long-term administration of IOA-244 (>6 months) was not associated with diarrhoea or hepatic toxicity.
Clinical trial identification
NCT04328844.
Legal entity responsible for the study
iOnctura SA.
Funding
iOnctura SA.
Disclosure
A.M. Di Giacomo: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: Sanofi. M. Lahn: Financial Interests, Personal, Leadership Role: iOnctura. L. van der Veen: Financial Interests, Personal, Leadership Role: iOnctura. T. Hammett: Financial Interests, Personal, Full or part-time Employment: iOnctura. C.A. Pickering: Financial Interests, Personal, Leadership Role: iOnctura. M. Durini: Financial Interests, Personal, Full or part-time Employment: LabCorp. M. Occhipinti: Financial Interests, Personal, Leadership Role: Radiomics. All other authors have declared no conflicts of interest.