Abstract 119P
Background
The highly selective inhibitor of PI3Kδ, roginolisib (formerly IOA-244), has a favourable safety profile in patients with solid tumours. To better assess this safety profile, we used the Burden of Therapy (BOTh©™) approach.
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 II dose (RP2D) was done using Common Terminology Criteria for Adverse Events (CTCAE). Secondary objectives: PK; PD (e.g., inhibition of CD63 expression on basophils, changes in immune cell subsets in peripheral blood). Analysis of Part B expansion cohorts will be reported at future meetings. An exploratory evaluation BOTh©™analyses were performed to characterize the burden of toxicity especially in patients with uveal melanoma.
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. 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. Using BOTh©™analyses, the main driver for all-cause TEAEs was one patient who showed initial increase of ALT as hepatic tumor lesions progressed. Part A NHL: No TEAEs were observed and the overall TEAEs were similar to those observed in pts with solid tumors.
Conclusions
IOA-244 at the 80 mg dose shows less than 5% of all-cause Grade 3/4 toxicities. In contrast to other PI3Kd inhibitors, long-term administration of IOA-244 (>6 months) was not associated with diarrhoea or hepatic toxicity.
Clinical trial identification
NCT04328844.
Editorial acknowledgement
The authors thank the patients and their families. Also, we thank all study personal at the clinical investigation centers and the LabCorp Drug Development team.
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, Officer: iOnctura; Financial Interests, Personal, Stocks/Shares: iOnctura. L. Van der Veen, C.A. Pickering: Financial Interests, Institutional, Officer: iOnctura SA. T. Hammett, R. Zorrilla: Financial Interests, Institutional, Full or part-time Employment: iOnctura. M. Durini: Financial Interests, Institutional, Member of the Board of Directors: LabCorp. T.R.J. Evans: Financial Interests, Institutional, Advisory Board, Advisory Board for GI cancers and melanoma (immune checkpoint inhibitors): Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker, Invited speaker - GI cancers, melanoma, immunotherapy: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board, Advisory Boards - GI cancers, melanoma: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Invited speaker GI cancer, melanoma: Roche/Genentech; Financial Interests, Institutional, Advisory Board, Advisory Board (Lenvatinib): Eisai; Financial Interests, Institutional, Invited Speaker, Speaker's fees (lenvatinib): Eisai; Financial Interests, Institutional, Advisory Board, advisory board: MSD, AstraZeneca, Medivir, Bayer, Bicycle Therapeutics, Clovis; Financial Interests, Institutional, Invited Speaker, Speaker's fees: MSD, AstraZeneca, Bayer; Financial Interests, Institutional, Advisory Board, Advisory board: Nucana; Financial Interests, Institutional, Invited Speaker, speaker's fees: Nucana; Financial Interests, Institutional, Invited Speaker, speaker's fees (and presentation to potential investors): Medivir; Financial Interests, Personal, Other, Support to attend international conferences: Bristol Myers Squibb, Roche/Genentech, MSD, Nucana, Bayer, Celgene, Pierre Fabre; Financial Interests, Institutional, Advisory Board, Advisory Board for Upper GI Cancer: Ascelia; Financial Interests, Institutional, Advisory Board, Advisory Board for Oesophageal Cancer: Seagen; Financial Interests, Institutional, Invited Speaker, Educational grant (supply of study agents) for investigator-led study and reimbursement of study costs for commercial studies: AstraZeneca; Financial Interests, Institutional, Invited Speaker, reimbursement of study costs for commercial studies: Astellas, Bayer, Adaptimmune, Bristol Myers Squibb, Basilea, Celgene, GSK, Eisai, MSD, Roche, Medivir, Nucana, Starpharma, Immunocore, Novartis, Sapience Therapeutics, MiNa Therapeutics, Lilly, Bicycle Therapeutics, Sierra, CytomX, Beigene, Pfizer, Johnson & Johnson, iOnctura, UCB, Sanofi, Codiak, Avacta, Nurix, T3P; Financial Interests, Institutional, Invited Speaker, support for non-commercial investigator-led study: Verastem; Financial Interests, Institutional, Invited Speaker, reimbursement for costs of commercial studies: Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker, reimbursement of costs of commercial study: Seagen; Non-Financial Interests, Personal, Other, Member of Clinical Experts Review Panel/Clinical Research Committee: Cancer Research UK; Non-Financial Interests, Personal, Member, Cancer Society Member: American Society of Clinical Oncology, America Association for Cancer Research, British Association for Cancer Research, Association of Cancer Physicians (UK), European Association for Cancer Research, International Liver Cancer Association; Non-Financial Interests, Personal, Other, Member of Scientific Advisory Panel: Pancreatic Cancer Research Fund; Non-Financial Interests, Personal, Other, Annual Meeting abstracts committee: International Liver Cancer Association; Non-Financial Interests, Institutional, Product Samples, Supply of investigational and licensed compounds for a non-commercial study for which I'm Chief Investigator: AstraZeneca; Other, Personal, Other, Editor-in-Chief: British Journal of Cancer; Other, Personal, Other, Chair of Independent Data Monitoring Committee for a phase I trial - honorarium payable to the employing institution: Genmab. M. Maio: Financial Interests, Personal, Advisory Board: BMS, Roche, GSK, Sanofi, Alfasigma, Amgen, Sciclone, Eli Lilly, MSD, Incyte, Pierre Fabre, AstraZeneca; Financial Interests, Personal, Stocks/Shares: Epigen, Theravance. All other authors have declared no conflicts of interest.