41P - Total tumor burden and radiomics to evaluate response in dose escalation studies: Roginolisib (IOA-244), a highly selective PI3Kd inhibitor in metastatic uveal melanoma patients

Background

Due to disease heterogeneity, RECIST v1.1 may underestimate drug efficacy in metastatic uveal melanoma by focusing on a limited set of lesions using 1D measurements. Volumetric Total Tumor Burden (TTB), despite being resource intensive, offers a more comprehensive assessment by evaluating individually all measurable lesions. In addition, radiomics may further predict long-term treatment response by identifying lesion-specific characteristics. This study aims to: (1) demonstrate that RECIST v1.1 and TTB yield different drug efficacy assessments, and (2) show that baseline and delta radiomic features can predict which lesions will have a long-term response to therapy.

Methods

Twenty-three metastatic uveal melanoma patients (11 male, 12 female) were evaluated using RECIST v1.1 and TTB. Lesions were tracked over time, assessing growth and shrinkage. Baseline and delta radiomic features (week 8 vs. baseline) were extracted from lung and liver lesions. Feature reduction was done using the Boruta algorithm, removing low-variance (IQR < 0.1) and highly correlated features (Spearman correlation > 0.9). Univariate (Wilcoxon rank-sum) and multivariate models (GLM and mixed-effects GLM) were applied.

Results

At screening, patients had a median of 31 lesions (range: 2–281), across 20 anatomical sites. RECIST target lesions accounted for a mean of 73% of TTB. In 54% of patients, RECIST and TTB gave different disease classifications (e.g., stable vs. progressive disease). In the lung, 3 baseline and 13 delta features, and in the liver, 5 baseline and 6 delta features statistically differed between responding and non-responding lesions. Multivariate models achieved AUCs of around 0.60-0.65 for baseline features, improving to >0.90 when including delta features.

Conclusions

RECIST v1.1 may not fully capture tumor changes compared to TTB, potentially underestimating treatment efficacy. Baseline and delta radiomic features, particularly shape, intensity and texture, show promise in predicting long-term lesion response. These findings support using volumetric and radiomic analysis for more accurate monitoring of treatment response in metastatic patients.

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, Immunocore; Financial Interests, Personal, Invited Speaker: Sanofi. A. Corsi, N. Sindhwani, A. Rasooli, M.H. Nawaz, F. Belmans: Financial Interests, Personal, Full or part-time Employment: Radiomics.bio. C. C. Meca: Financial Interests, Personal and Institutional, Full or part-time Employment: Radiomics.bio; Financial Interests, Personal and Institutional, Leadership Role, Chief Business Officer: Radiomics.bio; Financial Interests, Personal and Institutional, Ownership Interest: Radiomics.bio; Financial Interests, Personal and Institutional, Stocks or ownership: Radiomics.bio; Financial Interests, Personal and Institutional, Stocks/Shares: Radiomics.bio. M. Maio: Financial Interests, Personal, Advisory Board: BMS, Roche, GSK, Sanofi, Alfasigma, Amgen, Sciclone, Eli Lilly, MSD, Incyte, Pierre Fabre, AstraZeneca, Pfizer, Merck Serono; Financial Interests, Personal, Stocks/Shares: Epigen, Theravance. 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, 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, Advisory Board, advisory board; Chair of Scientific Advisory Council (HCC & MIV-818): Medivir; 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, Coordinating PI, Educational grant (supply of study agents) for investigator-led study and reimbursement of study costs for commercial studies: AstraZeneca; Financial Interests, Institutional, Local PI, reimbursement of study costs for commercial studies: Astellas, Bayer, Basilea, Celgene, GSK, Roche, Medivir, Starpharma, Immunocore, Novartis, Sapience Therapeutics, MiNa Therapeutics, Lilly, Bicycle Therapeutics, Sierra, CytomX, Beigene, Pfizer, Johnson & Johnson, UCB, Codiak, Avacta, Nurix, T3P, Amgen, Moderna; Financial Interests, Institutional, Coordinating PI, reimbursement of study costs for commercial studies: Adaptimmune, Bristol Myers Squibb, Eisai, MSD, Nucana, iOnctura, Sanofi; Financial Interests, Institutional, Local PI, support for non-commercial investigator-led study: Verastem; Financial Interests, Institutional, Local PI, reimbursement for costs of commercial studies: Boehringer Ingelheim; Financial Interests, Institutional, Local PI, reimbursement of costs of commercial study: Seagen; Financial Interests, Institutional, Funding, reimbursement of study costs for commercial studies; lead investigator for infrastructure investment to NHS Research Scotland: BioNTech; Financial Interests, Institutional, Local PI, reimbursement of study sots for commercial studies: Exelixis; 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; 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; Other, Personal, Other, Editor-in-Chief: British Journal of Cancer; Other, Personal, Other, Chair of Independent Data Monitoring Committee for a phase 1 trial - honorarium payable to the employing institution: Genmab; Other, Personal, Other, Chair and panel member, Scientific Evaluation Committee: early phase trials (Amgen, Merck, AstraZeneca); Chair and panel member, CLIP (early phase trial centres) 5-year review: Institut National du Cancer (France); Other, Personal, Other, Panel Member, Pancreas Cancer funding committee, 2023: Fondation ARC; Other, Personal, Other, NHS Research Scotland cancer research network national clinical lead: NHS Research Scotland. M. Lahn: Financial Interests, Personal and Institutional, Leadership Role, Chief Medical Officer: iOnctura SA; Financial Interests, Personal and Institutional, Full or part-time Employment: iOnctura SA. W. Vos: Financial Interests, Personal and Institutional, Full or part-time Employment: Radiomics.bio; Financial Interests, Personal and Institutional, Leadership Role, Chief Executive Officer: Radiomics.bio; Financial Interests, Personal and Institutional, Ownership Interest: Radiomics.bio; Financial Interests, Personal and Institutional, Stocks or ownership: Radiomics.bio; Financial Interests, Personal and Institutional, Stocks/Shares: Radiomics.bio. All other authors have declared no conflicts of interest.