Abstract 472P
Background
Bispecific T cell engager are anticancer drugs that bind to CD3 and cell surface antigens. We aim to identify variables related to prolonged progression free survival (PFS) in ph I clinical trials evaluating these drugs.
Methods
We included all patients treated with a bispecific T cell engager in a phase I study at DITEP Gustave Roussy between June, 2016 - October, 2021). Tumor growth rate (TGR) was estimated based on RECIST1.1. After labelling pts based on PFS≥180 d, we performed data amplification with Synthetic Minority Oversampling Technique (SMOTE). XGBoost (XGB) model was trained on the amplified dataset with 5-fold cross-validation to select features associated to PFS ≥ 180 d. Selected features were used in multivariate Cox analyses stratified for tumor type to estimate their effect on PFS. An unsupervised Gaussian mixture clustering model (GMM) was then used to group pts according to the features selected by XGB. After verifying that 14 out of 16 pts with PFS ≥ 180 d were in only one (cluster 0) out of the six generated clusters, all other clusters were grouped. To compare clusters, all variables were submitted to univariate analysis (Mann-Whitney U for continuous, chi-squared for categorical variables, correcting p-values by Benjamini-Hochberg FDR).
Results
25 pts were included with a median age of 58 y (IQR 53-66), 15 male (60%), median of four previous lines of treatment (2-5), and primary tumor site in lung (12 pts), GI tract (13 pts). After SMOTE, 9 data points were added. XGB achieved a C-statistic of 0.72 (CI95 0.6-0.84), and selected age, RMH score, TGR after starting treatment, neutrophil-lymphocyte ratio, platelet count (PC), LDH level, serum albumin and c-reactive protein (CRP). Only TGR was significant for PFS (HR 1.42, p 0.01). Factors that differed significantly between clusters were LDH (p<0.01) and CRP (p 0.03). The mPFS was 123 d (CI95 75–188), while mPFS in Cluster 0 was 265 d (83 -435) versus 75 d (28 – 111) in other clusters (p<0.01, log-rank).
Conclusions
Lower inflammatory markers and tumor growth rate after starting bispecific T cell engager might be useful to identify pts with higher mPFS. Larger datasets and external validation are required.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Institut Gustave Roussy.
Funding
Has not received any funding.
Disclosure
J-M. Michot, P. Martin Romano, C. Sarkozy, A. Gazzah, R. Bahleda, F-X. Danlos, A. Hollebecque, A. Marabelle, S. Postel-Vinay, C. Massard, S. Ponce Aix, S. Champiat, C. Baldini: Non-Financial Interests, Institutional, Principal/sub-Investigator of Clinical Trials: Abbvie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, Astra Zeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, BicycleTx Ltd, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Curevac, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium SA, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre, Medicament, Roche, Sanofi Aventis, Seattle Genetics, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Turning Point Therapeutics, Xencor; Financial Interests, Institutional, Research Grants: Astrazeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-financial support (drug supplied): Astrazeneca, Bayer, BMS, Boringher Ingelheim, GSK, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche. C. Baldini: Financial Interests, Personal, Consultant: Bicycle therapeutics, Rising Tide Foundation, and ITEOS; Financial Interests, Personal, Honoraria: GSK, BMS, AZ, Amgen, Sanofi, and MSD (travel accommodation); Financial Interests, Personal, Funding: BMS Foundation. S. Champiat: Non-Financial Interests, Institutional, Principal Investigator: Abbvie, Amgen, Cytovation, Eisai, Imcheck Therapeutics, Molecular Partners Ag, Merck, Ose Pharma, Pierre Fabre, Sanofi Aventis, Sotio A.S, and Transgene; Financial Interests, Personal, Honoraria: Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck, Novartis, and Roche; Financial Interests, Personal, Advisory board: Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, Ellipses Pharma, Oncovita, Seagen, UltraHuman; Financial Interests, Personal, Travel support: AstraZeneca, Bristol Myers Squibb, Merck, Ose Pharma, Roche, and Sotio. All other authors have declared no conflicts of interest.