86P - Validation of the Gustave Roussy Immune (GRIm) score in patients treated with bispecific CD3 T cell engagers in phase I clinical trials

Background

The Gustave Roussy Immune (GRIm)-Score considers neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point blockers (ICBs). According to their GRIm-score, patients can be classified as low risk (GRIm-score 0 or 1) or as high risk (GRIM-score 2 or 3). We aimed to determine whether it could be used as a prognostic tool for patients treated in phase I clinical trials with bispecific CD3 T cell engagers.

Methods

A retrospective analysis on overall survival (OS) and progression free survival (PFS) was performed on all patients treated with bispecific CD3 T cell engagers in phase I clinical trials at DITEP between July 2018 and July 2022, alone or in combination with ICB. Estimations of OS and PFS were made using the Kaplan Meier method and comparisons between low and high-risk patients were done using log-rank test. The power of the GRIm-score was analyzed using Harrell’s C-index to determine its predictive ability.

Results

A total of 67 patients with metastatic solid cancer or hematological malignancy was included. Median age was 62 years old (range 42-78), 47 patients were men (70%) and 20 were women (30%). The most common tumor types were prostate cancer (33%), lymphoma (25%) and small cell lung carcinoma (24%). The median number of previous lines of treatment was 4 (range : 1-9). Most of the patients presented a low GRIm-score (80.5%) at baseline : 0 in 46% of the patients and 1 in 34,5% . A high GRIm-score was found in 19.5% of the patients: 2 in 18% and 3 in 1.5%. A low GRIm-score was associated with better OS and PFS (HR: 0.40; 95% CI: 0.19-0.84, p = 0.01 and HR: 0.36; 95% CI: 0.18-0.7, p = 0.002 respectively) in patients treated with bispecific CD3 T cell engagers. The median OS was 17.3 months for low-risk patients and 4.5 months for high risk. The median PFS was 2.8 months for low risk GRIm and 1.2 month for high risk. The Harrel’s C index for OS was 0.60 and 0.58 for PFS.

Conclusions

The GRIm-score was designed for patients treated with ICB. It can be used to select patients for bispecific CD3 T cell engagers phase I clinical trials. It has prognostic impact on PFS and OS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Gustave Roussy.

Funding

Has not received any funding.

Disclosure

V. Goldschmidt: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies, BeiGene, BicycleTx, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Celgene Corporation, Chugai Pharmaceutical, Clovis Oncology, Cullinan-Apollo, Curevac, Daiichi Sankyo, Debiopharm, Eisai, Eli Lilly, Exelixis, Faron Pharmaceuticals, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm, Loxo Oncology, Lytix Biopharma, MedImmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Molecular Partners, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology, Oncoethix, Oncopeptides, Orion Pharma, Ose Pharma, Pfizer, PharmaMar, Pierre Fabre, Medicament, Roche, Sanofi Aventis, Seattle Genetics, Sotio, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Turning Point Therapeutics, Xencor; Financial Interests, Institutional, Proprietary Information: Lilly France; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. J. Michot: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, Astra Zeneca, Aveo, Basilea Pharmaceutica Internationa, Bayer Healthcar, Bbb Technologies, BeiGene, BicycleTx, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical, Clovis Oncology, Cullinan-Apollo, Curevac, Daiichi Sankyo, Debiopharm, Eisai, Eli Lilly, Exelixis, Faron Pharmaceuticals, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium, 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, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Ose Pharma, Pfizer, PharmaMar, Pierre Fabre, Medicament, Roche, Sanofi Aventis, Seattle Genetics, Sotio, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Turning Point Therapeutics, Xencor; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. K. Ouali: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies Bv, BeiGene, BicycleTx; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, R. F. Danlos: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies Bv, BeiGene, BicycleTx; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. P. Martin Romano: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, Astra Zeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies Bv, BeiGene, BicycleTx; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. P. Vuagnat: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies Bv, BeiGene, BicycleTx; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. A. Bernard-Tessier: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Other, Travel fees: Orion, Bayer; Financial Interests, Institutional, Advisory Board: Novartis; Non-Financial Interests, Personal, Principal Investigator: Amgen. A. Gazzah: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies Bv, BeiGene, BicycleTx; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. R. Bahleda: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies Bv, BeiGene, BicycleTx; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, Eisai; Financial Interests, Personal, Advisory Board: Basilea, Tahio, Relay Theraeutics, QED Therapeutics, Debiopharm; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator, M19-345: AbbVie; Non-Financial Interests, Personal, Principal Investigator, CO42216: Roche; Non-Financial Interests, Personal, Principal Investigator, MCLA-158: Merus; Non-Financial Interests, Personal, Principal Investigator, SGNB6A: Seatle Genetics; Non-Financial Interests, Personal, Principal Investigator, TAS-120-202: Tahio; Non-Financial Interests, Personal, Principal Investigator, Krystal-10: Mirati; Non-Financial Interests, Personal, Principal Investigator, ADP-0033: Adaptimmune; Non-Financial Interests, Personal, Principal Investigator, ACT16902: Sanofi; Non-Financial Interests, Personal, Principal Investigator, C4201002: Pfizer; Non-Financial Interests, Personal, Principal Investigator, RLY-4008: Relay Therapeutics; Non-Financial Interests, Personal, Principal Investigator, CC-90011: Celgene/BMS; Non-Financial Interests, Personal, Principal Investigator, Loxo-IDH: Loxo/Lilly; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca. A. Marabelle: Financial Interests, Personal, Advisory Board: Gritstone, Innate Pharma, Neogene, Deka Biosciences, Hotspot Therapeutics, Johnson & Johnson, Depth Charge, Bioline Rx, Clover Biopharmaceuticals, Grey Wolf Therapeutics, Lytix Biopharma, RedX Pharma, HiFiBiO Therapeutics, ImCheck Therapeutics, Shattuck Labs, Marengo Therapeutics, PegaOne; Financial Interests, Personal, Other, Associate Editor: European Journal of Cancer; Financial Interests, Personal, Stocks/Shares: HiFiBiO Therapeutics, Deka Biosciences, HotSpot Therapeutics, Shattuck Labs; Financial Interests, Institutional, Research Grant: BMS, Astra Zeneca, Sanofi; Financial Interests, Institutional, Invited Speaker: IMCheck, SOTIO, Roche/Genentech, MSD, BMS, OSE Immunotherapeutics, Eisai, Pierre Fabre, Adlai Nortye, Molecular Partners; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Funding: Transgene; Non-Financial Interests, Personal, Other, Associate Editor: IOTECH Journal; Non-Financial Interests, Institutional, Product Samples: BMS, IDERA, MSD, Transgene; Non-Financial Interests, Personal, Leadership Role: Société Française d'Immunothérapie des Cancers; Non-Financial Interests, Personal, Member: Society for Immunotherapy of Cancer, American Association for Cancer Research, American Society for Clinical Oncology; Other, Personal, Other, Consultant: Third Rock Ventures, Guidepoint; Other, Personal, Other, Advisor: Medicxi. S. Postel-Vinay: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies Bv, BeiGene, BicycleTx, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. C. Massard: Other, Personal, Other, Christophe Massard: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion Principal/sub-Investigator of Clinical Trials for AbbVie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo Pharmaceuticals, Bayer, BeiGene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 Biomedecine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, MedImmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides, Orion, Pfizer, PharmaMar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor Company. V. Ribrag: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies Bv, BeiGene, BicycleTx; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. S. Ponce Aix: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies Bv, BeiGene, BicycleTx; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. S. Champiat: Financial Interests, Personal, Invited Speaker: Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck, Merck Serono, Novartis and Roche; Financial Interests, Personal, Other, Principal Investigator of Clinical Trials: AbbVie, Amgen, Boehringer Ingelheim, Cytovation, Eisai, Imcheck Therapeutics, Molecular Partners, Merck, Ose Pharma, Pierre Fabre, Sanofi Aventis, Sotio, Transgene; Financial Interests, Personal, Advisory Board: Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, Celanese, Domain Therapeutics, Ellipses Pharma, Genmab, Immunicom, Nanobiotix, Nextcure, Oncovita, Pierre Fabre, Seagen, Tatum Bioscience, Tollys SAS, UltraHuman8; Financial Interests, Personal, Other, Travel and congress: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Ose Pharma, Roche, Sotio; Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP) =Principal/sub-Investigator of Clinical Trials: Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Adaptimmune, AdlaiAstex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies Bv, BeiGene, BicycleTx, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Casi Pharmaceuticals, Celgene Corporation, Cellcentric, Chugai Pharmaceutical, Cullinan-Apollo, Curevac, Daiichi Sankyo, Debiopharm, Eisai, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche, Imcheck Therapeutics, Incyte Corporation, Imcheck Therapeutics, Incyte Corporation, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium, Janssen Cilag, Janssen Research Foundation, Janssen R&D, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, MedImmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Molecular Partners, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Genomics, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre Medicament, Relay Therapeutics, Roche, Sanofi Aventis, Seattle Genetics, Sotio, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Transgene, Turning Point Therapeutics, Xencor; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP) =Research Grants: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Product Samples, As part of the Drug Development Department (DITEP) =Non-financial support (drug supplied): AstraZeneca, BMS, Boehringer Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. C. Baldini: Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca, Aveo, Basilea Pharmaceutica International, Bayer Healthcare, Bbb Technologies Bv, BeiGene, BicycleTx, 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, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium, 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, 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, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Turning Point Therapeutics, Xencor; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, Drug supplied: AstraZeneca, Bayer, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. All other authors have declared no conflicts of interest.