2024
662 A phase1 study of autologous engineered CD4+ and CD8+ T cells, HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR; CD8α/β coreceptor and a FAS41BB switch receptor in patients with solid tumors
Mitchell S, Khan B, Payumo F, Gabriela Chiorean E, Gahvari Z, Randolph Hecht J, Hurwitz M, Leidner R, Lenz H, Pelster M, Schoenfeld A, Punekar S, Zhao D, Basu S, Nagorsen D. 662 A phase1 study of autologous engineered CD4+ and CD8+ T cells, HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR; CD8α/β coreceptor and a FAS41BB switch receptor in patients with solid tumors. 2024, a759-a759. DOI: 10.1136/jitc-2024-sitc2024.0662.Peer-Reviewed Original ResearchInitial data from a phase 1, first-in-human clinical trial for T-Plex, a multiplexed, enhanced T cell receptor-engineered T cell therapy (TCR-T) for solid tumors.
Thomas S, Pico B, Henick B, Leidner R, Samhouri Y, Isaacs J, Weiss J, Hurwitz M, Grewal J, Luke J, Chattopadhyay S, Wang Y, Motta M, Murray J, Barton D, Pinchasik D, MacBeath G, Moser J. Initial data from a phase 1, first-in-human clinical trial for T-Plex, a multiplexed, enhanced T cell receptor-engineered T cell therapy (TCR-T) for solid tumors. Journal Of Clinical Oncology 2024, 42: 2542-2542. DOI: 10.1200/jco.2024.42.16_suppl.2542.Peer-Reviewed Original ResearchT-cell receptor-engineered T-cell therapyLoss of heterozygositySolid tumorsHLA-A*02:01HLA matchingHLA allelesPatients evaluated to dateFirst-in-human clinical trialDose level 1Dose level 3Pre-identify patientsTarget HLA alleleAntitumor T cellsT-cell therapyLoss of heterozygosity testingT-cell attackMaster protocolProportion of patientsScreening protocolCombination of HLAHLA LOHHLA lossImmunosuppressive microenvironmentMAGE-A1HLA typingAFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors.
Mitchell S, Khan B, Payumo F, Chiorean E, Gahvari Z, Hecht J, Hurwitz M, Leidner R, Lenz H, Pelster M, Punekar S, Schoenfeld A, Zhao D, Vallaster M, Nagorsen D. AFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors. Journal Of Clinical Oncology 2024, 42: tps8650-tps8650. DOI: 10.1200/jco.2024.42.16_suppl.tps8650.Peer-Reviewed Original ResearchOptimal biological doseCD8+ T cellsAutologous CD4+Advanced/metastatic solid tumorsT cellsSolid tumorsSwitch receptorsDose expansionDose escalationCD4+Transgenic TCRMechanism of actionDose-limiting toxicity observation periodRecommended phase 2 doseT cell cytotoxic activityIncreased T cell activationCD4+ T cellsHelper T cell responsesPreventing T cell exhaustionPost-treatment follow-up periodChimeric switch receptorsPhase 2 doseImmunosuppressive tumor microenvironmentT cell exhaustionDuration of responseCD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma
Pal S, Tran B, Haanen J, Hurwitz M, Sacher A, Tannir N, Budde L, Harrison S, Klobuch S, Patel S, Meza L, Dequeant M, Ma A, He Q, Williams L, Keegan A, Gurary E, Dar H, Karnik S, Guo C, Heath H, Yuen R, Morrow P, Agarwal N, Srour S. CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma. Cancer Discovery 2024, 14: of1-of14. PMID: 38583184, PMCID: PMC11215406, DOI: 10.1158/2159-8290.cd-24-0102.Peer-Reviewed Original ResearchClear cell renal cell carcinomaChimeric antigen receptorCAR-T cellsT-cell therapyCell renal cell carcinomaRenal cell carcinomaT cellsCell carcinomaSolid tumorsAllogeneic CAR-T cell therapyChimeric antigen receptor T cellsAdvanced clear cell renal cell carcinomaAllogeneic CAR-T cellsClinical trialsCAR-T cell productsCAR-T cell therapyTreatment of solid tumorsFirst-in-human clinical trialCAR-T constructsDose-limiting toxicityT cell productionNovel treatment optionsTreatment of clear cell renal cell carcinomaHematologic malignanciesAntigen receptor
2018
NKTR-214 (CD122-biased agonist) plus nivolumab in patients with advanced solid tumors: Preliminary phase 1/2 results of PIVOT.
Diab A, Hurwitz M, Cho D, Papadimitrakopoulou V, Curti B, Tykodi S, Puzanov I, Ibrahim N, Tolaney S, Tripathy D, Gao J, Siefker-Radtke A, Clemens W, Tagliaferri M, Gettinger S, Kluger H, Larkin J, Grignani G, Sznol M, Tannir N. NKTR-214 (CD122-biased agonist) plus nivolumab in patients with advanced solid tumors: Preliminary phase 1/2 results of PIVOT. Journal Of Clinical Oncology 2018, 36: 3006-3006. DOI: 10.1200/jco.2018.36.15_suppl.3006.Peer-Reviewed Original Research