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.
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 responseEVEREST-1: A seamless phase 1/2 study of A2B530, a carcinoembryonic antigen (CEA) logic-gated Tmod CAR T-cell therapy, in patients with solid tumors associated with CEA expression also exhibiting human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH).
Molina J, Simeone D, Smith C, Welling T, Kirtane K, Grierson P, Morelli M, Hecht J, Patel S, Locke F, Weng W, Fakih M, Vong J, Liechty K, Ng E, Welch J, Maus M, Maloney D, Go W, Punekar S. EVEREST-1: A seamless phase 1/2 study of A2B530, a carcinoembryonic antigen (CEA) logic-gated Tmod CAR T-cell therapy, in patients with solid tumors associated with CEA expression also exhibiting human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH). Journal Of Clinical Oncology 2024, 42: tps2698-tps2698. DOI: 10.1200/jco.2024.42.16_suppl.tps2698.Peer-Reviewed Original ResearchOff-tumor toxicityT-cell therapyCAR-T cell therapyChimeric antigen receptorHLA-A*02T cellsCarcinoembryonic antigenHLA LOHNormal cellsCEA expressionSolid tumorsRecommended phase 2 doseLack of tumor-specific targetsNon-small cell lungDose-escalation portionPhase 2 doseDose-expansion phaseT-cell engagersObjective of Phase 1Tumor-specific targetingTreating solid tumorsT cell receptorOn-targetBayesian optimal interval designCheckpoint inhibitorsEVEREST-2: A seamless phase 1/2 study of A2B694, a mesothelin (MSLN) logic-gated Tmod CAR T-cell therapy, in patients with solid tumors that show MSLN expression and human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH).
Punekar S, Hecht J, Smith C, Simeone D, Dorigo O, Boyd L, Kirtane K, Ward J, Locke F, Morelli M, Block M, Eskander R, Langeberg W, Liechty K, Ong G, Go W, Maloney D, Maus M, Welch J, Molina J. EVEREST-2: A seamless phase 1/2 study of A2B694, a mesothelin (MSLN) logic-gated Tmod CAR T-cell therapy, in patients with solid tumors that show MSLN expression and human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH). Journal Of Clinical Oncology 2024, 42: tps2699-tps2699. DOI: 10.1200/jco.2024.42.16_suppl.tps2699.Peer-Reviewed Original ResearchChimeric antigen receptorOff-tumor toxicityT-cell therapyCAR-T cell therapyMesothelin expressionT cellsHLA-A*02Solid tumorsNormal cellsChimeric antigen receptor T cellsRecommended phase 2 doseCAR T cell activityLack of tumor-specific targetsNon-small cell lung cancerCryopreserved T cellsMajor body cavitiesPhase 2 doseDose-expansion phaseObjective of Phase 1Tumor-specific targetingCell lung cancerSolid tumor typesFirst-in-humanT cell activationOn-target