Summary of CD19-CAR constructs in clinical trials
| Institution . | Gene transfer method . | ScFv* . | Costimulatory domain . | Patient populations . | Lymphodepleting chemotherapy . | Infused cell doses . | Responses observed . |
|---|---|---|---|---|---|---|---|
| CHOP3,4 | Lentivirus | FMC63 | 4-1BB | Pediatric ALL; n = 534 | Investigator’s choice | 1.07 × 106 to 17.36 × 106 CAR+ T cells/kg | CR: 50/53 (MRD− in 45/50) 12 mo RFS: 45% 12 mo OS: 78% |
| NCI5 | γ-retrovirus | FMC63 | CD28 | Pediatric ALL; n = 20 | Cy 900 mg/m2 ×1 + Flu 25 mg/m2 ×3 d | 1 × 106 (N = 16) vs 3 × 106 (N = 4) CAR+ T cells/kg | CR: 14/20 (MRD− in 12/14) LFS: 79% at 4.8 mo (MRD− CR patients) OS: 52% at 7.8 mo (all) |
| NCI6 | γ-retrovirus | FMC63 | CD28 | Adult CLL and B-NHL; n = 8 | Cy 60 mg/kg ×2 d + Flu 25 mg/m2 ×5 d | 0.3 × 107 to 3.0 × 107 CAR+ T cells/kg | ORR: 6/8 (CLL, 3/4; FL, 2/3); CR, n = 1 (CLL) and PR, n = 5 |
| NCI7 | γ-retrovirus | FMC63 | CD28 | Adult B-NHL; n = 15 | Cy 60 mg/kg ×1-2 d + Flu 25 mg/m2 ×5 d | 1 × 106 to 5 × 106 CAR+ T cells/kg | CR: 4/7 (refractory DLBCL), 4/6 (indolent B-NHL) |
| MSKCC8-10 | γ-retrovirus | SJ25C1 | CD28 | Adult ALL; n = 469 | Cy or Cy + Flu | 1 × 106 vs 3 × 106 CAR+ T cells/kg | CR: 37/45 (MRD− in 30/36) among evaluable patients 6 mo OS: 65% (all) and 80% (MRD− CR patients) |
| FHCRC11 | Lentivirus | FMC63 | 4-1BB | Adult ALL; n = 29 | Cy or Cy 60 mg/kg ×1 + Flu 25 mg/m2 ×3 d | 2 × 105, 2 × 106, and 2 × 107 CAR+ T cells/kg; 1:1 CD4+:CD8+ | CR: 10/12 (Cy only) and 14/14 (Cy + fludarabine); MRD status unspecified |
| FHCRC12 | Lentivirus | FMC63 | 4-1BB | Adult B-NHL; n = 28 Adult CLL; n = 6 | Cy 60 mg/kg ×1 ± etoposide or Cy 60 mg/kg ×1 + Flu 25 mg/m2 ×3 d | 2 × 105, 2 × 106, and 2 × 107 CAR+ T cells/kg 1:1 CD4+:CD8+ | ORR (B-NHL): 6/12 (CR, n = 1, PR, n = 5 in Cy cohort) and 8/12 (CR, n = 5, PR, n = 3 in Cy + Flu cohort) ORR (CLL): 5/6 (CR, n = 3, PR, n = 2) |
| UPenn13 | Lentivirus | FMC63 | 4-1BB | Adult CLL; n = 14 | Investigator’s choice | 0.14 × 108 to 11 × 108 CAR+ T cells | ORR: 8/14 (MRD− CR, n = 4, PR, n = 4) Median PFS: 7 mo Median OS: 29 mo |
| UPenn14 | Lentivirus | FMC63 | 4-1BB | Adult CLL; n = 26 | Investigator’s choice | 5 × 107 vs 5 × 108 CAR+ T cells | ORR: 9/23 (CR, n = 5, PR, n = 4) |
| UPenn15 | Lentivirus | FMC63 | 4-1BB | Adult B-NHL; n = 24† | Investigator’s choice | 3.08 × 106 to 8.87 × 106 CAR+ cells/kg | ORR: 15/22 (DLBCL, 7/13; FL, 7/7, MCL, 1/2) PFS: 62% at 11.7 mo |
| UPenn14 | Lentivirus | FMC63 | 4-1BB | Adult ALL; n = 12 | Investigator’s choice | 6.5 × 106 to 8.45 × 106 CAR+ cells/kg | CR: 8/9 (all MRD− in all) |
| Institution . | Gene transfer method . | ScFv* . | Costimulatory domain . | Patient populations . | Lymphodepleting chemotherapy . | Infused cell doses . | Responses observed . |
|---|---|---|---|---|---|---|---|
| CHOP3,4 | Lentivirus | FMC63 | 4-1BB | Pediatric ALL; n = 534 | Investigator’s choice | 1.07 × 106 to 17.36 × 106 CAR+ T cells/kg | CR: 50/53 (MRD− in 45/50) 12 mo RFS: 45% 12 mo OS: 78% |
| NCI5 | γ-retrovirus | FMC63 | CD28 | Pediatric ALL; n = 20 | Cy 900 mg/m2 ×1 + Flu 25 mg/m2 ×3 d | 1 × 106 (N = 16) vs 3 × 106 (N = 4) CAR+ T cells/kg | CR: 14/20 (MRD− in 12/14) LFS: 79% at 4.8 mo (MRD− CR patients) OS: 52% at 7.8 mo (all) |
| NCI6 | γ-retrovirus | FMC63 | CD28 | Adult CLL and B-NHL; n = 8 | Cy 60 mg/kg ×2 d + Flu 25 mg/m2 ×5 d | 0.3 × 107 to 3.0 × 107 CAR+ T cells/kg | ORR: 6/8 (CLL, 3/4; FL, 2/3); CR, n = 1 (CLL) and PR, n = 5 |
| NCI7 | γ-retrovirus | FMC63 | CD28 | Adult B-NHL; n = 15 | Cy 60 mg/kg ×1-2 d + Flu 25 mg/m2 ×5 d | 1 × 106 to 5 × 106 CAR+ T cells/kg | CR: 4/7 (refractory DLBCL), 4/6 (indolent B-NHL) |
| MSKCC8-10 | γ-retrovirus | SJ25C1 | CD28 | Adult ALL; n = 469 | Cy or Cy + Flu | 1 × 106 vs 3 × 106 CAR+ T cells/kg | CR: 37/45 (MRD− in 30/36) among evaluable patients 6 mo OS: 65% (all) and 80% (MRD− CR patients) |
| FHCRC11 | Lentivirus | FMC63 | 4-1BB | Adult ALL; n = 29 | Cy or Cy 60 mg/kg ×1 + Flu 25 mg/m2 ×3 d | 2 × 105, 2 × 106, and 2 × 107 CAR+ T cells/kg; 1:1 CD4+:CD8+ | CR: 10/12 (Cy only) and 14/14 (Cy + fludarabine); MRD status unspecified |
| FHCRC12 | Lentivirus | FMC63 | 4-1BB | Adult B-NHL; n = 28 Adult CLL; n = 6 | Cy 60 mg/kg ×1 ± etoposide or Cy 60 mg/kg ×1 + Flu 25 mg/m2 ×3 d | 2 × 105, 2 × 106, and 2 × 107 CAR+ T cells/kg 1:1 CD4+:CD8+ | ORR (B-NHL): 6/12 (CR, n = 1, PR, n = 5 in Cy cohort) and 8/12 (CR, n = 5, PR, n = 3 in Cy + Flu cohort) ORR (CLL): 5/6 (CR, n = 3, PR, n = 2) |
| UPenn13 | Lentivirus | FMC63 | 4-1BB | Adult CLL; n = 14 | Investigator’s choice | 0.14 × 108 to 11 × 108 CAR+ T cells | ORR: 8/14 (MRD− CR, n = 4, PR, n = 4) Median PFS: 7 mo Median OS: 29 mo |
| UPenn14 | Lentivirus | FMC63 | 4-1BB | Adult CLL; n = 26 | Investigator’s choice | 5 × 107 vs 5 × 108 CAR+ T cells | ORR: 9/23 (CR, n = 5, PR, n = 4) |
| UPenn15 | Lentivirus | FMC63 | 4-1BB | Adult B-NHL; n = 24† | Investigator’s choice | 3.08 × 106 to 8.87 × 106 CAR+ cells/kg | ORR: 15/22 (DLBCL, 7/13; FL, 7/7, MCL, 1/2) PFS: 62% at 11.7 mo |
| UPenn14 | Lentivirus | FMC63 | 4-1BB | Adult ALL; n = 12 | Investigator’s choice | 6.5 × 106 to 8.45 × 106 CAR+ cells/kg | CR: 8/9 (all MRD− in all) |
CHOP, Children’s Hospital of Philadelphia; CR, complete response; Cy, cyclophosphamide; DLBCL, diffuse large B-cell lymphoma; FHCRC, Fred Hutchinson Cancer Research Center; FL, follicular lymphoma; Flu, fludarabine; LFS, leukemia-free survival; MCL, mantle cell lymphoma; MRD−, minimal residual disease negative; MSKCC, Memorial Sloan Kettering Cancer Center; NCI, National Cancer Institute; ORR, objective response rate (in evaluable patients); OS, overall survival; PFS, progression-free survival; PR, partial response; RFS, relapse-free survival; UPenn, University of Pennsylvania.
ScFv from which CAR antigen-recognition moiety was derived.
Of 38 enrolled, 24 received the protocol-specified dose and were included in the analysis.