Table 3 Interim results of clinical trials of CD22 CAR-T cells
Clinical trial information | Institution | Transduction/costimulatory domain/scFv (CAR-T product or manufacture procedure) | Disease and patients | Prior CD19 CAR-T | CD19 negative or dim | Dosage | Pharmacokinetics | ORR(≥ CR, best response) | Prognosis | CRS at any grade (grade ≥ 3), evaluation criteria | Neurotoxicity at any grade (grade ≥ 3), evaluation criteria |
|---|---|---|---|---|---|---|---|---|---|---|---|
Phase 1 NCT02315612 [20] | NCI | Lentivirus/4-1BB/m971 | R/R B-ALL 21 pts | 71.4% | 47.6% | 0.3 × 106 cells/kg 1 × 106 cells/kg 3 × 106 cells/kg | Peak on D14, persist up to 18 mos | 57% (57%) | - | 76% (0%) Lee criteria | 37.5% (0%) in first 16 patients |
Phase 1 NCT02315612 [24] | NCI | Lentivirus/4-1BB/m971 (CD4/CD8 TCS) | R/R B-ALL 57 pts R/R DLBCL 1 pt | 62% | 56.9% | 0.3 × 106 cells/kg 1 × 106 cells/kg 3 × 106 cells/kg | Peak on D14—D21, higher in those at CD4/CD8 TCS cohort | 71.9% (70.2%) in evaluable 57 pts | mRFS (CR) 6.0 mos mOS (CR) 13.4 mos | 86.2% (8.6%) Lee criteria | 32.8% (1.7%) ASTCT criteria |
Phase 1 ChiCTR-OIC-17013523 [21] | Beijing Boren Hospital | Lentivirus/4-1BB/- (YK-CD22BB-002) | R/R B-ALL 34 pts | 91% | 41.2% | 0.2 ~ 34.7 × 105 cells/kg | Peak on D12—D15 median persistence time was 28 days by FCM | 81.3% (78.1%) in 32 evaluable pts | - | 91.2% (2.9%) Lee criteria | 17.6% (0%) CTCAE criteria |
Phase 1 ChiCTR2000028793 [31] | Beijing Boren Hospital | Lentivirus/4-1BB/- (CD22-CARFH80) | R/R B-ALL 8 pediatric pts | 100% | 12.5% | 0.68 ~ 9.4 × 106 cells/kg | Peak on D11- D15 | 87.5% (75%) | - | 87.5% (12.5%) ASTCT criteria | ICANS 25% (12.5%) ASTCT criteria |
Two pilot studies NCT02650414 and NCT02588456 [81] | UPenn/Children’s Hospital of Philadelphia | Lentivirus/4-1BB/m971 (CART22) | R/R B-ALL 3 adult pts / 5 pediatric pts | 25% | 75% | 39.6 ~ 500 × 106 cells/pt | 2 CR pts showed significant CAR-T expansion within D20 | 50% (50%) | - | 75% (12.5%) Penn criteria | - |
Phase 1 PLAT-07(NCT04571138) [25] | Seattle Children's Hospital | - /4-1BB/m971 (SCRI-CAR22v2) | R/R B-ALL 3 pts | 100% | 66.7% | 2 × 105 cells/kg | - | 100% (100%) | - | - | - |
New Treatment Measure Clinical Study ChiCTR1800019298 [26] | Tianjin First Central Hospital | -/4-1BB/- | R/R B-ALL 6 pts R/R DLBCL 7 pts | 100% | 33.3% (B-ALL) | DLBCL: 2.11 ± 0.24 × 106 cells/kg B-ALL: 2.07 ± 0.42 × 106 cells/kg | Peak on D14 | DLBCL: 85.7% (57.1%) B-ALL: 33.3% (33.3%) | - | DLBCL: 42.9% (0%) B-ALL: 100% (16.7%) Lee criteria | ICANS 0% (0%) ASTCT criteria |
Phase 1 NCT04150497(BALLI-01) [27] | Cellectis S.A | Lentivirus/4-1BB/- (UCAR-T22, disruption of TRAC and CD52 genes using TALEN technology) | R/R B-ALL 3 pts | 33.3% | - |  ~ 1 × 106 cells/kg | Peak on D9—D14 | 66.7% (33.3%) | - | 33.3% (0%) | 0% (0%) |
Phase 1 NCT04088890 [28] | Stanford University School of Medicine | Lentivirus/4-1BB/m971 (CD4/CD8 T selection) | R/R LBCL 3 pts | 100% | 66.7% | 1 × 106 cells/kg | Peak on D14, persist up to 3 mos by qPCR | 100% (100%) | - | 100% (0%) ASTCT criteria | ICANS 0% (0%) ASTCT criteria |
Phase 1 NCT04088890 (cohort expansion) [29] | Stanford University School of Medicine | Lentivirus/4-1BB/m971 | R/R LBCL 21 pts | 95% | - | 1 × 106 cells/kg 3 × 106 cells/kg | Peak on D14 | 85.7% (66.7%) | mPFS not reached mOS not reached | 100% (4.8%) ASTCT criteria | ICANS 19% (0%) ASTCT criteria |
Phase 1 NCT02650414 [30] | UPenn | Lentivirus/4-1BB/m971 (CART22-65 s) | R/R B-ALL 17 pts | 94.1% | 100.0% | 0.8 ~ 10 × 106 cells/kg (3—day fractionated dosing) | Peak on D20 | 76.5% (76.5%) | mRFS 5.3 mos mEFS 5.8 mos mOS 16.5 mos | 88.2% (0%) | 35.3% (0%) |