Table 5 Results of clinical trials of CD19/CD22 dual-targeting CAR-T cells
Clinical trial information | Institution | Dual-targeting strategy | CAR structures | Disease and patients | Prior CD19 CAR-T treatment at baseline | ORR(≥ CR, best response) | Prognosis | CRS at any grade (grade ≥ 3), evaluation criteria | Neurotoxicity at any grade (grade ≥ 3), evaluation criteria |
|---|---|---|---|---|---|---|---|---|---|
Observational study ChiCTR-OPN-16008526 [86] | Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology | Sequential infusion without interval (D0-D3) | anti-CD19 scFv (Murine)/4-1BB anti-CD22 scFv (Murine)/4-1BB | R/R B-ALL 51 pts R/R B-cell NHL 38 pts | - | B-ALL: 98% (96%) in 50 evaluable pts B-cell NHL: 72.2% (50%) in 36 evaluable pts | B-ALL: mPFS 13.6 mos, mOS 31 mos B-cell NHL: mPFS 9.9 mos, mOS 18 mos | 95.5%(17.9%) Lee criteria | CRES 13.5% (1.1%) CTCTE criteria |
Observational study ChiCTR-ONC-17013648 [87] | Beijing Boren Hospital | Sequential infusion | FMC63 scFv/4-1BB anti-CD22 scFv (human)/4-1BB | R/R B-ALL 21 pts | 100% (16 CR, 3 PR, 2 relapsed) | 95% (95%) | 18-month OS rate 88.5% 18-month EFS rate 67.5% | 52% (0%) Penn criteria | 0% (0%) CTCTE criteria |
Phase 1 ChiCTR-OIB-17013670 [88] | Beijing Boren Hospital | Sequential infusion | anti-CD19 scFv/4-1BB anti-CD22 scFv/4-1BB | R/R B-ALL 20 pts | - | 100% (100%) | mLFS/mOS not reached 1-year LFS rate 79.5% 1-year OS rate 92.3% | CD19 CAR-T 90% (5%) CD22 CAR-T 75% (0%) | CD19 CAR-T 15% (5%) CD22 CAR-T 15% (0%) |
Phase 2 ChiCTR2000032211 [89] | Multicenter | Coadministration (1:1) | anti-CD19 scFv/4-1BB anti-CD22 scFv/4-1BB | B-ALL 6 pts R/R B-ALL 188 pts B-ALL with isolated EMD 31 pts | - | 99% (99%) | 12-month EFS rate 73.5% | 88% (28.4%) ASTCT criteria | 20.9% (4.0%) ASTCT criteria |
Phase 1 NCT03289455 [93] | Autolus PLC | Bicistronic CAR-T | FMC63 scFv/OX40 LT22 scFv-COMP/4-1BB | R/R B-ALL 15 pts | - | 86.7% ( 86.7%) | - | 80% (0%) Lee criteria | ICANS 26.7% (0%) ASTCT criteria |
Phase 1 (UCAR-T) NCT04227015 [95] | The First Affiliated Hospital, School of Medicine, Zhejiang University | Tantem CAR-T | FMC63 scFv-m971 scFv/4-1BB | R/R B-ALL 6 pts | - | 83.3% (83.3%) | - | 100% (16.7%) | 0% (0%) |
Phase 1 ChiCTR1800015575 [96] | The First Affiliated Hospital, School of Medicine, Zhejiang University | Tantem CAR-T | FMC63 scFv-anti-CD22 scFv(human)/4-1BB | R/R B-cell lymphoma 16 pts | - | 87.5% (62.5%) | 2-year OS rate 77.3% 2-year PFS rate 40.2% mPFS 246Â days | 100% (6.3%) ASTCT criteria | 0% (0%) CTCAE criteria |
Phase 1 NCT03185494 [97] | Institute of Basic Medicine, Chinese PLA General Hospital | Tantem CAR-T | m971 scFv-FMC63 scFv/4-1BB | R/R B-ALL 6 pts | - | 100% (100%) | - | 100% (0%) Lee criteria | ICANS 0% (0%) ASTCT criteria |
Phase 1 NCT03233854 [102] | Stanford University School of Medicine | Loop CAR-T | FMC63 VH-m971 VL-m971 VH-FMC63 VL/4-1BB | R/R B-ALL 17 pts R/R LBCL 21 pts | DLBCL 65% | B-ALL: 100% (80%) LBCL: 62% (29%) | - | 76% (5%) Lee criteria | 37% (10.5%) CTCAE criteria |
Phase 1 NCT03919526 [103] | Shanghai General Hospital, Shanghai Jiaotong University School of Medicine | Loop CAR-T | FMC63 VL-m971 VH-m971 VL-FMC63 VH/4-1BB | B-ALL 15 pts | - | 100% (100%) | mRFS/mOS not reached 12-month RFS rate 77% 12-month OS rate 86% | 26.7% (0%) ASTCT criteria | ICANS 0% (0%) ASTCT criteria |