Table 3 CAR-T studies with dual BCMA targets or non-BCMA targets.
From: CAR-T cell therapy in Multiple Myeloma: current status and future challenges
Study | Target antigen(s) | CAR-T | Study design | Patients | Outcomes |
|---|---|---|---|---|---|
NCT02135406 Phase 1 | CD19 | CTL019 (Tisa-cel, Kymriah, Novartis) CD19 scFv (FMC63) 4-1BB co-stimulatory domain Lentiviral vector | Salvage melphalan ASCT followed by 1.1-6 × 108 CTL019 CAR-T | N = 10 median 6 prior lines, 100% previous ASCT | ≥PR 80% at D100 20% had longer PFS after ASCT/CTL019 than initial ASCT CRS 10% (grade 1) |
ChicTR-01C-17011272 Phase 2 | BCMA/CD19 | Humanized CD19 scFv 4-1BB co-stimulatory domain Lentiviral vector BCMA scFv 4-1BB co-stimulatory domain Lentiviral vector | Fludarabine 30 mg/m2 for 3 days, cyclophosphamide 750 mg/m2 for 1 day 1 ×106 each CAR-T product | N = 62 RRMM | ORR 92%, ≥CR 60%, MRD negative 77%, median DOR 20.3 months, median PFS 18.3 months CRS 95% (Grade 3 10%), 11% neurotoxicity (≥ Grade 3 3%) |
NCT04935580 Phase 1/2 | BCMA/CD19 | GC012F CAR-T FasT CAR-T Platform | Standard lymphodepleting chemotherapy following induction chemotherapy 1-3 ×105 CAR-T cells | N = 22 High risk NDMM | ORR 100%, sCR 96%, 100% MRD negativity to 10-5 Median PFS not reached at 13.6 months CRS 27% (all Grade 1/2), no ICANS |
NCT04555551 Phase 1 | GPRC5D | MCARH109 GPRC5D scFv Lentiviral vector | Fludarabine 30 mg/m2, cyclophosphamide 300 mg/m2 days -5 to -3 25-450 ×106 CAR-T | N = 17 ≥ 3 Prior lines of therapy, including PI/IMiD/CD38 Median 6 prior lines, 100% penta-exposed, 94% triple class-refractory, 47% prior BCMA CAR-T | ORR 71% MTD identified at 150 ×106 CAR-T cells. Patients who received 25 – 150 ×106 CAR-T cells had CRS in 41% (all Grade 1/2) and no ICANS Grade 1 nail changes (65%), rash (18%) and dysgeusia (12%) |
NCT03287804 Phase 1/2 | BCMA/TACI | AUTO2 Truncated form of APRIL recognises BCMA and TACI OX40 co-stimulatory domain Gamma retroviral vector RQR8 safety switch | Fludarabine 30 mg/m2, cyclophosphamide 300 mg/m2 days -5 to -3 15-350 ×106 CAR-T | N = 11 ≥ 3 Prior lines of therapy Median 5 prior lines of therapy N = 7 received ≥225 × 106 CAR-T | At the higher dose levels, ORR 43%, PR 28%, VGPR 14% CRS 45% (all grade 1), no neurotoxicity |
NCT02203825 Phase 1 | NKG2D | Human NKG2D Gamma retroviral vector | No lymphodepletion 1 × 106- 3 × 107 CAR-T | N = 5 MM (n = 7 AML) 100% ≥5 prior lines of therapy | ORR 0% No CRS/ICANS/neurotoxicity |
NCT03464916 Phase 1 | CD38 | CAR2 Anti-CD38 A2 CAR-T | Dose escalation of CAR2 | RRMM previously treated with lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab | Not reported |
NCT03672318 Phase 1 | CD138 | ATLCAR Anti-CD138 CAR-T | Fludarabine 30 mg/m2, cyclophosphamide 300 mg/m2 days -5 to -3 1 × 106- 2 × 108 CAR-T | ≥ 3 Prior lines of therapy including PI/IMiD, or 2 prior lines if refractory to both | Not reported |
NCT03958656 Phase 1 CARAMBA | SLAMF7 | Sleeping Beauty gene transfer | Fludarabine 30 mg/m2, cyclophosphamide 300 mg/m2 days -5 to -3 Escalating doses | ≥ 3 Prior lines of therapy, Prior PI/IMiD | Not reported |
