Summary of clinical trials for CD19 CARTs and bispecific antibodies
| . | Axi-cel4,34 . | Tisa-cel6,7 . | Liso-cel8 . | Mosunetuzumab15 . | Epcoritamab16 . | Glofitamab17,18 . | Odronextamab19 . |
|---|---|---|---|---|---|---|---|
| Structure | CD19/CD3z/CD28 | CD19/CD3z/41BB | CD19/CD3z/41BB | Full-length humanized, IgG1 CD20/CD3 BsAb | CD20/CD3 BsAb | CD20/CD3 BsAb with 2:1 molecular configuration with bivalent binding to CD20 and monovalent binding to CD3 | Hinge-stabilized, fully human IgG4 CD20/CD3 BsAb |
| Route of administration | IV | IV | IV | IV or SC | SC | IV | IV |
| Trial/NCT | ZUMA-1 | JULIET | TRANSCEND | NCT02500407 | NCT03625037 | NCT03075696 | NCT02290951 |
| N = treated (aggressive histology) | 101 | 111 | 269 | 141 | 45 | 127 | 71 |
| Median lines prior therapy (range) | 3 (2-4) | Median not reported; range 1-6 | 3 (2-4) | 3 (1-14); 23 pts with prior CART | 3 (1-6); 6 pts with prior CART | 3 (1-13) | 3 (1-11); 29 pts with prior CART |
| Dosing | 2 × 106/kg × 1 dose | 0.6-6.0 × 108 × 1 dose | 0.5-1.0 × 108 × 1 dose | Step-up dosing on days 1, 8, and 15 of cycle 1, followed by fixed doses on day 1 of each 21-day cycle for up to 17 cycles | Flat dose in 28-day cycles (q1w: cycles 1–2; q2w: cycles 3–6; q4w thereafter) until disease progression or unacceptable toxicity | Step-up dosing on cycle (C) 1, day (D) 1 and 8 and then at the target dose from C2D1, q 3 weeks for up to 12 cycles | Step-up dose consisting of initial dose at week (W) 1, an intermediate dose at W2, and thereafter a fixed weekly dose until W12 followed by maintenance q2w |
| Median time to manufacture | Leukapheresis → infusion: 17 days | Enrollment → infusion: 21-day target | Leukapheresis → infusion: 24-day target | Immediate off-the-shelf immunotherapy | |||
| Median follow-up | 4 years | 40.3 months | 18.8 months | Not reported | 8.3 months | 13.5 months | 3.9 months |
| ORR (%) | 82 | 52 | 73 | 35 | 67 | 71 | • Without prior CART (n = 11): ORR 55% • Post-CART (n = 24): ORR 33% |
| CR (%) | 54 | 40 | 53 | 19 | 33 | 64 | • Without prior CART (n = 11): CR 55% • Post-CART (n = 24): CR 21% |
| Median DOR (mo) | 8.1 | Not reached | Not reached | Median time from first CR: 8.8 | Not yet mature | 5.5 | • Without prior CART: 10.3 • Post-CART: 2.8 |
| Median PFS (mo) | 5.8 | <6 months; not reached in CRs | 6.8 | Not yet mature | Not yet mature | 2.9 | Not yet mature |
| Median OS (mo) | 25.8 | 11.1 | 21.1 | Not yet mature | Not yet mature | Not yet mature | Not yet mature |
| CRS (%) | All grades: 93 ≥G3: 13 | All grades: 58 ≥G3: 22 | All grades: 42 ≥G3: 2 | All grades: 28 ≥G3: 1.4 | All grades: 58 ≥G3: 0 | All grades: 50 ≥G3: 3.5 | All grades: 62 ≥G3: 7 |
| ICANS (%) | All grades: 64 ≥G3: 28 | All grades: 21 ≥G3: 12 | All grades: 30 ≥G3:10 | All grades: 1.4 ≥G3: 0 | All grades: 6 ≥G3: 3 | All grades: 5.3 ≥G3: 0 | All grades: not reported ≥G3: 2.3 |
| Population applicability/considerations | DLBCL/PMBCL/TFL | DLBCL/TFL | DLBCL/PMBCL/transformation from indolent lymphoma; FL grade 3B; preferred for systemic + concurrent secondary CNS disease or post-alloSCT | Aggressive B-cell lymphoma prior to and post-CART | Aggressive B-cell lymphoma prior to and post-CART | Aggressive B-cell lymphoma | Aggressive B-cell lymphoma prior to and post-CART |
| . | Axi-cel4,34 . | Tisa-cel6,7 . | Liso-cel8 . | Mosunetuzumab15 . | Epcoritamab16 . | Glofitamab17,18 . | Odronextamab19 . |
|---|---|---|---|---|---|---|---|
| Structure | CD19/CD3z/CD28 | CD19/CD3z/41BB | CD19/CD3z/41BB | Full-length humanized, IgG1 CD20/CD3 BsAb | CD20/CD3 BsAb | CD20/CD3 BsAb with 2:1 molecular configuration with bivalent binding to CD20 and monovalent binding to CD3 | Hinge-stabilized, fully human IgG4 CD20/CD3 BsAb |
| Route of administration | IV | IV | IV | IV or SC | SC | IV | IV |
| Trial/NCT | ZUMA-1 | JULIET | TRANSCEND | NCT02500407 | NCT03625037 | NCT03075696 | NCT02290951 |
| N = treated (aggressive histology) | 101 | 111 | 269 | 141 | 45 | 127 | 71 |
| Median lines prior therapy (range) | 3 (2-4) | Median not reported; range 1-6 | 3 (2-4) | 3 (1-14); 23 pts with prior CART | 3 (1-6); 6 pts with prior CART | 3 (1-13) | 3 (1-11); 29 pts with prior CART |
| Dosing | 2 × 106/kg × 1 dose | 0.6-6.0 × 108 × 1 dose | 0.5-1.0 × 108 × 1 dose | Step-up dosing on days 1, 8, and 15 of cycle 1, followed by fixed doses on day 1 of each 21-day cycle for up to 17 cycles | Flat dose in 28-day cycles (q1w: cycles 1–2; q2w: cycles 3–6; q4w thereafter) until disease progression or unacceptable toxicity | Step-up dosing on cycle (C) 1, day (D) 1 and 8 and then at the target dose from C2D1, q 3 weeks for up to 12 cycles | Step-up dose consisting of initial dose at week (W) 1, an intermediate dose at W2, and thereafter a fixed weekly dose until W12 followed by maintenance q2w |
| Median time to manufacture | Leukapheresis → infusion: 17 days | Enrollment → infusion: 21-day target | Leukapheresis → infusion: 24-day target | Immediate off-the-shelf immunotherapy | |||
| Median follow-up | 4 years | 40.3 months | 18.8 months | Not reported | 8.3 months | 13.5 months | 3.9 months |
| ORR (%) | 82 | 52 | 73 | 35 | 67 | 71 | • Without prior CART (n = 11): ORR 55% • Post-CART (n = 24): ORR 33% |
| CR (%) | 54 | 40 | 53 | 19 | 33 | 64 | • Without prior CART (n = 11): CR 55% • Post-CART (n = 24): CR 21% |
| Median DOR (mo) | 8.1 | Not reached | Not reached | Median time from first CR: 8.8 | Not yet mature | 5.5 | • Without prior CART: 10.3 • Post-CART: 2.8 |
| Median PFS (mo) | 5.8 | <6 months; not reached in CRs | 6.8 | Not yet mature | Not yet mature | 2.9 | Not yet mature |
| Median OS (mo) | 25.8 | 11.1 | 21.1 | Not yet mature | Not yet mature | Not yet mature | Not yet mature |
| CRS (%) | All grades: 93 ≥G3: 13 | All grades: 58 ≥G3: 22 | All grades: 42 ≥G3: 2 | All grades: 28 ≥G3: 1.4 | All grades: 58 ≥G3: 0 | All grades: 50 ≥G3: 3.5 | All grades: 62 ≥G3: 7 |
| ICANS (%) | All grades: 64 ≥G3: 28 | All grades: 21 ≥G3: 12 | All grades: 30 ≥G3:10 | All grades: 1.4 ≥G3: 0 | All grades: 6 ≥G3: 3 | All grades: 5.3 ≥G3: 0 | All grades: not reported ≥G3: 2.3 |
| Population applicability/considerations | DLBCL/PMBCL/TFL | DLBCL/TFL | DLBCL/PMBCL/transformation from indolent lymphoma; FL grade 3B; preferred for systemic + concurrent secondary CNS disease or post-alloSCT | Aggressive B-cell lymphoma prior to and post-CART | Aggressive B-cell lymphoma prior to and post-CART | Aggressive B-cell lymphoma | Aggressive B-cell lymphoma prior to and post-CART |
alloSCT, allogeneic stem cell transplantation; DOR, duration of response; FL: follicular lymphoma; IgG: immunoglobulin G; PMBCL, primary mediastinal B-cell lymphoma; TFL, transformed follicular lymphoma; tisa-cel, tisagenlecleucel.