Clinical trials of CAR T-cell and bispecific antibodies therapies in the third-line setting for aggressive LBCL
| Clinical trial . | Construct . | Patients . | Histologies . | Response rates . | Survival outcomes . | Longest median follow-up . | Duration of response . | Rates of CRS . | Rates of neurotoxicity . | Treatment-related mortality . | FDA approved . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| CAR-T therapies for third-line LBCL | |||||||||||
| ZUMA-11,5 | Axi-cel | 101 | DLBCL, PMBCL, tFL | ORR 82% (CR 54%) | mPFS 5.9 mo 12 mo: PFS 44%, OS 59% 5 y: PFS 32%, OS 43% | 63.1 mo | mDOR 11.1 mo mDOCR 62.2 mo | 93% (13% grade 3+) | 64% (28% grade 3+) | 3 patients (3%), 1 death due to CRS, 1 death due to HLH | Yes |
| JULIET2,6 | tisa-cel | 115 | DLBCL, tFL, HGBL | ORR 53% (CR 39%) | mPFS 2.9 mo 12 mo: RFS 65%, OS 49% 40 mo: PFS 38%, OS 39% 5 y: PFS 31% | 60.7 mo | mDOR NR | 58% (22% grade 3+) | 21% (12% grade 3+) | 0 patients | Yes |
| TRANSCEND7 | Liso-cel | 256 | DLBCL, tFL, HGBL, PMBCL, FL 3B | ORR 73% (CR 53%) | mPFS 6.8 mo 1 y: PFS 44%, OS 58% | 18.8 mo | mDOR 17 mo | 42% (2% grade 3+) | 30% (10% grade 3+) | 7 patients (3%) | Yes |
| Bispecific antibody therapies for third-line LBCL | |||||||||||
| NCT030756968,9 | Glofitamab | 154 51 (33%) with prior CAR-T exposure | DLBCL, tFL, HGBL, PMBCL | ORR 52% (CR 39%) Prior CAR-T: CR 35% | mPFS 4.9 mo 1 y: PFS 37%, OS 50% | 12.6 mo | mDOR 18.4 mo mDOCR NR (74% remained in CR at median of 18.1 mo of follow-up) | 63% (4% grade 3+) | 8% (3% grade 3+) | 8 patients (5%) | Yes (June 2023) for LBCL after at least 2 lines of therapy |
| EPCORE NHL-1 (NCT03625037)10,11 | Epcoritamab (dose escalation) | 68 46 with LBCL | Any relapsed or refractory CD20+ mature B-cell NHL | ORR 68% (CR 45%) for LBCL | mPFS for LBCL: 9.1 mo | 9.3 mo | 75% of LBCL responders in ongoing remission at 6 mo | 59% (no grade 3+) | 6% (3% grade 3+) | 0 patients | Yes (May 2023) for LBCL after at least 2 lines of therapy |
| Epcoritamab (dose expansion) | 157 61 (39%) with prior CAR-T exposure | DLBCL, PMBCL, HGBL, FL 3B | ORR 63% (CR 39%) Prior CAR-T: ORR 54% (CR 34%) | mPFS 4.4 mo 6 mo: PFS 44% mPFS NR among patients with CR | 10.7 mo | mDOR 12 mo (9.7 mo if prior CAR-T) mDOCR NR (NR if prior CAR-T) | 50% (2.5% grade 3+) | 6% (0.6% grade 3+) | 9 patients (6%), 1 death due to ICANS | ||
| NCT0250040712,13 | Mosunetuzumab (phase I data) | 197 129 with aggressive NHL | Any relapsed or refractory B-cell NHL | ORR 35% (CR 19%) | mPFS 1.4 mo | 11.9 mo | mDOR 7.6 mo mDOCR 23 mo | 27% (1% grade 3+) | 10-18% (4% grade 3+) | 3 patients (1.5%) | Yes, for relapsed or refractory FL |
| Mosunetuzumab (phase II data) | 88 | DLBCL, tFL, HGBL | ORR 42% (CR 24%) Prior CAR-T: ORR 23% (CR 12%) | mPFS 3.2 mo mOS 11.5 mo Prior CAR-T: mPFS 1.4 mo | 10.1 mo | mDOR 7.0 mo mDOCR NR | 26% (2.3% grade 3+) | 1% (no grade 3+) | 3 patients (3.4%) | ||
| ELM-1 (NCT02290951)14 | Odronextamab | 85 with LBCL 33 (39%) of LBCL with prior CAR-T exposure | Any relapsed or refractory B-cell NHL | No prior CAR-T: ORR 53% (CR 53%) Prior CAR-T: ORR 33% (CR 27%) | No prior CAR-T: mPFS 11.5 mo Prior CAR-T: mPFS 2.0 mo | 4.2 mo | No prior CAR-T: mDOR NR Prior CAR-T: mDOR NR | 54% (7% grade 3+) | 12% (3% grade 3+) | 7 patients (5%) | No |
| Clinical trial . | Construct . | Patients . | Histologies . | Response rates . | Survival outcomes . | Longest median follow-up . | Duration of response . | Rates of CRS . | Rates of neurotoxicity . | Treatment-related mortality . | FDA approved . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| CAR-T therapies for third-line LBCL | |||||||||||
| ZUMA-11,5 | Axi-cel | 101 | DLBCL, PMBCL, tFL | ORR 82% (CR 54%) | mPFS 5.9 mo 12 mo: PFS 44%, OS 59% 5 y: PFS 32%, OS 43% | 63.1 mo | mDOR 11.1 mo mDOCR 62.2 mo | 93% (13% grade 3+) | 64% (28% grade 3+) | 3 patients (3%), 1 death due to CRS, 1 death due to HLH | Yes |
| JULIET2,6 | tisa-cel | 115 | DLBCL, tFL, HGBL | ORR 53% (CR 39%) | mPFS 2.9 mo 12 mo: RFS 65%, OS 49% 40 mo: PFS 38%, OS 39% 5 y: PFS 31% | 60.7 mo | mDOR NR | 58% (22% grade 3+) | 21% (12% grade 3+) | 0 patients | Yes |
| TRANSCEND7 | Liso-cel | 256 | DLBCL, tFL, HGBL, PMBCL, FL 3B | ORR 73% (CR 53%) | mPFS 6.8 mo 1 y: PFS 44%, OS 58% | 18.8 mo | mDOR 17 mo | 42% (2% grade 3+) | 30% (10% grade 3+) | 7 patients (3%) | Yes |
| Bispecific antibody therapies for third-line LBCL | |||||||||||
| NCT030756968,9 | Glofitamab | 154 51 (33%) with prior CAR-T exposure | DLBCL, tFL, HGBL, PMBCL | ORR 52% (CR 39%) Prior CAR-T: CR 35% | mPFS 4.9 mo 1 y: PFS 37%, OS 50% | 12.6 mo | mDOR 18.4 mo mDOCR NR (74% remained in CR at median of 18.1 mo of follow-up) | 63% (4% grade 3+) | 8% (3% grade 3+) | 8 patients (5%) | Yes (June 2023) for LBCL after at least 2 lines of therapy |
| EPCORE NHL-1 (NCT03625037)10,11 | Epcoritamab (dose escalation) | 68 46 with LBCL | Any relapsed or refractory CD20+ mature B-cell NHL | ORR 68% (CR 45%) for LBCL | mPFS for LBCL: 9.1 mo | 9.3 mo | 75% of LBCL responders in ongoing remission at 6 mo | 59% (no grade 3+) | 6% (3% grade 3+) | 0 patients | Yes (May 2023) for LBCL after at least 2 lines of therapy |
| Epcoritamab (dose expansion) | 157 61 (39%) with prior CAR-T exposure | DLBCL, PMBCL, HGBL, FL 3B | ORR 63% (CR 39%) Prior CAR-T: ORR 54% (CR 34%) | mPFS 4.4 mo 6 mo: PFS 44% mPFS NR among patients with CR | 10.7 mo | mDOR 12 mo (9.7 mo if prior CAR-T) mDOCR NR (NR if prior CAR-T) | 50% (2.5% grade 3+) | 6% (0.6% grade 3+) | 9 patients (6%), 1 death due to ICANS | ||
| NCT0250040712,13 | Mosunetuzumab (phase I data) | 197 129 with aggressive NHL | Any relapsed or refractory B-cell NHL | ORR 35% (CR 19%) | mPFS 1.4 mo | 11.9 mo | mDOR 7.6 mo mDOCR 23 mo | 27% (1% grade 3+) | 10-18% (4% grade 3+) | 3 patients (1.5%) | Yes, for relapsed or refractory FL |
| Mosunetuzumab (phase II data) | 88 | DLBCL, tFL, HGBL | ORR 42% (CR 24%) Prior CAR-T: ORR 23% (CR 12%) | mPFS 3.2 mo mOS 11.5 mo Prior CAR-T: mPFS 1.4 mo | 10.1 mo | mDOR 7.0 mo mDOCR NR | 26% (2.3% grade 3+) | 1% (no grade 3+) | 3 patients (3.4%) | ||
| ELM-1 (NCT02290951)14 | Odronextamab | 85 with LBCL 33 (39%) of LBCL with prior CAR-T exposure | Any relapsed or refractory B-cell NHL | No prior CAR-T: ORR 53% (CR 53%) Prior CAR-T: ORR 33% (CR 27%) | No prior CAR-T: mPFS 11.5 mo Prior CAR-T: mPFS 2.0 mo | 4.2 mo | No prior CAR-T: mDOR NR Prior CAR-T: mDOR NR | 54% (7% grade 3+) | 12% (3% grade 3+) | 7 patients (5%) | No |
FL 3B, grade 3B follicular lymphoma; HGBL, high-grade B-cell lymphoma; HLH, hemophagocytic lymphohistiocystosis; ICANS, immune effector cell-associated neurotoxicity syndrome; mDOCR, median duration of complete response; mDOR, median duration of response; mOS, median overall survival; mPFS, median progression-free survival; NR, not reached; PMBCL, primary mediastinal large B-cell lymphoma; tFL, transformed follicular lymphoma.