Introduction
B cell maturation antigen (BCMA)
Soluble BCMA (sBCMA)
BCMA-targeted immunotherapy
BCMA antibody-drug conjugate (ADC)
Name | Structure | Clinical trial information | Inclusion/exclusion criteria | Pt characteristics | Dosage | Major response | Most common AE |
---|---|---|---|---|---|---|---|
Belantamab mafodotin (GSK2857916) | Linker: non-cleavable MC Payload: MMAF | Phase 1 NCT02064387, DREAMM-1 | R/R MM received or were refractory to ASCT, alkylators, PI, and IMiD | 35 pts in dose expansion phase; median age 60; high-risk cytogenetics 13 (37%); 14 (40%) pts received > 5 prior lines; mDOF: 12.5 mo | 3.4 mg/kg every 3 wks | ORR 60%; sCR 2 (6%), CR 3 (9%), VGPR 14 (40%); mPFS 12 mo; mDOR 14.3 mo | G3+ thrombocytopenia (35%) anemia (17%); G1,2 corneal events: blurry vision (52%), dry eyes (37%), |
Phase 2 NCT03525678, DREAMM-2 [70] | R/R MM received or were refractory to ≥ 3 anti-MM therapies, including ASCT, alkylators, PI, IMiD, and CD38 mAb | 196 pts − 2.5 mg/kg cohort 97 pts; median age 65; high-risk cytogenetics 41 (42%); median prior therapies 7; mDOF 6.3 mo − 3.4 mg/kg cohort: 99 pts; median age 67; high-risk cytogenetics 47 (47%); median prior therapies 6; mDOF 6.9 mo | 2.5 or 3.4 mg/kg every 3 wks | − 2.5 mg/kg cohort: ORR 30 (31%); sCR/CR 3 (3%), VGPR 15 (15%); PD 56 (58%); mPFS 2.9 mo; − 3.4 mg/kg cohort: ORR 34 (34%); sCR/CR 3 (3%), VGPR 17 (17%); PD 55 (56%); mPFS 4.9 mo; | G3+ keratopathy (27% in the 2.5 mg/kg cohort and 21% in the 3.4 mg/kg cohort), thrombocytopenia (20% and 33%), and anemia (20% and 25%). TRD 2 | ||
MEDI2228 | Linker: protease-cleavable Payload: PBD | Phase 1 NCT03489525, | R/R MM received or were refractory to all standard therapy including PI, IMiD, and ASCT | – | – | – | – |
HDP-101 | Linker: non-cleavable MC Payload: Amanitin | Preclinical | – | – | – | – | – |
Belantamab mafodotin (GSK2857916; Blenrep; GlaxoSmithKline, GSK)
HDP-101
MEDI2228
BCMA-targeted CAR-T cells
Name | Manufacturer | BCMA scFv | Co-stimulatory | Transduction | Extra safety domain |
---|---|---|---|---|---|
CAR-BCMA | NCI | Murine | CD28 | γ-Retrovirus | No |
Idecabtagene vicleucel; Bb2121 | Bluebird Bio and Celgene | Murine | 4-1BB | Lentivirus | No |
Bb21217 | Bluebird Bio and Celgene | Murine | 4-1BB | Lentivirus | Yes, PI3K inhibitor |
LCAR-B38M | Nanjing Legend/Genscript Biotech | Bi-epitope | 4-1BB | Lentivirus | No |
JNJ-4528 | Janssen Research & Development | Bi-epitope | 4-1BB | Lentivirus | No |
CT053 | CARsgen Therapeutics | Fully human | 4-1BB | Lentivirus | No |
P-BCMA-101 | Poseida Therapeutics | Fully human anti-BCMA CentyrinTM | 4-1BB | PiggyBac™ (PB) DNA Modification System | No |
CART-BCMA | UPenn/Novartis | Fully human | 4-1BB | Lentivirus | No |
CT103A | Nanjing laso Biotherapeutics | Fully human | 4-1BB | Lentivirus | No |
JCARH125 | Juno Therapeutics | Fully human | 4-1BB | Lentivirus | No |
MCARH171 | MSKCC | Fully human | 4-1BB | γ-Retrovirus | Yes, tEGFR |
BCMA CAR-T | HRAIN Biotech | Fully human | 4-1BB | γ-Retrovirus | Yes, tEGFR |
KITE-585 | Kite, Gilead company | Fully human | CD28 | Lentivirus | No |
Name | Clinical trial information | Inclusion/exclusion criteria | Pt characteristics | Pre-condition | Dosage | Pharmacokinetics | Major response | Most common AE |
---|---|---|---|---|---|---|---|---|
Idecabtagene vicleucel; Bb2121 | Phase 1b NCT02658929 [71] | R/R MM who received or were refractory to ≥ 3 prior lines, including PI, IMiD | 33 pts (21 in dose-escalation; 12 in dose expansion); median age 60; median prior lines 7; high-risk cytogenetics 13 (45%); mDOF 11.3 mo | CTX + FAMP | 150 or 450 × 106 cells/pt | Expansion at all dose level, persist up to 1 yr | ORR 85%; CR 15 (45%); mPFS 11.8 mo | G3+ neutropenia (85%), leukopenia (58%), thrombocytopenia (45%), anemia (45%); CRS 23 (70%) G1–2, 2 (6%) G3+; NTX 14 (42%) G1–2, 13 (39%) G3+ |
Phase 2 NCT0336174 [103] | R/R MM who received or were refractory to ≥ 3 prior lines, including PI, IMiD, and CD38 mAb | 128 pts (54 received 450 × 106 cells); median age 61; median prior lines 6; triple-refractory 108 (84%); penta-refractory 33 (26%); mDOF 11.3 mo | CTX + FAMP | 150–450 × 106 cells/pt | Peak on d11, detectable in 29/49 (59%) pts at 6 mo and 4/11 (36%) pts at 12 mo | ORR 73.4%; CR 31.3%; mPFS 11.3 mo 450 × 106 cells dose cohort: ORR 81.5%; CR 35.2%; mPFS 11.3 mo | All grades cytopenia (94%); CRS 107 (83.6%) G1–2, 7 (5.5%) G3+; NTX 19 (14.9%) G1–2, 4 (3.1%) G3+ | |
Bb21217 | Phase 1 NCT03274219 [104] | R/R MM who received or were refractory to ≥ 3 prior lines, including PI, IMiD; ≥ 50% cell-surface BCMA expression | 22 pts; median age 63; median prior lines 7; ASCT 18 (82%); high-risk cytogenetics 7 (32%); mDOF 23 wk | CTX + FAMP | 150 or 350 or 450 × 106 cells/pt | 6/8 detectable at 6 mo, 2/2 detectable at 12 mo | ORR 83%; PD 6 | CRS 7 G1–2, 1 G3+; NTX 3 G1–2, 2 G3+ |
LCAR-B38M | Phase 1/2 NCT03090659 [105] | R/R MM who received or were refractory to ≥ 1 prior lines | 57 pts; median age 54 median prior lines 3; ASCT 10 (18%); mDOF 19 mo | CTX | Avg 0.5 × 106 cells/kg 3 split infusions | Detectable till 4 mo, at most 10 mo | ORR 88%; CR 42 (74%), VGPR 2 (4%), PR 6 (11%); mPFS 20 mo; 18-mo PFS 50%; 18-mo OS 68% | G3+ leukopenia (30%), thrombocytopenia (23%), increased AST (21%); CRS 46 (82%) G1–2, 4 (7%) G3+; NTX 1 (2%) G1–2 |
Phase 1/2 NCT03090659 [106] | R/R MM who received or were refractory to ≥ 3 prior lines, | 17 pts; median age 55 median prior lines 5; ASCT 8 (47%); mDOF 22 mo | CTX ± FAMP | Avg 0.7 × 106 cells/kg 1 infusion or 3 split infusions | Peak on d6–30, detectable till up to 9 mo | ORR 88%; CR 14 (82%), VGPR 1 (4%); mPFS 12 mo; 1-yr PFS 52.9%; 1-yr OS 82.3% | G3+ cytopenia 10 (59%); G3+ liver toxicity 5 (29%); CRS 10 (59%) G1–2, 7 (41%) G3+; NTX 0 | |
JNJ-4528 | Phase 1b/2 NCT03548207 [107] | R/R MM who received or were refractory to ≥ 3 prior lines, including PI, IMiD, CD38 mAb | 29 pts; median age 61; median prior lines 5; 76% penta-exposed, 86% triple-refractory, 31% penta-refractory; mDOF 9 mo | CTX + FAMP | Avg 0.75 × 106 cells/kg | Peak on d10-14, detectable till 6 mo, memory CD8+ CAR-T | ORR 100%; sCR 22 (76%), VGPR 6 (21%), PR 1 (3%); 6-mo PFS 93%; best mPFS 15 mo | G3+ neutropenia (100%), thrombocytopenia (69%), leukopenia (59%); CRS 27 (93%) G1–2, 2 (9%) G3+; NTX 3 G1–2, 1 G3+; DLT 1; TRD 1 |
CT053 | Phase 1 NCT03716856 [108] | R/R MM who received or were refractory to ≥ 2 prior lines | 24 pts; median age 60 median prior lines 4.5 high-risk cytogenetics 9 (38%); mDOF 333 d | CTX + FAMP | 1.5 × 108 cells/pt | Peak on d7–21, detectable till 172d, at most 341d | ORR 87.5%; sCR 14 (71%), CR 5 (21%), VGPR 1 (4%); mPFS 281 d; PD 9 | G3+ leukopenia (87.5%), neutropenia (66.7%), lymphopenia (79.2%), thrombocytopenia (25%); CRS 15 (62.5%) G1–2; NTX 2 (8%) G1–2, 1 (4%) G3+ |
P-BCMA-101 | Phase 2 NCT03288493 [109] | R/R MM who received or were refractory to ≥ 3 prior lines, including PI, IMiD, CD38 mAb | 12 pts; prior lines 3–9 mDOF 3 wk | CTX + FAMP | 0.75–15 × 106 cells/kg | Peak at 2–3 wks, remain detectable at 3 mo | 6 pts in higher dose cohort: ORR 83%; 1 sCR 1 VGPR 3 PR | G3+ cytopenia and febrile neutropenia; CRS 1 (8%) G1–2; NTX 0 |
CART-BCMA | Phase 1b NCT02546167 [110] | R/R MM who received or were refractory to ≥ 3 prior lines, including PI, IMiD, | 25 pts; median age 58; median prior lines 7; high-risk cytogenetics 24 (94%); ASCT 23 (92%); panta-refractory 11 (44%); mDOF 24 mo | None or CTX | 1–5 × 107 or 1–5 × 108 cells/pt | Peak on d10–14, remain detectable at 6 mo | ORR 48%; CR 2 (8%), VGPR 5 (20%), PR 5 (20%); best mPFS 125 d; PD 22 | G3+ leukopenia (44%), neutropenia (44%), lymphopenia (36%); CRS 14 (56%) G1–2, 8 (32%) G3+; NTX 5 (20%) G1–2, 3 (12%) G3+ |
CT103A | Phase 1 ChiCTR 1800018137 [111] | R/R MM who received or were refractory to ≥ 3 prior lines, including PI, IMiD, | 16 pts; median prior lines 4; mDOF 195 d | CTX + FAMP | 1–8 × 106 cells/kg | Peak at 2 wks, remain detectable at 6 mo | ORR 100%; CR/sCR 12 (75%), VGPR 2 (12.5%) | CRS 15 (94%) G1–2, 1 (6%) G3+; NTX 0; DLT 1; TRD 1 |
JCARH125 | Phase 1/2 NCT03430011 [112] | R/R MM who received or were refractory to ≥ 3 prior lines, including PI, IMiD, CD38 mAb, ASCT | 8 pts; median age 53; median prior lines 10; ASCT 8 (88%); panta-refractory 4 (50%); mDOF 5 wk | CTX + FAMP | 50 or 150 × 106 cells/pt | – | ORR 100%; sCR/CR 3 (37.5%), VGPR 2 (25%), PR 2 (25%); PD 0 | CRS 6 (75%) G1–2; NTX 2 (25%) G1–2, 1 (12.5%) G3+ |
MCARH171 | Phase 1 NCT03070327 [113] | R/R MM who received or were refractory to ≥ 2 prior lines, including PI, IMiD | 11 pts; median prior lines 6 | CTX + FAMP | 72, 137, 475, 818 × 106 cells/pt 1 to 2 doses | Peak expansion found in dose cohort 475, 818 × 106 | ORR 64%; mDOR 106 d | CRS 4 (40%) G1–2, 2 (20%) G3+; NTX 1 (9%) G1–2 |
BCMA CAR-T | Phase 1 NCT03093168 [114] | R/R MM who received or were refractory to ≥ 2 prior lines, including PI, IMiD; ≥ 5% cell-surface BCMA | 44 pts median prior lines ≥ 2 mDOF ≥ 1 mo | CTX + FAMP | 9 × 106 cells/kg | Expansion and persistence throughout the DOF | ORR 79.6%; sCR 2 (4.5%), CR 16 (36%), VGPR 8 (18%), PR 8 (18%); mPFS 15 mo; 2-yr PFS 49.16%; 2-yr OS 53.95% | CRS 10 (22.7%) G1–2, 3 (6.8%) G3+ |
CAR-BCMA
Idecabtagene vicleucel (ide-cel; bb2121) and bb21217
LCAR-B38M (JNJ-4528)
CT053
P-BCMA-101
CART-BCMA
CT103A
JCARH125
MCARH171
BCMA CAR-T cells with tEGFR
KITE-585
Bispecific CAR-T cells
CD19/BCMA bispecific CAR-T cells
BM38: CD38/BCMA bispecific CAR-T cells
CAR-NK cells targeting BCMA
Bispecific T cell engager (BiTE) and trispecific T cell engager (TiTE)
Name (manufacturer) | Structure | Clinical trial information | Inclusion/exclusion criteria | Pt characteristics | Dosage | Major Response | Most common AE |
---|---|---|---|---|---|---|---|
AMG 420 (Amgen) | BCMA/CD3 | Phase 1 NCT02514239 [72] | R/R MM who received or were refractory to ≥ 2 prior lines, including PI and IMiD; PC leukemia, extra-medullary relapse, CNS involvement, or prior ASCT were excluded | 42 pts; median age 65; median prior lines 4 | 0.2–800 μg/d, 4 wks infusion +2 wks off, for up to 5 cycles. Avg 2.5 ± 2.6 cycles | ORR 31%; sCR 14%, CR 7%, VGPR 4.8%, PR 4.8% | G3+ infection 12 (28.5%), polyneuropathy 2 (4.8%); G2–3 CRS 3 (7%); DLT 3 (7%) |
CC-93269 (Celgene) | BCMA (bivalent)/CD3 (monovalent) | Phase 1 NCT03486067 [167] | R/R MM who received or were refractory to ≥ 3 prior lines; hx of BCMA-directed therapy were excluded | 19 pts; median age 64; median prior lines 6; ASCT 16 (84%); all pts refractory to the last line | 0.15–10 mg/d for a 28-day cycle (D1, 8, 15, and 22 for Cycles 1–3; D1 and 15 for Cycles 4–6; and on D1 for Cycle 7). Median 4 cycles; Median DOT 14.6 wks | 12 pts w/ dose of ≥ 6 mg; ORR 10 (83.3%); sCR/CR 4 (33.3%), VGPR 7 (58.3%) | G3+ neutropenia (52.6%), anemia (42.1%), infections (26.3%), thrombocytopenia (21.1%); G1–2 CRS 17 (89.5%) |
PF-06863135 (Pfizer) | BCMA/CD3, IgG2a backbone | Phase 1 NCT03269136 [168] | R/R MM who received or were refractory to ≥ 3 prior lines, including PI, IMiD, CD38 mAb | 17 pts; median age 61; median prior lines 11; 5 pts (29%) had prior BCMA-targeted therapy | Once weekly non-continuous infusion in 6 dose-escalation groups | Minimal response 1 (6%); SD 6 (35%); PD 9 (53%) | G3+ thrombocytopenia (24%), anemia (18%); G1–2 CRS (24%) |
REGN5458 (Regeneron) | BCMA/CD3 | Phase 1 NCT03761108 [169] | R/R MM who received or were refractory to ≥3 prior lines, including PI, IMiD, CD38 mAb | 7 pts | 6 mg/kg, 16 weekly doses + maintenance 12 doses per 2 wks | ORR 4 (53.3%) | G1–2 CRS 3 (42.9%) |
AMG 701 (Amgen) | BCMA/CD3, extended half-life | Phase 1 NCT03287908 | R/R MM who received or were refractory to ≥ 3 prior lines, including PI, IMiD, CD38 mAb | – | – | – | – |
TNB383B (TeneoBio) | BCMA (high affinity)/CD3 (low affinity), IgG4 backbone | Phase 1 NCT03933735 | R/R MM who received or were refractory to ≥ 3 prior lines, including PI, IMiD, CD38 mAb | – | – | – | – |