Skip to main content

Table 3 Interim results of clinical trials of BCMA-targeted CAR-T cell products

From: BCMA-targeted immunotherapy for multiple myeloma

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+
  1. Avg average, ASCT autologous or allogenic stem cell transplantation, CR complete response, CRS cytokine release syndrome, CTX cyclophosphamide, d day, DLT dose-limiting toxicity, FAMP fludarabine, G grade, IMiD immunomodulatory imide drugs, mDOF median duration of follow-up, mDOR median duration of response, mo month, mPFS median progression-free survival, NTX neurotoxicity, ORR overall response rate, OS overall survival, PD progressive disease, PI proteasome inhibitor, PR partial response, pt patient, sCR stringent complete response, TRD treatment-related death, VGPR very good partial response, wk week, yr year