Table 2.
Anti-BCMA CAR T-cell clinical trials in multiple myeloma (true to the time of writing).
| Trial number (name) | Site/ Sponsor | CAR | ScFV origin | Phase | n (at the time of reporting) | Antigen | Co-signaling domain/ CD3z | Design | Transfer method | Cell source | Conditioning | Dosage (CAR T cells/kg) | BCMA expression | Responses | Toxicity | Survival outcome | Additional info |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02215967 | NCI | CAR-BCMA | Murine | 1 | 16 | BCMA | CD28 | 2nd generation | Retroviral | Autologous | CP/Flu | 0.3–9.0 × 106 | >50% | ORR: 81%(2 sCR, 8 VGPR, 3 PR) | CRS: 15 (93.75%), including 2 Grade 4, 4 Grade 3, 7 Grade 2, and 2 Grade 1 | Median PFS: 7.2 months | Culture medium: anti-CD3 MoAb and IL2 |
| NCT03361748 (KarMMa) | Bluebird bio | bb2121/ Ide-cel | Murine | 1 | 128 | BCMA | 4-1BB | 2nd generation | Lentiviral | Autologous | CP/Flu | 150–450 × 106 | >50% |
ORR: 73% (33% CR) MRD (<10 − 5 nucleated cells): 26% |
1. CRS: 84%, 5% Grade ≥3 2. Neurotoxicity: 18%, 3% Grade ≥3 |
Median PFS: 8.8 months | Culture medium: anti-CD3/CD28, OKT3 |
|
(CRB-402) |
Bluebird Bio | bb21217 | Murine | 1 | 46 | BCMA | 4-1BB + PI3K inhibitor domain | 2nd generation | Lentiviral | Autologous | Flu/CP | 15, 30, 45 × 107 | >50% |
ORR: 24 (55%), 8 (18%) with ≥CR and 13 (30%) with VGPR Median DOR: 11.9 months |
1. CRS: 67%, including 14 Grade 1, 15 Grade 2, 1 Grade 3 and 1 Grade 5 2. 22% neurotoxicity, including 5 Grade 1, 2 Grade 2, 2 Grade 3, 1 Grade 4 |
NA |
1. Culture medium: additional PI3K inhibitor bb007 2. Enrichment for memory like T cells in bb21217 3. Presence of early memory-like T cells is associated with high peak expansion and prolonged response |
|
(LEGEND-2) |
Nanjing Legend Biotech Co | LCAR-B38M | Llama | 1/2 | 57 | Biepitope to BCMA (VHH1 and VHH2) | 4-1BB | 2nd generation | Lentiviral | Autologous | CP | 0.5–5 × 106 | Yes (cut-off not reported) |
ORR for EMD: 82.4% ORR for non-EMD: 90% |
1. CRS: 90%, Grade 1 (47%), Grade 2 (35%); Grade 3 (7%) 2. Neurotoxicity: 1 (Grade 1), dosed at 1.0 106 cells/kg |
Median follow up: 25 months Median PFS in EMD: 8.1 months Median PFS in non-EMD: 25 months |
Bispecific anti-BCMA variable fragments of llama heavy-chain antibodies |
| NCT03090660 | Nanjing Legend Biotech Co | LCAR-B38M | Murine | 1 | 17 | Biepitope to BCMA (VHH1 and VHH2) | 4-1BB | 2nd generation | Lentiviral | Autologous | CP | 0.21–1.52 × 106 | Yes (cut-off not reported) | ORR: 88.2% (13 sCR, 2 VGPR); | 1. CRS:100%, including 10 Grade 1/2, 6 Grade 3, and 1 Grade 5. 2. No neurotoxicity | 12-months PFS: 52.9% | Bispecific anti-BCMA variable fragments of llama heavy-chain antibodies |
|
(CARTITUDE-1) |
Johnson & Johnson | JNJ-4528/ cilta-cel | Llama | 1/2 | 25 | Biepitope to BCMA (VHH1 and VHH2) | 4-1BB | 2nd generation | Lentiviral | Autologous | NA | 0.75×106 | Yes |
ORR: 94.8% (sCR-55.7%, VGPR-32%, PR-7.2%) 6 months PFS: 87.4% 6 months OS: 93.8% |
CRS: 94.8%, (49.5% Grade 1, 39.2% Grade 2, 4.1% Grade 3, and 1% Grade 5) Neurotoxicity: 20.6% (10.3% Grade 3/4) |
NA |
1. CAR design takes after LCARB38M; Culture medium: IL-2 2. 67% patients had CAR T-cells below the level of quantification (2 cells/µL) in peripheral blood |
|
(EVOLVE) |
Juno Therapeutics, Inc | JCARH125 /Orva-cel | Human | 1/2 | 115 | BCMA | 4-1BB | 2nd generation | Lentiviral | Autologous | CP/Flu | 50, 150, 300, 450 and 600 × 106 | NA | ORR: 82% (27% CR) |
1. CRS: 75%, all Grade 1or 2 2. Neurotoxicity: 3 (2 Grade 1, 1 Grade 3) |
NA |
1. 1:1 CD4/CD8 ratio preselected prior to transduction and expansion. 2. Response did not correlate with baseline serum BCMA level 3. Serum BCMA declined with treatment, more so in responders. |
|
NCT03975907 (LUMMICAR-1) China |
CARsgen Therapeutics | CT053 | Human | 1 | 24 | BCMA | 4-1BB | 2nd generation | Lentiviral | Autologous | CP/Flu | 1.0-1.5×108 | Yes (no cut-off reported) |
ORR: 100% (4 sCR, 1 CR, 3 VGPR and 4 PR) All 5 subjects with CR/sCR were minimal residual disease (MRD)-negative at the 105 sensitivity level. |
CRS: 91.7%, (8 Grade 1 and 3 Grade 2) | NA | Peak expansion at 7–14 days after dosing in all subjects |
| NCT03915184 (LUMMICAR-2) North America | CARsgen Therapeutics | CT053 | Human | 1/2 | 20 enrolled, 14 received treatment | BCMA | 4-1BB | 2nd generation | Lentiviral | Autologous | CP/Flu |
8 patients received 1.5–1.8 × 108 6 patients received 2.5–3.0 × 108 |
Yes (no cut-off reported) |
ORR: 100% (2 sCR, 2 CR, 1 VGPR and 5 PR) 11 were MRD-negative at the 105 sensitivity level |
1. CRS: 86% Grade 1 or 2 2. Neurotoxicity: 1 subject Grade 2 |
NA | NA |
| NCT03070327 | Poseida Therapeutics, Inc | MCARH171 | Human | 1 | 11 | BCMA | 4-1BB + EGFRt | 2nd generation | Retroviral | Autologous | CP/Flu | 72–818 × 106 | >1% | 1. ORR:64% 2. 100% ORR observed in 5 patients received higher doses (450 × 106) | 1. CRS: 6 (60%), 4 grade 1–2, and 2 grade 3. 2. No grade 3 neurotoxicity | NA | No predefined CD4/CD8 ratio. Higher doses correlated with peak expansion and durability of response. |
| ChiCTR-OPC-16009113 | Huazong University | BCMA-CAR T cells | Murine | 1 | 28 | BCMA | CD28 | 2nd generation | Lentiviral | Autologous | CP/Flu | 5.4–25.0 × 106 | Yes (no cut-off reported) | Strong BCMA expression (n = 22): ORR, 87% (73% CR); Weak BCMA expression (n = 6): ORR, 100% (33% CR or VGPR) | 14% grade 3CRS. | Median DFS (strong vs weak): 296 vs 64 days | NA |
| NCT03661554 | ShenZhen Pregene Biotechnology Company, Ltd | BCMA-CAR T cells | Humanized alpaca | 1 | 16 | BCMA | 4-1BB | 2nd generation | Lentiviral | Autologous | CP/Flu | 2–10 × 106 | Yes (no cut-off reported) |
8 ORR: 84.6% (28 days, 13 patients) ORR: 100% (3sCR/CR, 1 VGPR, 3 PR) (10 weeks, 7 patients) |
2 patients with grade 3–4 CRS (0–2 in other patients) |
NA | NA |
| NCT02546167 | University of Pennsylvania–Novartis Alliance | CART-BCMA | Human | 1 | 25 | BCMA | 4-1BB | 2nd generation | Lentiviral | Autologous | With or without lymphdepletion |
Cohort 1: 1–5 × 108 CART-BCMA cells Cohort 2: CP 1.5 g/m2 + 1–5 × 107 CART-BCMA cells Cohort 3: CP 1.5 g/m2 + 1–5 × 108 CART-BCMA cells |
Not required |
ORR: 48% (CR- 8%) Cohort 3: ORR, 64%; CR: 9% |
1. CRS: 22 (88%); 8 grade 3–4 (all 1–5 108 dose) 2. Neurotoxicity (n = 8, 32%): 5 grade 1–2, 3 grade 3–4 |
Median PFS: Cohort 1- 2.2 months, Cohort 2- 1.9 months, Cohort 3- 4.2 months OS: 502 days |
BCMA intensity did not predict response. Responses correlated with CAR T-cell expansion with higher proportion of naive/memory phenotype cells. BCMA declined with treatment, more so in responders. |
| NCT03093168 | Henan University (HRAIN) | Anti-BCMA CAR | Human | 1 | 46 | BCMA | 4-1BB + EGFRt | 2nd generation | Retroviral | Autologous | CP/Flu | 9 × 106 | >5% |
ORR: 79.6% (2sCRs, 16CRs, 8VGPRs and 8PRs) MRD negativity: 16 patients |
CRS: 22.7% Grade 1-2, 6.8% Grade 3 CRS. No grade 4 CRS reactions developed and all toxicities were fully reversible. Neurotoxicity: 1(7%) |
Median PFS: 15 months 24-months PFS: 49.16% 24-months OS: 53.95% |
NA |
| NCT03338972 | Fred Hutchinson Cancer Research Center | FCARH143 | Human | 1 | 11 | BCMA | 4-1BB + EGFRt | 2nd generation | Lentiviral | Autologous | CP/Flu | 5 and 15 × 107 | >5% | ORR: 100% (sCR/CR: 55%, VGPR: 36%, PR: 9%) |
1. CRS: 91% (Grade 1 and 2) 2. Neurotoxicity: 9% |
NA | Infusion of 1:1 CD4/CD8 CAR-T ratio. BCMA antigen loss seen in 1 patient at time. CAR T cells remained detectable 90 days post infusion, representing ≤41.5% of CD3 + lymphocytes of relapse. |
| NCT03288493 | Poseida Therapeutics, Inc. | P-BCMA-101 (CARTyrin) | Human | 1, 3 + 3 | 43 | BCMA | 4-1BB + safety switch | 2nd generation | Piggyback-transposon | Autologous | CP/Flu | 0.75–15 × 106 | Not required | ORR: 100% (single CAR T agent or in combination with rituximab and lenalidomide) |
1. CRS:17% (1 Grade 3) 2. Neurotoxicity: 1 Grade 2 |
NA |
1. Nonviral PiggyBac DNA-delivery system: increases memory stem cells to increase persistence. It has a proprietary safety switch. Peak expansion was delayed/slower (14–21 days) 2. Addition of rituximab or lenalidomide pre- and post- lymphodepletion to prevent anti-CAR antibody development and increase T cell robustness, respectively |
| NCT03602612 | National Cancer Institute (NCI) | FHVH33 | Human | 1 | 15 | BCMA | 4-1BB | 2nd generation | Retroviral | Autologous | CP/Flu | 0.75 and 12.0 × 106 | Yes |
sCR/CR (20%) VGPR (7%) PR (53%) |
1. CRS Grade 1–2 (87%), Grade≥ 3 (7%) 2.Neurotoxicity (27%) |
NA | NA |
| NCT03549442 | Abramson Cancer Center | CAR-T-BCMA (Upenn) + CTL119 (humanized tisagenlecleucel) | Human | 1 | A = 6; B = 4 | CD19 + BCMA | 4-1BB | 2nd generation | Lentiviral | Autologous | CP/Flu | 5 × 108 total CAR-T | Yes (cut-off not reported) | ORR: 80% (1CR, 4VGPR, 3PR) | CRS:80%, all grade1-2 | NA | NA |
| NCT03455972 | The First Affiliated Hospital of Soochow University | CART-19/BCMA (cocktail) | NA | 1/2 | 9 | CD19 + BCMA | OX40/CD28 + EGFRt | 3rd generation | Lentiviral | Autologous | NA | 1 × 107 (CAR-T-CD19); Split dose for CART-BCMA (40% d1, 60% d2) | All with BCMA > 50% without CD19 expression on PCs | ORR: 100% (3 CR, 6 VGPR) | 1. CRS: 100%, all Grade1–2; no serious neurotoxicity | NA | Culture medium: Anti-CD3 beads |
| NCT03778346 | The Sixth Affiliated Hospital of Wenzhou Medical University | NA | NA | 1 | 30 (estimated) | Integrin β7, BCMA, CS1, CD38 and CD13 (single or up to 10 combination) | NA + simultaneously expressing IL7 and CCL19 | 4th generation | NA | Autologous | NA | 106—107 Total CAR-T | NA | NA | NA | NA | NA |
| NCT03271632 | Shenzhen Geno-Immune Medical Institute | NA | NA | 1/2 | 20 (estimated) | BCMA, CD38, CD56, CD138 | NA | 4th generation | NA | Autologous | NA | NA | Yes (cut-off not reported) | NA | NA | NA | To investigate the persistence and function of CAR T cells in the body after CAR T-cell infusion |
| NCT03196414 | The First Affiliated Hospital of Soochow University | SZ-MM-CART01 | NA | 1 | 29 | BCMA, CD19, CD138 | OX40/CD28 | 3rd generation | Lentiviral | Auto/allo | CP/Flu | 20–82 × 106 total CAR-T | NA | ORR:100% (sCR/CR: 54%, VGPR: 4%, PR: 29%) |
1. CRS: 66% Grade 1 and 2, 34% ≥ Grade 3 2. Neurotoxicity: 3% |
NA | NA |
| NCT03287804 | Autolus Limited | AUTO2 | NA | 1/2 | 12 | Ligand based: APRIL (BCMA and TACI) | CD28/OX40 + RQR8 safety switch | 3rd generation | Retroviral | Autologous | CP/Flu | 15–900 × 106 | NA | ORR: 43% (28% PRs and 14% VGPRs) | 45% CRS, all grade 1, no neurotoxocity | NA | Preliminary efficacy seen to date following treatment has been determined not sufficient to warrant further development- trial is terminated |
| NCT03767751 | Chinese PLA General Hospital | NA | NA | 1/2 | 80 | Bispecific to CD38 + BCMA | NA | NA | NA | Autologous | NA | 1–5 × 106 | NA | NA | NA | NA | NA |
| NCT03473496 | Zhujiang Hospital | NA | NA | 1/2 | 50 | CD38, BCMA, CD138, CD56 (single or double combination) | NA | NA | NA | Autologous | NA | 106–107 | NA | NA | NA | NA | NA |
| NCT03271632 | Shenzhen Geno-Immune Medical Institute | NA | NA | 1/2 | 20 | CD38, BCMA, CD56 (single or multi) | NA | NA | NA | Autologous | NA | NA | NA | NA | NA | NA | NA |
| NCT03638206 | Shenzhen BinDeBio Ltd. | NA | NA | 1/2 | 73 | CD38, BCMA, NY-ESO-1 (single or multi) | NA | NA | NA | Autologous | CP/Flu | NA | Yes (no cut-off reported) | NA | NA | NA | If NY-ESO-1 is positive expression, positive HLA-A*0201 is required at the same time |
| NA | National Cancer Institute, Bethesda | FHVH33 | Human | 1 | 21 | BCMA | 4-1BB | 2nd generation | Retroviral | Autologous | CP/Flu | 0.75 × 106, 1.5 × 106, 3 × 106, 6 × 106 and 12 × 106 | NA | ORR: 90% (12 sCR, CR and VGPR) |
1. CRS: 95% (76% Grade 1 or 2, 19% Grade 3) 2. Neurotoxicity: 38% (23% Grade 1 or 2, 9% Grade 3, 4% Grade 4) |
NA | NA |
| NCT04236011 NCT04182581 | Shanghai Changzheng Hospital; Gracell Biotechnologies (Shanghai) Co., Ltd | GC012F | NA | Early 1 | 16 | BCMA and CD19 (manufactured with FasT CARplatform) | NA | NA | Lenviral | Autologous | CP/Flu |
Dose Level 1: 1 × 105/Kg (DL1) (1 patients) Dose Level 2: 2 × 105/Kg (DL2) (9 patients) Dose Level 3: 3 × 105/Kg (DL3) (6 patients) |
Clear expression by flow |
ORR: 93.8% (sCR/CR: 56.3%) MRD negative: 8.6% (11/14) at month 1, 100% at month 3 (11/11) and 100% at month 6 (10/10) |
CRS Grade 1–2: 87.5% CRS Grade 3: 12.5% |
NA | The CAR-T median proliferation peak was reached on Day10 (Day8–Day14) |
| NCT04155749 | Arcellx, Inc | ARC-101 | Synthetic (non-scFv) | 1 | 3 | BCMA | 4-1BB | 2nd generation | NA | Autologous | CP/Flu | 100, 300, and 900 × 106 cells | Not required | 1 sCR (MRD-10-4), 1 sCR, 1 sCR (MRD-10-6) |
1. CRS: 3 subjects 2. Neurotoxicity: 1 subject |
NA | Median drug product CAR T expression was 76% (min:max 72–78%) of total CD3 + T cells |
| NCT04322292 NCT03815383 NCT03751293 NCT04295018 | Institute of Hematology & Blood Diseases Hospital | C-CAR088 | Human | 1 | 21 | BCMA | 4-1BB | 2nd generation | Lenviral | Autologous | CP/Flu | 1.0 × 106 cells (n = 3), 3 × 106 cells (n = 11) and 4.5~6 × 106 cells (n = 7) | NA |
Best overall response included 6 complete responses (CRs), 10 very good partial responses (VGPRs) and 4 partial responses (PRs) In the 3 × 106 CAR-T cells/kg dose group, 5/11(45%) patients achieved CR |
CRS: 20 patients (95%) Grade 1–2, 1 patient Grade 3 | NA |
1. Cultured in serum-free, automated and digital, closed system 2. The median vein to vein time was 16 days 3. Median time to CRS was 6.5 days (range: 1–11 days) and median duration of CRS was 5 days (range: 2–10 days) |
| NCT04093596 (UNIVERSAL) | Allogene Therapeutics | ALLO-715 | NA | 1 | 19 (estimated) | BCMA | NA | NA | NA | Allogeneic | CP or Fu or ALLO-647 (anti-CD52 mAb, for selective and prolonged host lymphodepletion) | 40, 160, 320, and 480 × 106 | NA | ORR for DL3 (320 × 106 CAR T): 60% (1 sCR and 1 VGPR) | CRS: 4 pts (24%). Three episodes were Grade 1 and 1 was Grade 2; all resolved without tocilizumab or corticosteroids | NA | All responses were initially observed at day 14 |
| NCT04613557 (IMMUNICY-1) | Celyad Oncology SA | CYAD-211 | NA | 1 | 12 (estimated) | BCMA | NA | NA | NA | Allogeneic | CP/Flu | 30 to 300 × 106 cells | NA | NA | NA | NA | shRNA-based elimination of TCR |
| NCT03940833 | Asclepius Technology Company Group (Suzhou) Co., Ltd | BCMA CAR-NK 92 | Human | 1/2 | 20 (estimated) | BCMA (CAR NK) | NA | NA | NA | Allogeneic | NA | NA | NA | NA | NA | NA | NA |
| NCT04244656 | CRISPR Therapeutics AG | CTX-120 | NA | 1 | 80 (estimated) | BCMA | NA | NA | Ex vivo using CRISPR-Cas9 | Allogeneic | NA | NA | NA | NA | NA | NA | NA |
| NCT04171843 (PBCAR269A-01) | Precision BioSciences, Inc. | PBCAR269A | NA | 1/2a | 48 (estimated) | BCMA | NA | NA | NA | Allogeneic | CP/Flu | 0.6, 2, and 6 × 106 | NA | NA | NA | NA | Developed by using the unique ARCUS genome editing technology to modify the cells via a single-step engineering process. By inserting the CAR gene at the T-cell receptor (TCR) locus, this process knocks in the CAR while knocking out the TCR |
EMD Extra-medullary disease, MRD Minimal Residual Disease, DOR Duration of Response, CP Cyclophosphamide, Flu Fludarabine, CRS Cytokine Release Syndrome, PFS Progression-free survival, OS Overall Survival, ORR Overall Response Rate, sCR Stringent Complete Response, CR Complete Response, VGPR Very Good Partial Response, PR Partial Response.