Table 1.
Clinical trials with targeted BCR inhibition as single agent treatments.
| Targets | Drug/Regimen | Clinical Trial | Phase | Nb Pts | Status | Conditions | Response Data | References |
|---|---|---|---|---|---|---|---|---|
| BTK | Acalabrutinib | NCT02112526 | 1 | 21 | Active | R/R DLBCL | ORR 24%, CR 19% AEs Grade 3/4 44% |
[130] |
| BTK | DTRMWXHS-12 | NCT02891590 | 1 | 13 | Completed | R/R B-cell Lymphomas | Well-tolerated and no DLT achieved | [131] |
| BTK | Ibrutinib | NCT00849654 | 1 | 66 | Completed | B-cell Lymphomas | ORR 60% CR 16% PFS 13.6 months |
[132] |
| BTK | Ibrutinib | NCT01704963 | 1 | 15 | Completed | R/R B-cell Lymphomas | ORR 73.3% | [133] |
| BTK | Ibrutinib | NCT01325701 | 2 | 78 | Completed | R/R DLBCL | CR or PR in 37% (ABC) and in 5% (GCB) | [134] |
| BTK | Ibrutinib | NCT02207062 | 2 | 20 | Active | R/R B-cell Lymphomas | ORR 35% CR 15% PFS 4.1 months OS 22.8 months |
[135] |
| BTK | Ibrutinib | NCT01804686 | 3 | 700 | Active | CLL, SLL, MCL, FL DLBCL, WM | CR 27.6% PR 42.2% PFS 12.5 months |
[136] |
| BTK | TG1701 | NCT03664297 | 1 | 86 | Active | B-cell Lymphomas | NA | NA |
| BTK | Vecabrutinib | NCT03037645 | 1 & 2 | 39 | Terminated | CLL, SLL, MCL, WM, DLBCL, FL, MZL | Well tolerated but terminated due to insufficient evidence of activity | NA |
| BTK | Zanubrutinib | NCT03189524 | 1 | 44 | Completed | R/R MCL | CR 86.6% DOR 19.5 months PFS 22.1 months |
[129] |
| BTK | Zanubrutinib | NCT03145064 | 2 | 41 | Completed | DLBCL | ORR 29.3% CR 17.1% DOR 4.5 months PFS 2.8 months? |
[137] |
| mTOR | Onatasertib | NCT01177397 | 1 & 2 | 173 | Completed | MM, DLBCL | Acceptable safety PR 17.6% |
[138] |
| PI3K | Acalisib | NCT01705847 | 1 | 39 | Completed | B-cell Lymphomas | ORR 28.6% AEs grade > 3 55.3% |
[139] |
| PI3K | AMG-319 | NCT01300026 | 1 | 28 | Completed | CLL, DLBCL, MCL | AEs grade > 3 25% | [140] |
| PI3K | Buparlisib | NCT01693614 | 2 | 72 | Completed | DLBCL, MCL, FL | ORR 11.5% in DLBCL and 22.7% in MCL | [141] |
| PI3K | Buparlisib | NCT01719250 | Early 1 | 7 | Completed | R/R DLBCL, R/R FL, R/R MCL | NA | NA |
| PI3K | Fimepinostat | NCT01742988 | 1 | 106 | Completed | R/R DLBCL | CR 12.5% PR 37.5% SD 37.5% |
[142] |
| PI3K | Idelalisib | NCT03151057 | 1 | 60 | Active | CLL, FL, MCL, DLBCL | NA | NA |
| PI3K | KA2237 | NCT02679196 | 1 | 23 | Completed | B-cell Lymphomas | ORR 37% AEs grade > 3 43% |
[143] |
| PI3K | Parsaclisib | NCT03688152 | 1 | 9 | Completed | R/R DLBCL | NA | NA |
| PI3K | Parsaclisib | NCT03314922 | 1 | 17 | Active | B-cell Lymphomas | NA | NA |
| PI3K | Parsaclisib | NCT02998476 | 2 | 60 | Completed | R/R DLBCL | ORR 25.5% DOR 6.2 months |
[144] |
| PI3K | Tenalisib | NCT02017613 | 1 | 35 | Completed | B-cell Lymphomas | ORR 19% CR 6% PR 13% |
[145] |
| PI3K | Umbralisib | NCT01767766 | 1 | 90 | Completed | NHL, CLL | ORR 24% CR 8% PR 16% AEs grade > 3 in less than 5% |
[146,147] |
| SYK | Fostamatinib | NCT00446095 | 1 & 2 | 81 | Completed | B-cell Lymphomas | ORR 22% in DLBCL and 11% in MCL PFS 4.2 months |
[148] |
Abbreviations: FL, follicular lymphoma; DLBCL, diffuse large B-cell lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; NHL, non-Hodgkin lymphoma; CLL, chronic lymphocytic leukemia; MM, multiple myeloma; WM, waldenstrom’s macroglobulinemia; ORR, overall response rate; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; DOR, duration of response; PFS, progression-free survival; OS, overall survival; AEs, adverse effects; NA, not available.