Table 2 Targeted drugs and clinical trials related to SYK and BTK
Drug | Disease | Trial name | Phase | Status | ORR/CR | NCT# | Reference |
|---|---|---|---|---|---|---|---|
SYK inhibitor | |||||||
Fostamatinib | A SYK inhibitor | ||||||
Fostamatinib | Relapsed or refractory B-NHLs | Efficacy and safety study of fostamatinib tablets to treat B-cell lymphoma | 1/2 | Completed | DLBCL, 22%; FL, 10%; MCL, 11% | NCT00446095 | |
TAK-659 | A SYK inhibitor | ||||||
TAK-659 | Relapsed or refractory DLBCL | TAK-659 in participants with relapsed or refractory diffuse large B-cell lymphoma | 2 | Active, not recruiting | – | NCT03123393 | – |
TAK-659, venetoclax | Relapsed or refractory NHL | A study of TAK-659 in combination with venetoclax for adult participants with previously treated non-Hodgkin’s lymphoma | 1 | Active, not recruiting | – | NCT03357627 | – |
TAK-659, R-CHOP | High-risk DLBCL | Combination chemotherapy and TAK-659 as frontline treatment in treating patients with high-risk diffuse large B-cell lymphoma | 1 | Recruiting | – | NCT03742258 | – |
Entospletinib | A SYK inhibitor | ||||||
Entospletinib | Relapsed or refractory hematologic malignancies | Entospletinib in adults with relapsed or refractory hematologic malignancies | 2 | Active, not recruiting | – | NCT01799889 | – |
Entospletinib, obinutuzumab | Relapsed or refractory CLL/SLL, NHL | Entospletinib and obinutuzumab in treating patients with relapsed chronic lymphocytic leukemia, small lymphocytic lymphoma, or non-Hodgkin’s lymphoma | 1/2 | Recruiting | – | NCT03010358 | – |
Entospletinib, idelalisib | Relapsed or refractory hematologic malignancies | Entospletinib in combination with idelalisib in adults with relapsed or refractory hematologic malignancies | 2 | Terminated | – | NCT01796470 | |
Cerdulatinib | A dual SYK/JAK inhibitor | ||||||
Cerdulatinib | CLL/SLL, NHL | Phase 1/2 dose-escalation study in CLL/SLL or NHL | 1/2 | Recruiting | – | NCT01994382 | – |
Cerdulatinib | Relapsed or refractory PTCL | CELTIC-1: a phase 2/3 study of cerdulatinib in patients with relapsed or refractory peripheral T-cell lymphoma | 2/3 | Not yet recruiting | – | NCT04021082 | – |
BTK inhibitor | |||||||
Ibrutinib | Suppressing BTK enzymatic activity through a irreversible covalent bond with a cysteine residue in the BTK active site | ||||||
Ibrutinib | Relapsed or refractory B-NHLs | Study of the safety and tolerability of ibrutinib in patients with recurrent B-cell lymphoma | 1/2 | Completed | 60%/16% | NCT00849654 | |
Ibrutinib | Relapsed or refractory DLBCL | Safety and efficacy study of a Bruton’s tyrosine kinase inhibitor in subjects with relapsed or refractory diffuse large B-cell lymphoma | 1/2 | Completed | ABC-DLBCL, 37%/16%; GCB-DLBCL, 5%/0% | NCT01325701 | |
Ibrutinib | Relapsed or refractory FL | Ibrutinib in treating patients with relapsed or refractory follicular lymphoma | 2 | Active, not recruiting | 37.5%/12.5% | NCT01849263 | |
Ibrutinib | Relapsed or refractory MZL | Study of the Bruton’s tyrosine kinase inhibitor in subjects with relapsed or refractory marginal zone lymphoma | 2 | Completed | 48%/3% | NCT01980628 | |
Ibrutinib | Relapsed or refractory MCL | Safety and efficacy of ibrutinib in participants with relapsed or refractory mantle cell lymphoma | 2 | Completed | 68%/21% | NCT01236391 | |
Ibrutinib, nivolumab | Relapsed or refractory B-NHLs, CLL/SLL | A study to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the combination of ibrutinib with nivolumab in participants with hematologic malignancies | 1/2 | Active, not recruiting | DLBCL, 36%/16%; FL, 33%/10%; CLL/SLL, 61%/0% | NCT02329847 | |
Ibrutinib, venetoclax | MCL | Venetoclax plus ibrutinib in mantle cell lymphoma (AIM) | 2 | Completed | 71%/62% | NCT02471391 | |
Ibrutinib, lenalidomide, rituximab | Untreated and unfit elderly DLBCL | Study evaluating the safety and efficacy of ibrutinib, lenalidomide, and rituximab in untreated and unfit elderly patients with DLBCL | 2 | Recruiting | – | NCT03949062 | – |
Ibrutinib, lenalidomide, rituximab | Untreated FL | Ibrutinib, lenalidomide, and rituximab in treating patients with previously untreated stage II–IV follicular lymphoma | 1 | Active, not recruiting | 95%/NA | NCT01829568 | |
Ibrutinib, lenalidomide, rituximab | Relapsed or refractory MCL | A trial of ibrutinib, lenalidomide, and rituximab for patients with relapsed or refractory mantle cell lymphoma (PHILEMON) | 2 | Recruiting | 76%/56% | NCT02460276 | |
Ibrutinib, R-CHOP | Untreated CD20+ B-NHLs | A study combining ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients With CD20+ B-cell non-Hodgkin’s lymphoma | 1 | Completed | 100%/NA | NCT01569750 | |
Ibrutinib, R-CHOP vs. placebo, R-CHOP | Untreated non-GCB DLBCL | A study of the Bruton’s tyrosine kinase inhibitor, ibrutinib, in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with newly diagnosed non-germinal center B-cell subtype of diffuse large B-cell lymphoma | 3 | Active, not recruiting | Ibrutinib, R-CHOP, NA/67.3%; placebo, R-CHOP, NA/68.0% | NCT01855750 | – |
Ibrutinib, high-dose methotrexate, rituximab | Relapsed or refractory CNSL | Bruton’s tyrosine kinase inhibitor, ibrutinib, in patients with relapsed or refractory primary central nervous system lymphoma and relapsed or refractory secondary central nervous system lymphoma | 1/2 | Active, not recruiting | Phase 1 part: 80%/53% | NCT02315326 | |
Acalabrutinib | A new, irreversible and second-generation BTK inhibitor with enhanced efficacy and improved off-target effect | ||||||
Acalabrutinib | Relapsed or refractory MCL | An open-label, phase 2 study of acalabrutinib in subjects with mantle cell lymphoma | 2 | Active, not recruiting | 81%/40% | NCT02213926 | |
Acalabrutinib | Relapsed CLL | Acalabrutinib, a novel bruton tyrosine kinase inhibitor, for treatment of chronic lymphocytic leukemia | 1/2 | Active, not recruiting | 95%/0% | NCT02029443 | |
Acalabrutinib vs. ibrutinib | Previously treated high-risk CLL | Study of acalabrutinib versus ibrutinib in previously treated subjects with high-risk CLL | 3 | Active, not recruiting | – | NCT02477696 | – |
Acalabrutinib, pembrolizumab | Hematologic malignancies | Acalabrutinib in combination with pembrolizumab, for treatment of hematologic malignancies (KEYNOTE145) | 1/2 | Active, not recruiting | – | NCT02362035 | – |
Acarabrutinib, venetoclax | Relapsed or refractory MCL | Acalabrutinib and venetoclax in treating patients with relapsed or refractory mantle cell lymphoma | 2 | Recruiting | – | NCT03946878 | – |
Acalabrutinib, BR vs. placebo, BR | Untreated MCL | A study of bendamustine and rituximab alone versus in combination with acalabrutinib in subjects with previously untreated mantle cell lymphoma | 3 | Recruiting | – | NCT02972840 | – |
Acalabrutinib, R-CHOP | Untreated DLBCL | A combination of acalabrutinib with R-CHOP for patient with diffuse large B-cell lymphoma (ACCEPT) | 1/2 | Recruiting | – | NCT03571308 | – |
acalabrutinib, R-ICE | relapsed or refractory DLBCL | Acalabrutinib plus R-ICE for relapsed or refractory diffuse large B-cell lymphoma | 2 | Not yet recruiting | – | NCT03736616 | – |
Zanubrutinib | A second-generation BTK inhibitor showing distinguished kinase selectivity and lower side effect | ||||||
Zanubrutinib | B-cell lymphoid malignancies | Study of the safety and pharmacokinetics of zanubrutinib in subjects with B-cell lymphoid malignancies | 1 | Active, not recruiting | total, 96.2%/2.6%; treatment-naïve, 100%/4.5%; relapsed or refractory, 94.6%/1.8% | NCT02343120 | |
Zanubrutinib | Relapsed or refractory non-GCB DLBCL | Study of BTK inhibitor zanubrutinib in subjects with relapsed or refractory non-GCB type diffuse large B-cell lymphoma | 2 | Active, not recruiting | – | NCT03145064 | – |
Zanubrutinib | Relapsed or refractory MZL | Study of zanubrutinib in patients with marginal zone lymphoma | 2 | Recruiting | – | NCT03846427 | – |
Zanubrutinib | Relapsed or refractory MCL | Study to evaluate efficacy and safety of zanubrutinib in subjects with relapsed or refractory mantle cell lymphoma | 2 | Active, not recruiting | – | NCT03206970 | – |
Zanubrutinib vs. ibrutinib | Relapsed or refractory CLL | A study of zanubrutinib versus ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (ALPINE) | 3 | Recruiting | – | NCT03734016 | – |
Zanubrutinib vs. ibrutinib | WM | A study comparing zanubrutinib and ibrutinib in subjects with Waldenström’s macroglobulinemia | 3 | Active, not recruiting | – | NCT03053440 | – |
Tirabrutinib | A highly selective irreversible BTK inhibitor | ||||||
Tirabrutinib | relapsed or refractory NHLs/CLL | Phase 1 study of tirabrutinib given as monotherapy in patients with relapsed or refractory NHLs and CLL | 1 | Completed | ABC-DLBCL, 35%/9.7%; MCL, 92%/46%; CLL, 96%/NA | NCT01659255 | |
M7583 | A novel irreversible BTK inhibitor | ||||||
M7583 | B-cell malignancies | BTK inhibitor in B-cell malignancies | 1/2 | Active, not recruiting | – | NCT02825836 | – |
Vecarutinib | A noncovalent or reversible BTK inhibitor | ||||||
Vecarutinib | B-NHLs | Safety and antitumor activity of vecabrutinib in B-lymphoid cancers | 1/2 | Recruiting | – | NCT03037645 | – |
ARQ-531 | A reversible BTK inhibitor with off-target activity against Src and Tec family of protein tyrosine kinases | ||||||
ARQ-531 | Hematologic malignancies | Safety and antitumor activity of ARQ-531 in hematologic malignancies | 1 | Recruiting | – | NCT03162536 | – |
ICP-022 | A novel BTK inhibitor | ||||||
ICP-022 | Relapsed or refractory B-cell malignancies | Dose escalation of ICP-022 in patients with relapsed or refractory B-cell malignancies | 1 | Recruiting | – | NCT04014205 | – |
LOXO-305 | A novel, selective noncovalent or reversible BTK inhibitor | ||||||
LOXO-305 | CLL/SLL, NHLs | A study of oral LOXO-305 in patients with previously treated CLL/SLL or NHLs | 1/2 | Recruiting | – | NCT03740529 | – |
