Table 3 Targeted drugs and clinical trials related to the PI3K-AKT-mTOR, JAK-STAT, NOTCH, and NF-κB signaling pathways
Drug | Disease | Trial name | Phase | Status | ORR/CR | NCT# | Reference |
|---|---|---|---|---|---|---|---|
PI3k-AKT-mTOR pathway | |||||||
Idelalisib | A p110δ-selective inhibitor | ||||||
Idelalisib | Relapsed or refractory HL | Safety and efficacy of idelalisib in relapsed or refractory Hodgkin’s lymphoma | 2 | Completed | 68%/4% | NCT01393106 | |
Idelalisib | Idolent B-NHLs | Efficacy and safety study of idelalisib in subjects with indolent B-cell non-Hodgkin’s lymphoma (DELTA) | 2 | Completed | 57%/6% | NCT01282424 | |
Idelalisib, obinutuzumab | Relapsed or refractory FL | Idelalisib plus obinutuzumab in patients with relapsed or refractory follicular lymphoma (GAUDEALIS) | 2 | Not yet recruiting | – | NCT03890289 | – |
Idelalisib, BR | Relapsed or refractory indolent B-NHLs/MCL/CLL | Study to investigate idelalisib in combination with chemotherapeutic agents, immunomodulatory agents and anti-CD20 monoclonal antibody in subjects with relapsed or refractory indolent B-cell non-Hodgkin’s lymphoma, mantle cell lymphoma or chronic lymphocytic leukemia | 1 | Completed | 81%/32% | NCT01088048, NCT01090414 | – |
Idelalisib, lenalidomide | Recurrent FL | Lenalidomide and idelalisib in treating patients with recurrent follicular lymphoma | 1 | Completed | NA | NCT01644799 | |
Idelalisib, lenalidomide | Relapsed or refractory MCL | Lenalidomide with or without idelalisib in treating patients with relapsed or refractory mantle cell lymphoma | 1 | Completed | NA | NCT01838434 | |
Umbralisib | A second-generation p110δ-selective inhibitor | ||||||
Umbralisib, ibrutinib | CLL/MCL | A phase 1 safety and efficacy study of the PI3K-delta Inhibitor umbralisib and ibrutinib in patients with CLL or MCL | 1 | Completed | MCL, 67%/19%; CLL, 90%/29% | NCT02268851 | |
Duvelisib | A PI3Kδ/γ inhibitor | ||||||
Duvelisib | Refractory iNHLs | A phase 2 study of duvelisib in subjects with refractory indolent non-Hodgkin’s lymphoma (DYNAMO) | 2 | Active, not recruiting | 46%/NA | NCT01882803 | |
Temsirolimus | A mTOR inhibitor | ||||||
Temsirolimus | MCL | Study evaluating temsirolimus in mantle cell lymphoma (OPTIMAL) | 3 | Completed | 38%/3% | NCT00117598 | |
Temsirolimus vs. ibrutinib | Relapsed or refractory MCL | Study of ibrutinib versus temsirolimus in patients with relapsed or refractory mantle cell lymphoma who have received at least one prior therapy | 3 | Completed | NA | NCT01646021 | |
Temsirolimus, rituximab, DHAP | Relapsed or refractory DLBCL | Temsirolimus, rituximab, and DHAP for relapsed or refractory diffuse large B-cell lymphoma (STORM) | 2 | Unknown | – | NCT01653067 | |
Everolimus | An oral mTOR inhibitor | ||||||
Everolimus, itacitinib | HL | Everolimus plus itacitinib in Hodgkin’s lymphoma | 1/2 | Recruiting | – | NCT03697408 | – |
Everolimus, panobinostat | Relapsed or refractory lymphoma | Everolimus plus panobinostat in patients with relapsed or refractory lymphoma | 1/2 | Completed | NA | NCT00967044 | – |
JAK-STAT pathway | |||||||
Ruxolitinib | A JAK1/2 inhibitor | ||||||
Ruxolitinib | Relapsed or refractory cHL | A phase 2 study of oral JAK1/JAK2 inhibitor ruxolitinib in adult patients with relapsed or refractory classical Hodgkin’s lymphoma (HIJAK) | 2 | Completed | 9.4%/0% | NCT01877005 | |
Ruxolitinib, nivolumab | Relapsed or refractory cHL | Nivolumab with ruxolitinib in relapsed or refractory classical Hodgkin’s lymphoma | 1 | Recruiting | – | NCT03681561 | – |
Itacitinib | A JAK1 selective inhibitor | ||||||
Itacitinib, everolimus | HL | Itacitinib plus everolimus in Hodgkin’s lymphoma | 1/2 | Recruiting | – | NCT03697408 | – |
Itacitinib, ibrutinib | Relapsed or refractory DLBCL | A study of itacitinib in combination with ibrutinib in subjects with relapsed or refractory diffuse large B-cell lymphoma | 1/2 | Active, not recruiting | – | NCT02760485 | – |
NOTCH signaling pathway | |||||||
BMS-906024 | A γ-secretase inhibitor | ||||||
BMS-906024, dexamethasone | T-ALL/T-LBL | Study to evaluate the safety and tolerability of weekly intravenous doses of BMS-906024 in subjects with acute T-cell lymphoblastic leukemia or T-cell lymphoblastic lymphoma | 1 | Completed | NA | NCT01363817 | – |
LY3039478 | A γ-secretase inhibitor | ||||||
LY3039478, dexamethasone | T-ALL/T-LBL | A study of LY3039478 in combination with dexamethasone in participants with acute T-cell lymphoblastic leukemia or T-cell lymphoblastic lymphoma | 1/2 | Completed | – | NCT02518113 | – |
CB-103 | A pan-NOTCH inhibitor | ||||||
CB-103 | Solid tumors/NHLs | Study of CB-103 in adult patients with advanced or metastatic solid tumors and hematological malignancies | 1/2 | Recruiting | – | NCT03422679 | – |
NF-κB pathway | |||||||
Pevonedistat | A NEDD8-activating enzyme inhibitor | ||||||
Pevonedistat, ibrutinib | Relapsed or refractory CLL/NHL | Pevonedistat and ibrutinib in treating participants with relapsed or refractory chronic lymphocytic leukemia or non-Hodgkin’s lymphoma | 1 | Recruiting | – | NCT03479268 | – |
SNX-5422 | A synthetic, novel, small-molecule HSP90 Inhibitor | ||||||
SNX-5422 | Solid tumors/lymphomas | Safety study of SNX-5422 to treat solid tumor cancers and lymphomas | 1 | Completed | NA | NCT00647764 | – |
SNX-5422 | Solid tumors/lymphomas | SNX-5422 to treat solid tumor cancers and lymphoma | 1 | Completed | NA | NCT00644072 | – |
