Clinical results of select kinase inhibitors in CLL
| . | Dasatinib . | Fostamatinib (R788; R406) . | GS-1101 (CAL-101) . | Ibrutinib (PCI-32 765) . |
|---|---|---|---|---|
| Kinase target | LYN, BTK, ABL | SYK, FLT3, KIT, LCK, JAK1, JAK3 | PI3Kδ | BTK |
| Dose | 140 mg oral daily | 200 mg oral twice a day | 150 mg oral twice a day | 420 mg oral daily (840 mg used in some studies) |
| CLL patients | 15 relapsed | 11 relapsed | 54 relapsed | 76 relapsed in 2 studies; 31 elderly, treatment-naive |
| Reponses | Best response: nodal response in 27%, 20% PR; PFS 7.5 months | At 2 months: nodal response in 55%; PFS 6.4 months | 80% nodal response; 26% PR*; PFS 15 months | 60%-73% OR*; PFS at 12 months ≥ 86% |
| Common AEs | Myelosuppression, nausea/vomiting, diarrhea, pleural effusions | Diarrhea, fatigue, nausea, hypertension | URI, increase in LFTs | Diarrhea, nausea, fatigue, URI, muscle spasms, arthralgia, peripheral edema, pyrexia |
| Grade 3/4 AEs | Neutropenia, thrombocytopenia | In > 5% patients: neutropenia, anemia, hypertension | Pneumonia 24%, neutropenia, thrombocytopenia, anemia, | Infections 26%; neutropenia and thrombocytopenia in < 10% |
| Stage of development in CLL | Phase 2 completed | Phase 2 completed | Phase 1 completed, phase 2/3 ongoing | Phase 1 completed, phase 2/3 ongoing |
| Clinical development in other indications | Approved for CML | Pivotal phase 3 study in RA completed | Indolent and aggressive NHL | Indolent and aggressive NHL and MCL |
| . | Dasatinib . | Fostamatinib (R788; R406) . | GS-1101 (CAL-101) . | Ibrutinib (PCI-32 765) . |
|---|---|---|---|---|
| Kinase target | LYN, BTK, ABL | SYK, FLT3, KIT, LCK, JAK1, JAK3 | PI3Kδ | BTK |
| Dose | 140 mg oral daily | 200 mg oral twice a day | 150 mg oral twice a day | 420 mg oral daily (840 mg used in some studies) |
| CLL patients | 15 relapsed | 11 relapsed | 54 relapsed | 76 relapsed in 2 studies; 31 elderly, treatment-naive |
| Reponses | Best response: nodal response in 27%, 20% PR; PFS 7.5 months | At 2 months: nodal response in 55%; PFS 6.4 months | 80% nodal response; 26% PR*; PFS 15 months | 60%-73% OR*; PFS at 12 months ≥ 86% |
| Common AEs | Myelosuppression, nausea/vomiting, diarrhea, pleural effusions | Diarrhea, fatigue, nausea, hypertension | URI, increase in LFTs | Diarrhea, nausea, fatigue, URI, muscle spasms, arthralgia, peripheral edema, pyrexia |
| Grade 3/4 AEs | Neutropenia, thrombocytopenia | In > 5% patients: neutropenia, anemia, hypertension | Pneumonia 24%, neutropenia, thrombocytopenia, anemia, | Infections 26%; neutropenia and thrombocytopenia in < 10% |
| Stage of development in CLL | Phase 2 completed | Phase 2 completed | Phase 1 completed, phase 2/3 ongoing | Phase 1 completed, phase 2/3 ongoing |
| Clinical development in other indications | Approved for CML | Pivotal phase 3 study in RA completed | Indolent and aggressive NHL | Indolent and aggressive NHL and MCL |
AE indicates adverse event; URI, upper respiratory tract infection; LFT, liver function test; RA, rheumatoid arthritis; NHL, non-Hodgkin lymphoma; and MCL, mantle cell lymphoma
IWCLL criteria.60