Select clinical trials of PI3K in CLL/SLL or other hematologic malignancies with focus on next-generation agents, novel–novel combinations, and/or alternative dosing
| PI3Ki . | Phase (ClinicalTrials.gov identifier) . | Population . | Dosing/combination . | Notes . |
|---|---|---|---|---|
| Duvelisib | Phase 1 (NCT03534323) | R/R CLL | Duvelisib plus venetoclax | Fixed duration; dosing can be stopped if reaching MRD negativity at 1 y |
| Duvelisib | Phase 2 (NCT03961672) | R/R CLL | Duvelisib is administered at standard dosing during a 3-mo induction followed by twice-weekly maintenance | Intermittent dosing after induction continuous cycles |
| Umbralisib | Phase 3 UNITY (NCT02612311) | Frontline CLL | Umbralisib + ublituximab vs obinutuzumab + chlorambucil | Press release for meeting primary endpoint |
| Umbralisib | Phase 1 (NCT02268851) | R/R CLL and MCL | Umbralisib and ibrutinib | First clinical data on safety of doublet BTKi and PI3Kδi53 |
| Umbralisib | Phase 1 ((NCT02006485) | Frontline and R/R CLL/SLL and B-cell NHL | Umbralisib, ublituximab, and ibrutinib | Triplet therapy combination safety data for anti-CD20 plus BTKi and PI3Kδi54 |
| Umbralisib | Phase 2 (NCT04016805) | Patients with CLL currently on ibrutinib or venetoclax | Umbralisib and ublituximab | Addition of PI3Ki combination to increase MRD rates with addition of umbralisib and ublituximab to ibrutinib or venetoclax |
| Umbralisib | Phase 2 (NCT03801525) | Frontline CLL | Ublituximab, umbralisib, and venetoclax | Frontline triplet with limited treatment duration |
| ME-401 | Phase 1 | ME-401 as monotherapy or in combination with R | Alternate dosing strategy (continuous → intermittent dosing) effective with reduced toxicities43 | |
| ME-401 | Phase 1 (NCT02914938) | R/R CLL/SLL or B-cell NHL | ME-401 alone or in combination with rituximab or zanubrutinib in R/R CLL/SLL or other |
| PI3Ki . | Phase (ClinicalTrials.gov identifier) . | Population . | Dosing/combination . | Notes . |
|---|---|---|---|---|
| Duvelisib | Phase 1 (NCT03534323) | R/R CLL | Duvelisib plus venetoclax | Fixed duration; dosing can be stopped if reaching MRD negativity at 1 y |
| Duvelisib | Phase 2 (NCT03961672) | R/R CLL | Duvelisib is administered at standard dosing during a 3-mo induction followed by twice-weekly maintenance | Intermittent dosing after induction continuous cycles |
| Umbralisib | Phase 3 UNITY (NCT02612311) | Frontline CLL | Umbralisib + ublituximab vs obinutuzumab + chlorambucil | Press release for meeting primary endpoint |
| Umbralisib | Phase 1 (NCT02268851) | R/R CLL and MCL | Umbralisib and ibrutinib | First clinical data on safety of doublet BTKi and PI3Kδi53 |
| Umbralisib | Phase 1 ((NCT02006485) | Frontline and R/R CLL/SLL and B-cell NHL | Umbralisib, ublituximab, and ibrutinib | Triplet therapy combination safety data for anti-CD20 plus BTKi and PI3Kδi54 |
| Umbralisib | Phase 2 (NCT04016805) | Patients with CLL currently on ibrutinib or venetoclax | Umbralisib and ublituximab | Addition of PI3Ki combination to increase MRD rates with addition of umbralisib and ublituximab to ibrutinib or venetoclax |
| Umbralisib | Phase 2 (NCT03801525) | Frontline CLL | Ublituximab, umbralisib, and venetoclax | Frontline triplet with limited treatment duration |
| ME-401 | Phase 1 | ME-401 as monotherapy or in combination with R | Alternate dosing strategy (continuous → intermittent dosing) effective with reduced toxicities43 | |
| ME-401 | Phase 1 (NCT02914938) | R/R CLL/SLL or B-cell NHL | ME-401 alone or in combination with rituximab or zanubrutinib in R/R CLL/SLL or other |
MRD, minimal residual disease defined as by less than one CLL cell in the peripheral blood or bone marrow per 10,000 leukocytes (<10-4)