Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as buparlisib (BKM120), BKM120
Buparlisib · 3 trials · 3 indications
Overall Response rate is the percentage of patients in a cohort who experienced either complete response (CR) or partial response (PR) during their follow-up after treatment start divided by the total percentage of patients included in the corresponding cohort according to Cheson criteria The analysis for each cohort was based on an exact binomial test comparing the ORR to the reference level of 10% (null hypothesis) in the FAS. The test for each cohort used a significance level of 5%. The ORR was presented together with an exact 95% Clopper- Pearson confidence interval. Disease Control Rate (DCR progressive. Disease Control Rate (DCR) was the percentage of patients with CR, PR or SD (stable disease). Patients for whom the best response after treatment start was missing, unknown (UNK) or progressive disease (PD) were considered non-responders and were counted in the denominator for the estimation of the ORR
Measurement of effect of renal impairment on PK of buparlisib by assessment of the maximum plasma concentration (PK parameter Cmax). Cmax directly determined from the plasma concentration-time profiles.
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter AUCinf (area under the plasma concentration-time curve from time 0 to infinity). AUC determined from the plasma concentration-time profile using non-compartmental analysis.
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter AU0-t (area under the plasma-concentration time curve from timepoint 0 to time t). AUC determined from the plasma concentration-time profile using non-compartmental analysis.
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter CL/F (clearance).
Measurement of effect of renal impairment on PK of buparlisib by assessment of the urine clearance CLR.
Maximum Tolerated Dose (MTD) is defined as the highest BKM120 dosage that does not cause medically unacceptable Dose Limiting Toxicities (DLTs) in more than 35% of the treated patients during the first cycle of treatment. DLT is defined as treatment-related toxicity occurring during the phase Ib cycle 1 and meeting specific protocol-predefined criteria. The information will be integrated in a Bayesian logistic regression model with overdose control to estimate the MTD.
12-week Progression Free Survival (PFS) is defined as the percentage of patients who are progression free 12 weeks after the date of the start of the treatment ("success"). Patients who progressed, died or discontinued within the 12 weeks of observation are counted as "failure".
Progression Free Survival (PFS) is defined as the time from date of randomization to the date of the event, which is the first radiologically documented disease progression \[per local investigator assessment according to Response Assessment in Neuro-Oncology (RANO) criteria\] or death due to any cause.
| Arm | Type | Description |
|---|---|---|
| DLBCL Cohort | EXPERIMENTAL | Diffuse large B-cell lymphoma cohort |
| MCL Cohort | EXPERIMENTAL | Mantle cell lymphoma cohort |
| FL Cohort | EXPERIMENTAL | Follicular lymphoma cohort |
| Moderate renal impairment group | EXPERIMENTAL | Subjects with moderate renal impairment defined as eGFR of 30-59 mL/min/1.73m2 at screening can be enrolled in this group |
| Severe renal impairment group | EXPERIMENTAL | Subjects with severe renal impairment defined as eGFR of 15-29 mL/min/1.73m2 at screening can be enrolled in this group |
| Matching healthy control group | EXPERIMENTAL | Subjects with normal renal function defined as eGFR ≥ 90 mL/min/1.73m2 at screening and matching to the renal impaired subject based on gender, race, age, and weight can be enrolled in this group. |
| Lomustine+ buparlisib (Phase Ib) | EXPERIMENTAL | - |
| carboplatin+ buparlisib (Phase Ib) | EXPERIMENTAL | - |
| lomustine+ buparlisib (Phase II) | EXPERIMENTAL | - |
| lumustine + placebo (Phase II) | PLACEBO_COMPARATOR | - |
| carboplatin+ buparlisib (Phase II) | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Buparlisib | DRUG | 100 mg hard gelatin capsules administered orally, once daily in cycles of 28 days |
| carboplatin | DRUG | Carboplatin intravenous infusion will be administered at a dose of AUC 5 in a 21 day cycle (every 3 weeks). |
| lomustine | DRUG | Lomustine will be administered as a single oral dose of 100 mg/m² every 6 weeks in a 42 day cycles. |
| placebo | DRUG | Placebo will be administered orally on a continuous QD dosing schedule for cycles of 42 days. Buparlisib matching placebo is manufactured as 10 mg and 50 mg hard gelatin capsules. |
Inclusion Criteria: 1. Patient had a histologically confirmed diagnosis of mantle cell lymphoma, follicular lymphoma, or diffuse large B cell lymphoma. 2. Patient had relapsed or refractory disease and received at least one prior therapy. 3. Patient with diffuse large B cell lymphoma had received o...
Buparlisib is an investigational small molecule developed by Novartis AG (ticker NVS) for oncology indications. It has been studied in diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, recurrent glioblastoma multiforme, and renal impairment. It is a Phase 2 agent and is not described as approved.
Buparlisib has been studied in relapsed and refractory non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, as well as in recurrent glioblastoma multiforme and in subjects with renal impairment. These are investigational uses in clinical trials, not approved indications.
Buparlisib targets the phosphoinositide 3-kinase (PI3K) subunits PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, and PIK3R2. It acts as an inhibitor of these targets. This mechanism underlies its investigation in B-cell lymphomas and glioblastoma.
Buparlisib is developed by Novartis AG, which trades under the ticker NVS. Novartis sponsored the clinical trials of the compound, including the Phase 2 study in relapsed and refractory non-Hodgkin lymphoma and the Phase 1 renal impairment pharmacokinetic study.
Buparlisib is in Phase 2 development. Its trials include a completed Phase 2 study in relapsed and refractory non-Hodgkin lymphoma, a completed Phase 1b/2 study in recurrent glioblastoma multiforme, and a completed Phase 1 pharmacokinetic study in renal impairment. It is investigational and not approved.
Buparlisib has been evaluated in NCT01693614, a Phase 2 safety and efficacy study in relapsed and refractory non-Hodgkin lymphoma with 72 patients, NCT01934361, a Phase 1b/2 study with carboplatin or lomustine in recurrent glioblastoma multiforme, and NCT02048787, a Phase 1 pharmacokinetic study in renal impairment. All are completed.
Yes, Buparlisib is also known as BKM120. BKM120 is the alternate code name used for the same compound in trial titles and publications, including the Phase 2 study of BKM120 in relapsed and refractory non-Hodgkin lymphoma.