Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
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 being studied for use in oncology. It has been evaluated in clinical trials for recurrent glioblastoma multiforme, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, and renal impairment. It is not approved by the FDA and remains in clinical development.
Buparlisib is a small molecule that targets PI3K, a key enzyme in the PI3K/AKT/mTOR signaling pathway involved in cell growth and survival. By inhibiting PI3K, it aims to disrupt cancer cell proliferation. This mechanism is being studied across several cancer types.
Buparlisib is being developed by Novartis AG, a multinational pharmaceutical company traded on the New York Stock Exchange under the ticker symbol NVS. Novartis is conducting clinical trials to evaluate the drug's safety and efficacy in various oncology indications.
Buparlisib has completed Phase 1 and Phase 2 clinical trials. The most advanced study, a Phase 2 trial in relapsed and refractory non-Hodgkin lymphoma, is completed. It is not FDA approved and remains an investigational drug in clinical development.
Buparlisib has been studied in three completed trials: NCT01693614, a Phase 2 study in diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma; NCT01934361, a Phase 1b/2 study in recurrent glioblastoma multiforme; and NCT02048787, a Phase 1 pharmacokinetic study in renal impairment.
Yes, Buparlisib is also known as BKM120. In clinical trial NCT01693614, the drug is referred to as BKM120. This alternative name is used in some research contexts, so patients and researchers may encounter either designation for the same investigational compound.