Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LBH589 · 18 trials · 23 indications
Overall response rate is percentage of participants with complete (CR), very good partial (VGPR), partial (PR), or minimal response (MR) as best response during treatment. CR * Disappearance of monoclonal protein by immunofixation * No histologic evidence of bone marrow involvement * Resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM. * Second immunofixation required for confirmation. VGPR -At least 90% reduction of serum monoclonal IgM concentration on protein electrophoresis. PR * At least 50% reduction of serum monoclonal IgM concentration on protein electrophoresis and at least 50% decrease in adenopathy/organomegaly on physical examination or on CT scan. * No new symptoms or signs of active disease. MR * At least 25% but less than 50% reduction of serum monoclonal IgM by protein electrophoresis. * No new symptoms or signs of active disease.
nCR plus CR rate after 8 cycles of therapy as defined by the modified European Society for Bone and Marrow Transplantation (EBMT) criteria per investigator assessment as the proportion of participants with nCR or CR as their best overall response.
Progression-free survival was defined as the interval from the date of first treatment with panobinostat until the date that disease progression or death occurred. Progressive disease (PD): 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.
MTD for Capecitabine, BID
oral dose of \[14C\] LBH589
Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for consecutive dosing schedule (MWF weekly). A 3-parameter version of a Bayesian logistic regression model with overdose control (Babb, Rogatko, and Zacks 1998) was used during the dose escalation phase for dose level selection and determination of the MTD.
Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for intermittent dosing schedule (MWF weekly). A 3-parameter version of a Bayesian logistic regression model with overdose control (Babb, Rogatko, and Zacks 1998) was used during the dose escalation phase for dose level selection and determination of the MTD.
| Arm | Type | Description |
|---|---|---|
| LBH589 | EXPERIMENTAL | 30 mg three days a week (Mondays, Wednesdays and Fridays). 1 cycle was 28 days Dose modifications for attributable toxicities allowed for reduction to: * 25 mg, 20 mg three times a week every week * Or 20 mg three times a week every other week. No dose re-escalation was allowed. * The protocol was amended on 6/15/2010 because of concerns of toxicity to allow a starting dose of 25 mg; 12/36 (33%) patients were enrolled on the 25 mg dose. |
| LBH589 + bortezomib + dexamethasone | EXPERIMENTAL | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| LBH589 plus Rituximab | EXPERIMENTAL | - |
| Treatment | OTHER | LBH589 will be administered orally at a dose of 45 mg (1 - 5 mg capsule and 2 - 20 mg capsules) on Monday and Thursday of each week (twice weekly). To enable patients to undergo cardiac monitoring, all patients must begin treatment on a Monday, and continue Monday/Thursday dosing during subsequent treatment cycles. Patients with objective response or stable disease after re-evaluation at week 8 will continue LBH589 at the same dose until disease progression, unacceptable toxicity and/or at the discretion of the investigator. |
| LBH589 with Capecitabine | EXPERIMENTAL | MTD, LBH589 with Capecitabine |
| LBH589 and Lapatinib | EXPERIMENTAL | LBH589 and Lapatinib |
| LBH589, Capecitabine and Lapatinib | EXPERIMENTAL | LBH589, Capecitabine and Lapatinib (Breast Cancer Patients) |
| HDACi | EXPERIMENTAL | - |
| IV LBH589 + trastuzumab + paclitaxel | EXPERIMENTAL | i.v. panobinostat |
| Oral LBH589 + trastuzumab + paclitaxel | EXPERIMENTAL | oral panobinostat |
| LBH589 (Panobinostat) | EXPERIMENTAL | - |
| PAN 5 mg | EXPERIMENTAL | Panobinostat 5 mg |
| PAN 10 mg | EXPERIMENTAL | Panobinostat 10 mg |
| PAN 20 mg | EXPERIMENTAL | Panobinostat 20 mg |
| PAN 25 mg | EXPERIMENTAL | Panobinostat 25 mg |
| Panobinostat (LBH589) | EXPERIMENTAL | - |
| Arm 1, Group X | EXPERIMENTAL | - |
| Arm 1, Group Y | EXPERIMENTAL | - |
| Arm 2, Group X | EXPERIMENTAL | - |
| Arm 2, Group Y | EXPERIMENTAL | Panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), every other week, as part of a 28-day treatment cycle. Group Y is a sub-arm, based on disease indication. |
| Name | Type | Description |
|---|---|---|
| LBH589 | DRUG | - |
| LBH589 (panobinostat) | DRUG | Panobinostat (PAN) capsules were supplied at dose strengths of 10 mg and 15 mg. and dosed at 20mg during treatment phase 1 (21 days) and treatment phase 2 (42 days) |
| bortezomib | DRUG | Bortezomib (BTZ) s.c: 1.3 mg/m2 was administered during both treatment phase 1 (21 days) \& treatment phase 2 (42 days). |
| dexamethasone | DRUG | Dexamethasone (Dex): 20mg tablets taken during both treatment phase 1 (21 days \& treatment phase 2 (42 days) |
| Rituximab | DRUG | Patients randomized to Arm B will receive IV rituximab at a dose of 375 mg/m2 in combination with oral LBH589. Rituximab should be administered on the same day as LBH589, after the patient has taken their LBH589 dose. The appropriate amount of solution should be withdrawn from the vial for the following calculation: Volume (mL) = BSA (m2) × dose (375 mg/m2) / concentration of reconstituted solution ml/mL (100 mg/10 mL and/or 500 mg/50 mL). |
| Capecitabine | DRUG | Capecitabine will be administered orally twice daily for 14 days out of every 21 days. |
| Lapatinib | DRUG | Lapatinib, 1000 mg PO daily will be added to this combination. |
| IV LBH589 | DRUG | - |
| Oral LBH589 | DRUG | - |
| trastuzumab | DRUG | - |
| paclitaxel | DRUG | - |
| Lenalidomide | COMBINATION_PRODUCT | Lenalidomide 5mg or 25 mg |
| LBH589 (i.v. panobinostat) | DRUG | i.v. LBH589 dose levels: 10, 15, or 20 mg/m2 i.v. docetaxel 75 or 60 mg/m2 oral prednisone 5mg bid. LBH589 i.v. administered on days 1 and 8 in combination with docetaxel i.v. on day 1 and prednisone p.o 5mg bid every day of a 21-day cycle |
Inclusion Criteria: * Male or female patients aged 18 years or older * Must have received prior therapy for their WM, any number of prior therapies is allowed * Must have symptomatic relapsed or refractory WM * Measurable monoclonal IgM protein in the blood and presence of lymphoplasmacytic cells i...
LBH589 is an investigational small molecule being studied for the treatment of multiple cancers, including renal cell carcinoma, breast cancer, prostate cancer, diffuse large B cell lymphoma, and Waldenstrom's macroglobulinemia. It has also been evaluated in patients with advanced solid tumors and certain hematological malignancies.
LBH589 is being developed by Novartis AG, a multinational pharmaceutical company traded on the New York Stock Exchange under the ticker symbol NVS. The drug is an oncology small molecule that has been investigated in clinical trials for various tumor types.
LBH589 has completed Phase 1 and Phase 2 clinical trials. The completed trials include two Phase 1 studies and two Phase 2 studies. The drug is not approved and remains investigational, with no active trials currently listed.
LBH589 has been studied in four completed clinical trials. These include NCT00472368 and NCT00503451, both Phase 1 studies in advanced solid tumors, and NCT00550277 and NCT00936611, both Phase 2 studies in renal cell carcinoma and Waldenstrom's macroglobulinemia, respectively.
LBH589 is also known as panobinostat, a histone deacetylase inhibitor. The drug has been investigated under the LBH589 designation in clinical trials for various cancers, including renal cell carcinoma and Waldenstrom's macroglobulinemia.