Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Panobinostat
LBH581 · 20 trials · 26 indications
Safety monitoring was conducted throughout the study.
Adverse events were collected from baseline up to 30 days post treatment at scheduled visits. Severity of adverse events was assessed according to the current version of Common Terminology Criteria for Adverse Events (CTCAE). If CTCAE grading did not exist for an adverse event, the severity of mild, moderate, severe, and life-threatening, corresponding to Grades 1 - 4, was used
The primary endpoint will be the best overall response rate (ORR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
The primary endpoint will be the best overall response rate (ORR)
Overall response rate=(PR+nCR+CR) CR= \< 5% plasma cells in bone marrow. No confirmation on bone marrow plasma cell (additional assessment) is needed to document CR except patients with non-secretory myeloma where the bone marrow examination must be repeated after an interval of at least 6 weeks, Absence of M-protein in serum and urine by immunofixation,nCR same as CR without out Absence of M-protein in serum and urine by immunofixation,PR+ 50% reduction of serum M-protein and sofft tissue Plasmacytomas all for more than 6 weeks.
Response to treatment was defined as complete remission rate (CRR). CRR is complete remission (CR) and morphologic CR with incomplete blood count recovery (residual neutropenia or thrombocytopenia) (CRi). To stop or to proceed with Stage 2 of a given stratum of the Simon's optimal 2-stage design was based on the number of patients with CR/CRi and a safety evaluation of the patients from Stage 1 in that stratum. If early results clearly indicated that the drug was not active or worthy of further investigation, enrollment of that particular stratum would be terminated. CR and CRi were assessed by the Investigator according to IWG response Criteria for AML (Cheson et al 2003). As per protocol we would continue to stage II if ≥ 4 patients out of 26 patients enrolled to stage I had a CR or a CRi. As per response observed there was only 1 patient with CR/CRi in stratum A and 2 patients with CR/CRi in Stratum B.
ORR was number of participants with best overall disease response of complete response(CR)/partial response(PR).Best overall disease response was best disease response recorded from start of treatment until disease progression/recurrence.CR=complete normalization of all index nodal,extranodal lesions,complete disappearance of all extranodal lesions.PR=50% decrease in SPD for up to 6 identified dominant lesions (splenic,hepatic nodules) from baseline.Stable=neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease (PD), reference smallest sum diameters while on study.Progression=50% increase in sum of longest diameter of all target lesions,from smallest sum of longest diameter of all target lesions recorded at or after baseline/a new lesion/progression of non-target lesions.Unknown is progression not documented,one/more of index lesions not assessed or have been assessed using a different method than baseline at the time of radiologic evaluation.
Objective response rate measured according to the RECIST (Response Evaluation Criteria In Solid Tumours).
The PFS rate was defined as the percentage of participants that were alive without documented disease progression at the end of 24 weeks from first study treatment. Disease Progression as per response evaluation criteria in solid tumors (RECIST) criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 centimeter (cm) at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of greater than or equal to (\>=) 2 unequivocal new lesions confirmed on a second scan at least 6 weeks later.
Skin response was primarily classified based on an assessment using mSWAT, provided there was documented evidence of stable disease or better in lymph node/viscera.The mSWAT is a tool specifically developed to evaluate the extent of skin disease in CTCL (Olsen et al 2007). Responses in the skin based on SWAT are defined as: * Complete Response (CR): no evidence of skin disease * Partial Response (PR): ≥ 50% decrease of the modified SWAT score compared with baseline * Stable Disease (SD): Neither CR, PR, or PD as compared with baseline, i.e. change from baseline is less than a 50% decrease but also less than a 25 % increase in the modified SWAT score * Progressive Disease (PD): ≥ 25% increase in the modified SWAT score compared with baseline.
DLT will be assessed during PK run-in period (up to 7 days) and 1st cycle (28 days)
To determine the DLTs and MTD of panobinostat given in combination with bortezomib.
Dose limiting toxicity (DLT) was defined as a toxicity requiring treatment withdrawal and included the following: Non-hematologic toxicity qualifying for DLT and Hematologic toxicity qualifying for DLT
Dose limiting toxicity (DLT) was defined as a toxicity requiring treatment withdrawal and included the following: Non-hematologic toxicity qualifying for DLT and Hematologic toxicity qualifying for DLT
Composite complete response is defined as complete response (CR), Complete response with incomplete blood count recovery (CRi) or bone marrow complete response (BM-CR) as defined by the International Working Group (IWG) response criteria.
| Arm | Type | Description |
|---|---|---|
| Panobinostat (PAN) | EXPERIMENTAL | Participants received 45 mg orally 3 times a week (TIW), every other week (QOW), |
| Placebo | PLACEBO_COMPARATOR | Participants received matching placebo to PAN TIW, QOW. |
| Panobinostat + Bortezomib + Dexamethasone | EXPERIMENTAL | - |
| Placebo + Bortezomib + Dexamethasone | PLACEBO_COMPARATOR | - |
| Panobinostat - 10 to 40 mg/day TIW QoW | EXPERIMENTAL | 10 to 40mg/day TIW QoW (3 times/week every other week) as per parent protocol design |
| Panobinostat, Lenalidomide and Dexamethasone | EXPERIMENTAL | All patients will receive oral panobinostat, lenalidomide and dexamethasone as per protocol. |
| panobinostat + bortezomib & dexamethasone | EXPERIMENTAL | panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma |
| Stratum A | EXPERIMENTAL | patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week. |
| Stratum B | EXPERIMENTAL | patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week. |
| Panobinostat | EXPERIMENTAL | Participants received panobinostat 40 mg, capsules, orally, thrice every week (i.e. days 1, 3 and 5), in each cycle of 21 days until unacceptable toxicity, disease progression, start of new anti-cancer therapy or withdrawal of consent (up to approximately 48 months). |
| Previously treated with oral bexarotene | EXPERIMENTAL | Participants received Panobinostat 20 milligrams per day (mg/day) capsule orally, once a day (OD) on 3 days per week. (Monday, Wednesday and Friday or alternative Day 1, 3 and 5). |
| No prior oral bexarotene treatment | EXPERIMENTAL | Participants received Panobinostat 20 milligrams per day (mg/day) capsule orally, once a day (OD) on 3 days per week. (Monday, Wednesday and Friday or alternative Day 1, 3 and 5). |
| Panobinostat and Azacitidine | EXPERIMENTAL | combination regimen |
| Cohort 1 | EXPERIMENTAL | Subjects will be treated with ruxolitinib 5 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
| Cohort 2 | EXPERIMENTAL | Subjects will be treated with ruxolitinib 10 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
| Cohort 3 | EXPERIMENTAL | Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
| Cohort 4 | EXPERIMENTAL | Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 15 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
| Cohort 5 | EXPERIMENTAL | Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 20 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
| Cohort 6/6+ | EXPERIMENTAL | Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 25 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
| Open Label Drug Therapy | EXPERIMENTAL | Single arm |
| LBH589 | EXPERIMENTAL | - |
| Panobinostat + 5-Azacytidine | EXPERIMENTAL | In phase I: Panobinostat : Escalating doses starting with 20 mg delivered orally at Day 3, Day 5, Day 8, Day 10, Day 12, Day 15. In phase II: Panobinostat : Rapid Phase II doses at 30 mg delivered orally at Day 3, Day 5, Day 8, Day 10, Day 12, Day 15. In both phases, dose of 5-Azacytidine was 75 mg/m\^2, subcutaneously Daily for Day 1 to Day 7. |
| 5-Azacytidine | ACTIVE_COMPARATOR | The dose of 5-Aza was fixed at 75 mg/m2/day for 7 days in Week 1 of each cycle. 5-Aza was sourced locally, except in 4 countries (Hungary, Switzerland, UK, and Spain, for which a central purchase was used by Novartis. Dose of 5-Azacytidine : 75 mg/m\^2 subcutaneously daily from Day 1 to Day 7. |
| Name | Type | Description |
|---|---|---|
| Panobinostat | DRUG | - |
| Placebo | DRUG | Placebo |
| Bortezomib | DRUG | Bortezomib was administered 2 x week ( 2weeks on 1 week off) |
| Dexamethasone | DRUG | Dexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration |
| Lenalidomide | DRUG | Each cycle is 28 days. Lenalidomide will be given 25 mg: Days 1-21. |
| Panobinostat/LBH589 | DRUG | - |
| LBH581 | DRUG | 25 mg/5 ml solution packaged in 6 ml type I glass vials and given as a 30 minutes infusion at the dose of 20 mg/m2 i.v., on day 1 and 8, every 21 days. |
| Cytarabine | DRUG | Induction - 100 mg/m2 continuous IV daily for 7 doses on day 3-9. Second induction - 100 mg/m2 continuous IV daily for 7 doses on day 3-7. Dosing for consolidation - 100 mg/m2 continuous IV daily for 7 doses on day 3-9. |
| Daunorubicin | DRUG | Induction - 60 mg/m2 IV over 15-30 minutes daily for 3 doses on day 3-5. Second induction - 60 mg/m2 IV over 15-30 minutes daily for 2 doses on day 3 and 4. Dosing for consolidation - 60 mg/m2 IV over 15-30 minutes daily for 3 doses on day 3-5. |
| ruxolitinib | DRUG | Given twice daily in 28-day cycles. |
| panobinostat (LBH589) | DRUG | - |
| 5-Azacytidine | DRUG | - |
| panobinostat/LBH589B | DRUG | - |
Inclusion Criteria: 1. Patient age is greater than or equal to 18 years 2. Patient has a history of histologically confirmed classical HL (i.e. Nodular sclerosing (NSHL), Mixed-cellularity (MCHL), Lymphocyte-rich (LRHL), Lymphocyte depleted (LDHL)) 3. Patient has achieved a complete response by CT/...
LBH581 is an investigational small molecule being studied for the treatment of small cell lung carcinoma, an aggressive form of lung cancer. It is in Phase 2 clinical development and is not approved for any indication. The only reported trial enrolled 21 adult patients with small cell lung cancer in Germany and Italy.
LBH581 is being developed by Novartis AG, which trades on the New York Stock Exchange under the ticker NVS. Novartis is the sponsor of the Phase 2 study of LBH581 in small cell lung carcinoma. No other developer or partner is associated with the asset.
LBH581 is in Phase 2 development. It has completed one Phase 2 trial in small cell lung carcinoma, and no active trials are currently listed. The program enrolled 21 patients in total. LBH581 is investigational and has not been approved by the FDA or any other regulatory agency.
LBH581 has been evaluated in one clinical trial, NCT01222936, titled LBH Phase II in Small Cell Lung Cancer (SCLC). The Phase 2 study enrolled 21 adults aged 18 and older of all sexes, took place in Germany and Italy, and is now completed. It was an uncontrolled, non-randomized, open-label study.
No. LBH581 is an investigational drug and has not been approved by the FDA for small cell lung cancer or any other indication. It remains in clinical development at the Phase 2 stage, with one completed trial in small cell lung carcinoma and no active studies reported.