Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LGH447 · 4 trials · 3 indications
Estimate the maximum tolerated dose and/or recommended dose for expansion of LGH447 in Japanese patients
Using a Bayesian logistic regression model (BLRM) to guide dose escalation and predict MTD or determine the RP2D for LGH447 in combination with BYL719 in relapsed and refractory multiple myeloma. The frequency and characteristics of DLTs will be assessed.
The proportion of patients with a confirmed best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) as assessed by Investigators using the International Myeloma Working group (IMWG) Criteria with modifications. End of Study (defined as the time when all patients have completed at least 6 cycles of treatment or discontinued treatment, or have been lost to follow up, whichever occurs first.
Frequency and characteristics of dose limiting toxicities
Incidence rate of dose limiting toxicity
| Arm | Type | Description |
|---|---|---|
| LGH447 | EXPERIMENTAL | LGH447, QD |
| Phase Ib: LGH447 + BYL719 | EXPERIMENTAL | Dose-escalation, LGH447 in combinatinon with BYL719 |
| Phase II: LGH447 + BYL719 | EXPERIMENTAL | LGH447 + BYL719 (dosing according to MTD/RP2D from Phase Ib portion of the study) |
| Phase II: LGH447 alone | EXPERIMENTAL | LGH447 alone (dosing according to single-agent RDE) |
| LGH447 monotherapy arm | EXPERIMENTAL | LGH447 monotherapy in patients with AML or MDS |
| LGH447 + midostaurin combination arm | EXPERIMENTAL | LGH447 + midostaurin in patients with AML |
| LGH447 and midazolam | EXPERIMENTAL | Eligible patients will receive midazolam on two separate days, the first dose will be administered prior to the start of LGH447 and the second will be co-administered with LGH447. After that, the patients will continue to be treated with oral LGH447 until disease progression or occurrence of unacceptable toxicity. |
| Name | Type | Description |
|---|---|---|
| LGH447 | DRUG | LGH447, QD |
| BYL719 | DRUG | PI3K-alpha inhibitor |
| LGH447 + midostaurin | DRUG | LGH447 + midostaurin in patients with AML |
| midazolam | DRUG | - |
Inclusion Criteria: -Confirmed diagnosis of relapsed and/or refractory MM for which no standard effective treatment options exist. Exclusion Criteria: -Uncontrolled cardiovascular condition, including ongoing cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within t...
LGH447 is an investigational oral small molecule being studied in hematologic malignancies, specifically acute myeloid leukemia (AML), high risk myelodysplastic syndrome (MDS), and multiple myeloma, including relapsed and refractory multiple myeloma. It is in Phase 1 clinical development and is not approved for any indication.
LGH447 targets the PIM kinases PIM1, PIM2, and PIM3. It acts as an inhibitor of these proteins, which are involved in cell survival and proliferation signaling in hematologic cancers. Targeting all three PIM family members distinguishes it from agents selective for a single isoform.
LGH447 is being developed by Novartis AG, which trades under the ticker NVS. Novartis sponsored the Phase 1 clinical program evaluating the compound across multiple myeloma, acute myeloid leukemia, and high risk myelodysplastic syndrome.
LGH447 is in Phase 1 clinical development. It is an investigational agent and has not been approved by the FDA or any other regulatory authority. All four registered studies of LGH447 are Phase 1 trials, and all have completed.
Four Phase 1 trials of LGH447 have been registered: NCT02160951 in Japanese patients with relapsed or refractory hematologic malignancies, NCT02144038 combining LGH447 with BYL719 in relapsed and refractory multiple myeloma, NCT02078609 in AML or high risk MDS, and NCT01456689 in relapsed or refractory multiple myeloma. All are completed.
The LGH447 Phase 1 program enrolled 92 patients in total across its registered studies. The largest trial, NCT02078609 in acute myeloid leukemia and high risk myelodysplastic syndrome, enrolled 70 patients, while the multiple myeloma studies enrolled smaller cohorts.