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LGH447

Phase 1

AML and High Risk MDS | Small molecule | Oncology |Novartis AG|Last Updated: Dec 17, 2020

Success Probability

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Market & Valuation

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Trial Design

CONTROLLED
Total Trials1
Total Enrollment70

FDA Designations

No designations recorded

Clinical trial landscape

LGH447 · 4 trials · 3 indications

Phase 1 4
NCT02160951Dose Escalation Study of LGH447 in Japanese Patients With Relapsed and/or Refractory Hematologic MalignanciesMultiple Myeloma
COMPLETED13 Analytics
NCT02144038Study of the Safety and Effectiveness of LGH447 and BYL719 in Patients With Relapsed and Refractory Multiple MyelomaRelapsed and Refractory Multiple Myeloma
COMPLETED20 Analytics
NCT02078609A Safety and Efficacy Study of LGH447 in Patients With Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)AML and High Risk MDS
COMPLETED70 Analytics
NCT01456689A Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple MyelomaMultiple Myeloma
COMPLETED79 Analytics
PHASE1COMPLETED
Dose Escalation Study of LGH447 in Japanese Patients With Relapsed and/or Refractory Hematologic Malignancies
Multiple MyelomaUnlock trial analytics
PHASE1COMPLETED
Study of the Safety and Effectiveness of LGH447 and BYL719 in Patients With Relapsed and Refractory Multiple Myeloma
Relapsed and Refractory Multiple MyelomaUnlock trial analytics
PHASE1COMPLETED
A Safety and Efficacy Study of LGH447 in Patients With Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)
AML and High Risk MDSUnlock trial analytics
PHASE1COMPLETED
A Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma
Multiple MyelomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Incidence rate of dose limiting toxicities
28 days

Estimate the maximum tolerated dose and/or recommended dose for expansion of LGH447 in Japanese patients

Phase Ib: Number of Total Dose-limiting Toxicities (DLT)
Cycle 1 (28 days)

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.

Phase II: Overall Response Rate (ORR) as assessed by Investigators
29 months (End of Study)

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.

Incidence rate of dose limiting toxicities (DLTs) of LGH447 monotherapy arm in patients with AML or MDS and of LGH447 + midostaurin in patients with AML
28 days post study treatment

Frequency and characteristics of dose limiting toxicities

Estimate the MTD and/or RDE
12 months

Incidence rate of dose limiting toxicity

Secondary Endpoints

Number of patients with adverse events as a measure of safety and tolerability of LGH447
28 days and till the end of the study, an average of 84 days
Pharmacokinetics profile of LGH447 and its metabolites if appropriate
Baseline, 0.5, 1, 2, 3, 4, 5, 6, 8, 24 hours on Cycle1Day1, 14 and 28 and baseline on Cycle2Day14 and Cycle3Day1
Overall Response Rate
Every 28 days till the end of the study, an average of 84 days
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
LGH447EXPERIMENTALLGH447, QD
Phase Ib: LGH447 + BYL719EXPERIMENTALDose-escalation, LGH447 in combinatinon with BYL719
Phase II: LGH447 + BYL719EXPERIMENTALLGH447 + BYL719 (dosing according to MTD/RP2D from Phase Ib portion of the study)
Phase II: LGH447 aloneEXPERIMENTALLGH447 alone (dosing according to single-agent RDE)
LGH447 monotherapy armEXPERIMENTALLGH447 monotherapy in patients with AML or MDS
LGH447 + midostaurin combination armEXPERIMENTALLGH447 + midostaurin in patients with AML
LGH447 and midazolamEXPERIMENTALEligible 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.

Interventions

NameTypeDescription
LGH447DRUGLGH447, QD
BYL719DRUGPI3K-alpha inhibitor
LGH447 + midostaurinDRUGLGH447 + midostaurin in patients with AML
midazolamDRUG -
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites4

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...

Countries:JapanUnited StatesAustraliaGermanyItalySingaporeFranceNetherlandsSpain
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Frequently asked questions about LGH447

What is LGH447 used for?

LGH447 is an investigational small molecule being studied for the treatment of multiple myeloma, relapsed and refractory multiple myeloma, acute myeloid leukemia (AML), and high risk myelodysplastic syndrome (MDS). It is an oral therapy developed by Novartis AG for patients with these hematologic malignancies.

Who makes LGH447?

LGH447 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 oral small molecule in Phase 1 clinical development for multiple myeloma, AML, and high risk MDS.

What phase is LGH447 in?

LGH447 is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities. All four clinical trials for LGH447 are Phase 1 studies that have been completed, with a total enrollment of 92 patients across the trials.

What clinical trials is LGH447 in?

LGH447 has been studied in four completed Phase 1 trials. NCT01456689 evaluated LGH447 in relapsed and/or refractory multiple myeloma with 79 patients. NCT02078609 studied it in AML and high risk MDS with 70 patients. NCT02144038 tested LGH447 combined with BYL719 in relapsed and refractory multiple myeloma with 20 patients. NCT02160951 was a dose escalation study in Japanese patients with hematologic malignancies.

Is LGH447 the same as BYL719?

No, LGH447 is not the same as BYL719. They are distinct investigational drugs that have been studied together in a combination trial for relapsed and refractory multiple myeloma. The trial NCT02144038 evaluated the safety and effectiveness of LGH447 and BYL719 when used together in patients with this condition.