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Nilotinib + LDE225

Phase 1

Philadelphia Chromosome Positive Chronic Myelogenous Leukemia | Small molecule | Oncology |Novartis AG|Last Updated: Dec 9, 2020

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
UNCONTROLLEDBiomarker
Total Trials1
Total Enrollment11
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01456676Nilotinib and LDE225 in the Treatment of Chronic or Accelerated Phase Myeloid Leukemia in Patients Who Developed Resistance to Prior TherapyPHASE1 COMPLETED 11Jan 1, 2012Feb 1, 2014Dec 9, 20207 Canada, France +3
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Study Endpoints
Primary Endpoints
Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy
56 days (2 treatment cycles at 28 days each)

Determination of the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of nilotinib in combination with LDE225

Secondary Endpoints
No of participants with Adverse drug reactions and serious adverse drug reactions, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and electrocardiograms
336 days (12 treatment cycles)
Plasma concentration and basic pharmacokinetics (PK) parameters (as Cmax, Tmax, AUC)
50 days
Major molecular response (MMR) rates at 3, 6 and 12 months
336 days (12 treatment cycles)
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Study Design & Arms
AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Nilotinib + LDE225EXPERIMENTALThe planned dose of nilotinib 400 mg b.i.d (twice a day) was selected for the combination as this is the dose approved for the treatment of the patient population that will be included in the present study. The starting dose for LDE225 chosen for the current study is 400 mg once daily(q.d.). The maximum dose of LDE225 that will be tested in combination with nilotinib is 800 mg once dail.y
Interventions
NameTypeDescription
Nilotinib + LDE225DRUGNilotinib is an aminopyrimidine ATP-competitive inhibitor of the protein tyrosine kinaseactivity of BCR-ABL.
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites7

Inclusion Criteria: 1. Philadelphia chromosome positive (Ph+) CML in chronic phase (CP) or accelerated phase (AP)with resistance to at least one prior BCR-ABL targeting TKI 2. Documented chronic phase CML 3. Adequate end organ function 4. Female patients of childbearing potential must have a negati...

Countries:CanadaFranceGermanyItalySpain
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