To determine the MTD/RP2D of the HDM201 and LEE011 combination and evaluate whether the combination is safe and has beneficial effects in patients with liposarcoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
74
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Bordeaux, France
Novartis Investigative Site
Lyon, France
Novartis Investigative Site
Essen, Germany
Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment.
DLTs in the first cycle of treatment.
Time frame: 5 years
Phase Ib: Exposure to HDM201 and LEE011 as measured by AUC 0-24h
as measured by AUC0-24h
Time frame: 5 years
Phase II: Progression free survival (PFS)
To assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Time frame: 5 years
Phase Ib/II: Incidence and severity of AEs and SAEs
Run-in part to assess safety of HDM201 in combination with LEE011
Time frame: 5 years
Phase Ib/II: number of patients with dose interruptions and reduction
Run-in part To assess tolerability of HDM201 in combination with LEE011
Time frame: 5 years
Phase Ib/II: dose intensity
Run-in part To assess tolerability of HDM201 in combination with LEE011
Time frame: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Cmax
Run-in part to evaluate PK parameters of HDM201 and LEE011
Time frame: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: Tmax
Run-in part to evaluate the PK parameters of HDM201 and LEE011
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Novartis Investigative Site
Ulm, Germany
Novartis Investigative Site
Singapore, Singapore
Novartis Investigative Site
Barcelona, Catalonia, Spain
Novartis Investigative Site
Madrid, Spain
Novartis Investigative Site
Taipei, Taiwan
Time frame: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUClast
Run-in part to evaluate the PK parameters of HDM201 and LEE011
Time frame: 5 years
Phase Ib/II: Pharmacokinetics (PK) parameters of HDM201 and LEE011: AUCtau
Run-in part to evaluate the PK parameters of HDM201 and LEE011
Time frame: 5 years
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in blood (GDF-15)
Run-in part measure of GDF-15 fold-change in protein levels (PD direct targets of p53) to assess PD changes from baseline in blood and a potential relationship with clinical outcome.
Time frame: 5 years
Phase Ib/II: Changes from baseline of Pharmacodynamics (PD) markers in tumor tissue (p21, MDM2)
Run-in part measure of p21 and MDM2 protein levels by IHC (H-Score) (p53 and CDK4 pathways) to assess changes from baseline of PD markers in tumor tissue and a potential relationship with clinical outcome.
Time frame: 5 years
Phase Ib/II: anti-tumor activity endpoint (BOR, PFS)
Run-in part to assess PD effect of HDM201 and LEE011 and a potential relationship with clinical outcome
Time frame: 5 years
Phase Ib: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
Run-in part to assess the preliminary anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Time frame: 5 years
Phase II: BOR, ORR and PFS as per RECIST v1.1, assessed by investigator
Run-in part to further assess the anti-tumor activity of HDM201 in combination with LEE011 in liposarcoma
Time frame: 5 years