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PKC412

Phase 1

Acute Myeloid Leukemia | Small molecule | Oncology |Novartis AG|Last Updated: Aug 11, 2017

Target and mechanism

Molecular targetFLT3
Target classGene
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedCONTROLLED
Total Trials1
Total Enrollment144

FDA Designations

No designations recorded

Clinical trial landscape

PKC412 · 1 trial · 2 indications

Phase 1 1
NCT00045942PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinase 3 (FLT3) (CPKC412A2104E1 and CPKC412A2104E2)Acute Myeloid Leukemia
COMPLETED144 Analytics
PHASE1COMPLETED
PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinase 3 (FLT3) (CPKC412A2104E1 and CPKC412A2104E2)
Acute Myeloid LeukemiaUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants With Best Clinical Response (Core)
from date of first patient first visit (FPFV), 29-Jan-2002, to date of last participant last visit (LPLV), 04-Sep-2003

Best clinical response was defined as complete response (CR) or partial response (PR), according to NCI definitions for AML and the guidelines for defining responses in MDS.

Percent Decrease in Phospho-FLT3 Compared to Baseline (Core)
days 1, 28
Number of Participants With Overall Clinical Response (E1)
from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004

Overall clinical response was defined as CR, PR, minor response (MR) or blast response (BR). CR and PR was defined according to NCI definitions, and MR and BR was defined according to the guidelines for defining hematologic improvement in MDS.

Percent Decrease in Phospho-FLT3 Compared to Baseline (E1)
days 1, 28
Percent Decrease in Phospho-FLT3 Compared to Baseline (E2)
Days 1, 28
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for PKC412 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for pharmacokinetic (PK) analysis.

Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for PKC412 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for pharmacokinetic (PK) analysis.

Time to Reach the Maximum Concentration After Drug Administration (Tmax) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for PK analysis.

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for PK analysis.

Terminal Elimination Half-life (T1/2) for PKC412 in the PKC + Itrconazole Combination Arm (E2)
Cycle 1: days 21 and 22

Blood samples were collected for PK analysis.

Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP62221 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for pharmacokinetic (PK) analysis.

Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP62221 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for pharmacokinetic (PK) analysis.

Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP62221 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for PK analysis.

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP622221 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for PK analysis.

Terminal Elimination Half-life (T1/2) for CGP62221 in the PKC + Itrconazole Combination Arm (E2)
Cycle 1: day 22,

Blood samples were collected for PK analysis.

Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP52421 Plasma in the PKC + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for pharmacokinetic (PK) analysis.

Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP52421 in the PKC + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for pharmacokinetic (PK) analysis.

Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for PK analysis.

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Cycle 1: days 21, 22, 28

Blood samples were collected for PK analysis.

Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15

Blood samples were collected for analysis.

Summary of CGP62221 Concentration (E2)
Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15

Blood samples were collected for analysis.

Summary of CGP52421 Concentration (E2)
Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15

Blood samples were collected for analysis.

Secondary Endpoints

Time to Disease Progression (TTP) (Core)
from date of FPFV, 29-Jan-2002, to date of LPLV, 04-Sep-2003
Summary of Midostaurin Plasma Concentration (Core)
Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1,
Summary of CGP62221 Plasma Concentration (Core)
Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1,
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PKC412 (Core)EXPERIMENTALParticipants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 mutated PKC412 100 mg/day (E1)EXPERIMENTALParticipants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 mutated PKC412 200 mg/day (E1)EXPERIMENTALParticipants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 wild type PKC412 100 mg/day (E1)EXPERIMENTALParticipants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 wild type PKC412 200 mg/day (E1)EXPERIMENTALParticipants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 mutated PKC412 dose escalationEXPERIMENTALParticipants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
FLT3 mutated PKC+Itraconazole (E2)EXPERIMENTALWithin a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
FLT3 wild type PKC412 dose escalation (E2)EXPERIMENTALParticipants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
FLT3 wild type PKC+Itraconazole (E2)EXPERIMENTALWithin a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.

Interventions

NameTypeDescription
ItraconazoleDRUGItraconazole was commercially available.
PKC412DRUGPKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.
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Eligibility Criteria

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

Inclusion criteria: 1. Patients: with AML who are not candidates for myelosuppressive chemotherapy or with AML who have relapsed disease or are refractory to standard therapy and not likely to require cytoreductive therapy within one month or with MDS subtypes refractory anemia with excess blas...

Countries:United States
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Frequently asked questions about PKC412

What is PKC412 used for in Acute Myeloid Leukemia?

PKC412 is an investigational small molecule being studied for the treatment of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes. It is a targeted therapy that has been evaluated in a Phase 1 clinical trial in the United States. The drug is still in clinical development and is not yet approved.

What does PKC412 target?

PKC412 targets FLT3, a gene that encodes the FMS-like tyrosine kinase 3 receptor. This receptor is involved in cell growth and division, and mutations in FLT3 are common in Acute Myeloid Leukemia. By targeting FLT3, PKC412 aims to inhibit the signaling pathways that drive leukemia cell proliferation.

Who makes PKC412?

PKC412 is being developed by Novartis AG, a multinational pharmaceutical company traded on the New York Stock Exchange under the ticker symbol NVS. Novartis is responsible for the clinical development and manufacturing of this investigational drug for Acute Myeloid Leukemia and Myelodysplastic Syndromes.

What phase is PKC412 in?

PKC412 is in Phase 1 clinical development. It has completed one Phase 1 trial (NCT00045942) that enrolled 144 participants with Acute Myeloid Leukemia or Myelodysplastic Syndromes. The drug is investigational and has not received FDA approval.

What clinical trials is PKC412 in?

PKC412 has been studied in one completed Phase 1 clinical trial, NCT00045942. This trial evaluated the drug in 144 participants with Acute Myeloid Leukemia or Myelodysplastic Syndromes, including those with wild-type or mutated FLT3. The trial was conducted in the United States and enrolled adults aged 18 years and older.