Clinical Trials /

To Assess the Safety, Tolerability and Pharmacokinetics of INCB086550

NCT04674748

Description:

This study will assess the safety, tolerability, and PK of INCB086550 and determine the Maximum Tolerated Dose (MTD) and/or recommended Phase 2 Dose(RP2D) of INCB086550, whichever is lower, in Japanese participants with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: To Assess the Safety, Tolerability and Pharmacokinetics of INCB086550
  • Official Title: A Phase 1 Study Exploring the Safety, Tolerability, and Pharmacokinetics of INCB086550 in Japanese Participants With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: INCB86550-104
  • NCT ID: NCT04674748

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
INCB086550Dose Escalation of INCB086550

Purpose

This study will assess the safety, tolerability, and PK of INCB086550 and determine the Maximum Tolerated Dose (MTD) and/or recommended Phase 2 Dose(RP2D) of INCB086550, whichever is lower, in Japanese participants with advanced solid tumors.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation of INCB086550ExperimentalIn this study 3 dose levels will be evaluated to determine the MTD or RP2D (Decided by SMC according to the safety and PK data)
  • INCB086550

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to conform to and comply with all Protocol requirements, including
             all scheduled visits, Protocol procedures, and the ability to swallow oral medication.

               -  Histologically or cytologically confirmed diagnosis of any locally advanced or
                  metastatic solid tumors with measurable lesions per RECIST v1.1 not amenable to
                  local or other curative therapy.

               -  Disease progression after treatment with available therapies that are known to
                  confer clinical benefit or intolerant to or ineligible for standard treatment.

               -  ECOG performance status of 0 or 1.

               -  Life expectancy > 12 weeks.

               -  Female participants should agree to use medically acceptable contraceptive
                  measures should not be breastfeeding, and must have a negative pregnancy test
                  before the start of study drug administration if of childbearing potential.

               -  Female participants of childbearing potential must understand and accept that
                  pregnancy must be avoided during participation in the study, from screening
                  through 90 days after the last dose of study drug.

        Male participants should avoid unprotected sex with women of childbearing potential during
        the study and for a washout period of 90 days after the last dose of study drug.

          -  For participants who will be enrolled in the study and receive the RP2D of INCB086550
             in the expanded cohort: Willingness to undergo a tumor biopsy to obtain tumor tissue.
             Pretreatment and on-treatment tumor biopsies are required.

        Exclusion Criteria:

          -  Laboratory values not within the Protocol-defined range.

          -  Clinically significant cardiac disease, including left ventricular ejection fraction <
             40%, unstable angina, acute myocardial infarction within 6 months of Cycle 1 Day 1,
             New York Heart Association Class III or IV congestive heart failure, and arrhythmia
             requiring therapy.

          -  History or presence of abnormal ECG that, in the investigator's opinion, is clinically
             meaningful.

          -  Untreated brain or CNS metastases or brain or CNS metastases that have progressed (eg,
             evidence of new or enlarging brain metastasis or new neurologic symptoms attributable
             to brain or CNS metastases).

          -  Active or inactive autoimmune disease or syndrome (eg, rheumatoid arthritis, moderate
             or severe psoriasis, multiple sclerosis, inflammatory bowel disease) that has required
             systemic treatment in the past 2 years or receiving systemic therapy for an autoimmune
             or inflammatory disease (ie, with use of disease-modifying agents, corticosteroids, or
             immunosuppressive drugs).

          -  Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (doses
             exceeding 10 mg daily of prednisolone equivalent) or any other form of
             immunosuppressive therapy within 7 days before the first dose of study drug. Use of
             short courses of steroids for procedure prophylaxis, inhaled or topical steroids, or
             systemic corticosteroids ≤ 10 mg is permitted.

          -  Known additional malignancy that is progressing or requires active treatment.

          -  Evidence or a history of interstitial lung disease or active, noninfectious
             pneumonitis.

          -  Treatment with anticancer medications or investigational drugs is prohibited within
             the following intervals before the first administration of study drug.

          -  Concomitant treatment with moderate and potent CYP3A4/CYP3A5 inhibitors or inducers.

          -  Receipt of a live vaccine within 3 months of the first dose of study drug.

          -  Active infection requiring systemic therapy.

          -  Systemic antibiotic therapy. A washout of 28 days is required before the first dose of
             INCB086550.

          -  Probiotic supplement usage during screening and throughout the study treatment period.

          -  Known active HBV or HCV infection or risk of reactivation of HBV or HCV.

          -  History of organ transplant, including allogeneic stem cell transplantation.

          -  Known hypersensitivity or severe reaction to any component of study drug or
             formulation components.

          -  Inability to swallow food or any condition of the upper gastrointestinal tract that
             precludes administration of oral medications.

          -  Any condition that would, in the investigator's judgment, interfere with full
             participation in the study, including administration of study drug and attending
             required study visits; pose a significant risk to the participant; or interfere with
             interpretation of study data.

          -  Inability or unlikeliness of the participant to comply with the dose schedule and
             study evaluations, in the opinion of the investigator.

          -  Inadequate recovery from toxicity and/or complications from a major surgery before
             starting therapy.

          -  Women who are pregnant or breastfeeding.

          -  Inability of the participant (or parent, guardian, or legally authorized
             representative) to comprehend the ICF or unwillingness to sign the ICF.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Treatment Emergent Adverse Events (TEAE)
Time Frame:Up to 27 months
Safety Issue:
Description:Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:Up to 2 years
Safety Issue:
Description:Defined as the percentage of participants with best overall response of CR or PR as determined by the investigator per RECIST v1.1.
Measure:Cmax
Time Frame:Pre dose,Post dose on Cycle 1 Day 1 & Day 15, Pre dose on Cycle 1 Day 8, Cylce 2 Day 21, and Cycle 3 Day 1 (each cycle 28 days)
Safety Issue:
Description:Maximum Observed Plasma concentration of INCB086550
Measure:Tmax
Time Frame:Pre dose,Post dose on Cycle 1 Day 1 & Day 15, Pre dose on Cycle 1 Day 8, Cylce 2 Day 21, and Cycle 3 Day 1 (each cycle 28 days)
Safety Issue:
Description:Time to reach maximum (peak) Plasma concentration of INCB086550
Measure:Cmin
Time Frame:Pre dose,Post dose on Cycle 1 Day 1 & Day 15, Pre dose on Cycle 1 Day 8, Cylce 2 Day 21, and Cycle 3 Day 1 (each cycle 28 days)
Safety Issue:
Description:Trough plasma concentration of INCB086550
Measure:AUC0-t
Time Frame:Pre dose,Post dose on Cycle 1 Day 1 & Day 15, Pre dose on Cycle 1 Day 8, Cylce 2 Day 21, and Cycle 3 Day 1 (each cycle 28 days)
Safety Issue:
Description:Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration of INCB086550
Measure:AUC0-∞
Time Frame:Pre dose,Post dose on Cycle 1 Day 1 & Day 15, Pre dose on Cycle 1 Day 8, Cylce 2 Day 21, and Cycle 3 Day 1 (each cycle 28 days)
Safety Issue:
Description:area under the single-dose plasma concentration-time curve from Hour 0 to infinity of INCB086550
Measure:AUC(0-τ)
Time Frame:Pre dose,Post dose on Cycle 1 Day 1 & Day 15, Pre dose on Cycle 1 Day 8, Cylce 2 Day 21, and Cycle 3 Day 1 (each cycle 28 days)
Safety Issue:
Description:AUC to the end of dosing period of INCB086550
Measure:t1/2
Time Frame:Pre dose,Post dose on Cycle 1 Day 1 & Day 15, Pre dose on Cycle 1 Day 8, Cylce 2 Day 21, and Cycle 3 Day 1 (each cycle 28 days)
Safety Issue:
Description:Terminal half-life of INCB086550
Measure:CL/F
Time Frame:Pre dose,Post dose on Cycle 1 Day 1 & Day 15, Pre dose on Cycle 1 Day 8, Cylce 2 Day 21, and Cycle 3 Day 1 (each cycle 28 days)
Safety Issue:
Description:Oral dose clearance of INCB086550
Measure:λz
Time Frame:Pre dose,Post dose on Cycle 1 Day 1 & Day 15, Pre dose on Cycle 1 Day 8, Cylce 2 Day 21, and Cycle 3 Day 1 (each cycle 28 days)
Safety Issue:
Description:Terminal elimination rate constant of INCB086550
Measure:Vz/F
Time Frame:Pre dose,Post dose on Cycle 1 Day 1 & Day 15, Pre dose on Cycle 1 Day 8, Cylce 2 Day 21, and Cycle 3 Day 1 (each cycle 28 days)
Safety Issue:
Description:Apparent oral dose volume of distribution of INCB086550

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Biosciences Japan GK

Trial Keywords

  • Advanced
  • Metastatic
  • Refractory
  • Relapsed

Last Updated

January 12, 2021