Clinical Trials /

A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies

NCT03522142

Description:

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and early clinical activity of single-agent INCB081776 (Part 1) and INCB081776 in combination with INCMGA00012 (Part 2).

Related Conditions:
  • Acute Myeloid Leukemia
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies
  • Official Title: A Phase 1a/1b Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: INCB 81776-101
  • NCT ID: NCT03522142

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
INCB081776INCB081776
INCMGA00012retifanlimabINCB081776 + INCMGA00012

Purpose

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and early clinical activity of single-agent INCB081776 (Part 1) and INCB081776 in combination with INCMGA00012 (Part 2).

Trial Arms

NameTypeDescriptionInterventions
INCB081776ExperimentalSingle-agent INCB081776.
  • INCB081776
INCB081776 + INCMGA00012ExperimentalINCB081776 in combination with INCMGA00012.
  • INCB081776
  • INCMGA00012

Eligibility Criteria

        Inclusion Criteria:

        • Male and female participants at least 18 years of age with advanced malignancies who have
        received or been intolerant to standard therapy:

        Parts 1A and 2A:

          -  Histologically confirmed advanced or metastatic gastric or GEJ adenocarcinoma, HCC,
             melanoma, NSCLC, RCC, soft-tissue sarcoma, SCCHN (recurrent or metastatic), TNBC, or
             urothelial carcinoma. Additional tumor histologies, including MSI-H tumors, may be
             allowed with approval from the medical monitor.

          -  Measurable disease per RECIST v1.1.

        Parts 1B and 2B:

        • Histologic confirmation of the cohort-specific tumor types specified below: Cohort 1 -
        Advanced or metastatic melanoma Cohort 2 - Advanced or metastatic NSCLC Cohort 3 -
        Recurrent or metastatic SCCHN Cohort 4 - Advanced or metastatic soft-tissue sarcoma

          -  Cohorts 1-3 must have received 1 prior PD-1/L1 treatment and have experienced PD
             during or after that treatment and have progressed on other SOC therapy(ies); Cohort 4
             must be PD-1/L1 treatment naïve but have progressed on SOC therapy(ies).

          -  Measurable disease per RECIST v1.1.

          -  Must be willing to submit to a fresh baseline tumor biopsy and an on-treatment biopsy
             between Cycle 2 Day 1 and Cycle 3 Day 1.

          -  Care should be taken to biopsy the same lesion for the baseline and on-treatment
             samples. If a participant has a solitary target lesion, this should not be biopsied.

        Part 1C:

          -  Participants with relapsed/refractory AML following standard therapy; acute
             promyelocytic leukemia (M3) and therapy-related AML are excluded.

          -  FLT3-ITD and IDH1/2 wild-type or mutated are eligible; appropriate targeted therapy
             for participants with actionable mutations must have been received.

        Exclusion Criteria:

          -  Laboratory values not within the protocol-defined range.

          -  History of retinal disease as defined in the protocol.

          -  Clinically significant cardiac disease as per protocol-defined criteria.

          -  History or presence of an ECG that, in the investigator's opinion, is clinically
             meaningful as per protocol-defined criteria.

          -  Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases
             that have progressed as per protocol-defined criteria.

          -  Active or inactive autoimmune disease or syndrome that has required systemic treatment
             in the past 2 years or receiving systemic therapy for an autoimmune or inflammatory
             disease.

          -  Prior Grade 3 or higher immune-related AEs or any ocular toxicity on prior
             immunotherapy as per protocol-defined criteria.

          -  Receipt of any vitamin K antagonists, systemic corticosteroids, live vaccines, or
             treatment with any anticancer medications or investigational drugs within the
             protocol-defined intervals.

          -  Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy and/or
             complications from prior surgical intervention before starting study treatment.

          -  Active infection requiring systemic therapy.

          -  Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.

          -  Known history of HIV (HIV 1/2 antibodies).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1 and Part 2: Number of treatment-emergent adverse events (TEAEs)
Time Frame:Screening through 90 days after end of treatment, up to approximately 1 year.
Safety Issue:
Description:A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.

Secondary Outcome Measures

Measure:Part 1 and Part 2: Cmax of INCB081776
Time Frame:Up to approximately 3 weeks.
Safety Issue:
Description:Maximum observed plasma concentration.
Measure:Part 1 and Part 2: Tmax of INCB081776
Time Frame:Up to approximately 3 weeks.
Safety Issue:
Description:Time to maximum plasma concentration.
Measure:Part 1 and Part 2: t½ of INCB081776
Time Frame:Up to approximately 3 weeks.
Safety Issue:
Description:Apparent plasma terminal phase disposition half-life
Measure:Part 1 and Part 2: Pharmacokinetic/ pharmacodynamic correlation
Time Frame:Up to approximately 3 weeks.
Safety Issue:
Description:To evaluate the correlation pharmacokinetic and pharmacodynamics of INCB081176
Measure:Part 1 and Part 2: Overall response rate
Time Frame:Up to approximately 1 year.
Safety Issue:
Description:Defined as the percentage of participants having complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Measure:Part 1 and Part 2: Disease control rate
Time Frame:Up to approximately 1 year.
Safety Issue:
Description:Defined as the percentage of participants having CR, PR, or stable disease (SD) per RECIST v1.1.
Measure:Part 1 and Part 2: Duration of response
Time Frame:Up to approximately 1 year.
Safety Issue:
Description:Defined as the time from earliest date of disease response until the earliest date of disease progression (per RECIST v1.1) or death due to any cause, if occurring sooner than progression.
Measure:Part 1 and Part 2: AUC0-t of INCB081776
Time Frame:Up to approximately 3 weeks.
Safety Issue:
Description:Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration
Measure:Part 1 and Part 2: Cmin of INCB081776
Time Frame:Up to approximately 3 weeks.
Safety Issue:
Description:Trough concentration of INCB081776
Measure:Part 1 and Part 2: AUC0-∞ of INCB081776
Time Frame:Up to approximately 3 weeks.
Safety Issue:
Description:Area under the single-dose plasma concentration-time curve from Hour 0 to infinity
Measure:Part 1 and Part 2 : CL/F of INCB081776
Time Frame:Up to approximately 3 weeks.
Safety Issue:
Description:Oral dose clearance
Measure:Part 1 and Part 2 : λz of INCB081776
Time Frame:Up to approximately 3 weeks.
Safety Issue:
Description:Terminal elimination rate constant
Measure:Part 1 and Part 2 : Vz/F of INCB081776
Time Frame:Up to approximately 3 weeks.
Safety Issue:
Description:Apparent oral dose volume of distribution

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • Advanced solid tumors
  • AXL
  • MER
  • AXL/MER
  • PD-1

Last Updated

October 6, 2020