Clinical Trials /

INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors

NCT04580485

Description:

This is a multicenter, open-label, dose-escalation/dose-expansion Phase 1 clinical study to investigate the safety, tolerability, PK profile, pharmacodynamics, and preliminary clinical efficacy of INCB106385 when given as monotherapy or in combination with INCMGA00012 in participants with selected CD8 T-cell-positive advanced solid tumors including SCCHN, NSCLC, ovarian cancer, CRPC, TNBC, or bladder cancer

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors
  • Official Title: A Phase 1, Open-Label, Multicenter Study of INCB106385 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: INCB 106385-102
  • NCT ID: NCT04580485

Conditions

  • Ovarian Cancer
  • Bladder Cancer
  • Non Small Cell Lung Cancer
  • Squamous Cell Carcinoma of Head and Neck
  • Triple Negative Breast Cancer
  • Castration Resistant Prostate Cancer

Interventions

DrugSynonymsArms
INCB106385Treatment Group A (TGA) - INCB106385
INCMGA00012Treatment Group B (TGB) - INCB106385+INCMGA00012

Purpose

This is a multicenter, open-label, dose-escalation/dose-expansion Phase 1 clinical study to investigate the safety, tolerability, PK profile, pharmacodynamics, and preliminary clinical efficacy of INCB106385 when given as monotherapy or in combination with INCMGA00012 in participants with selected CD8 T-cell-positive advanced solid tumors including SCCHN, NSCLC, ovarian cancer, CRPC, TNBC, or bladder cancer

Trial Arms

NameTypeDescriptionInterventions
Treatment Group A (TGA) - INCB106385ExperimentalIn part 1 dose escalation, the dose levels will be escalated following a BOIN design. In part 2 dose expansion, participants will be assigned to different groups based on their tumor types and treated at the RDE.
  • INCB106385
Treatment Group B (TGB) - INCB106385+INCMGA00012ExperimentalIn part 1 dose escalation, the dose levels will be escalated following a BOIN design. In part 2 dose expansion, participants will be assigned to different groups based on their tumor types and treated at the RDE.
  • INCB106385
  • INCMGA00012

Eligibility Criteria

        Inclusion Criteria:

          -  Ability to comprehend and willingness to sign an ICF.

          -  Willing and able to conform to and comply with all Protocol requirements.

          -  Histologically or cytologically confirmed advanced/metastatic SCCHN, NSCLC, ovarian
             cancer, TNBC, CRPC or bladder cancer that progressed after treatment with available
             therapies (including anti PD-(L)1 therapy (if applicable).

          -  Willingness to undergo pre- and on-treatment tumor biopsy.

          -  Have CD8 T-cell-positive tumors.

          -  Presence of measurable disease according to RECIST v1.1.

          -  ECOG performance status 0 to 1.

          -  Life expectancy > 12 weeks.

          -  Willingness to avoid pregnancy or fathering children based.

          -  Acceptable laboratory parameters

        Exclusion Criteria:

          -  Clinically significant cardiac disease.

          -  Known or active CNS metastases and/or carcinomatous meningitis.

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

          -  Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses
             > 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive
             therapy within 7 days before the first dose of study treatment.

          -  Known additional malignancy that is progressing or requires active treatment,or
             history of other malignancy within 2 years of the first dose of study treatment.

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

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

          -  Immune-related toxicity during prior immune therapy for which permanent
             discontinuation of therapy is recommended, or any immune-related toxicity requiring
             intensive or prolonged immunosuppression to manage.

          -  Any prior chemotherapy, biological therapy, or targeted therapy to treat the
             participant's disease within 5 half-lives or 28 days (whichever is shorter) before the
             first dose of study treatment.

          -  Any prior radiation therapy within 28 days before the first dose of study treatment.

          -  Undergoing treatment with another investigational medication or having been treated
             with an investigational medication within 5 half-lives or 28 days (whichever is
             shorter) before the first dose of study treatment.

          -  Concomitant treatment with strong CYP3A4 inhibitors or inducers.

          -  Receipt of a live vaccine within 30 days of the first dose of study treatment.

          -  Infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week
             of the first dose of study treatment.

          -  Evidence of HBV or HCV infection or risk of reactivation.

          -  Known history of HIV (HIV 1/2 antibodies).

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

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

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

          -  Is pregnant or breastfeeding or expecting to conceive or father children within the
             projected duration of the study.

          -  Any condition that would, in the investigator's judgment, interfere with full
             participation in the study,pose a significant risk to the participant; or interfere
             with interpretation of study data
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of treatment-emergent adverse events (TEAE)
Time Frame:Up to Approximately 28 months
Safety Issue:
Description:Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 90 days after last dose of study drug.

Secondary Outcome Measures

Measure:Cmax of INCB106385 as a single agent or in combination with INCMGA00012
Time Frame:Up to 6 months
Safety Issue:
Description:Maximum observed plasma concentration.
Measure:Tmax of INCB106385 as a single agent or in combination with INCMGA00012
Time Frame:Up to 6 months
Safety Issue:
Description:Time to maximum plasma concentration
Measure:Cmin of INCB106385 as a single agent or in combination with INCMGA00012
Time Frame:Up to 6 months
Safety Issue:
Description:Minimum observed plasma concentration over the dose interval
Measure:AUC of INCB106385 as a single agent or in combination with INCMGA00012
Time Frame:Up to 6 months
Safety Issue:
Description:Area under the plasma concentration-time curve
Measure:CL/F of INCB106385 as a single agent or in combination with INCMGA00012
Time Frame:Up to 6 months
Safety Issue:
Description:Apparent oral dose clearance
Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:Defined as the percentage of participants with a best overall response of CR or PR, as determined by investigator radiographic disease assessment according to RECIST v1.1.
Measure:Disease Control Rate
Time Frame:Up to approximately 24 months
Safety Issue:
Description:Defined as the percentage of participants with a best overall response of CR, PR, or SD, as determined by investigator radiographic disease assessment according to RECIST v1.1.
Measure:Duration Of Response (DOR)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:Defined as the time from the earliest date of CR or PR until the earliest date of disease progression, as determined by investigator radiographic disease assessment according to RECIST v1.1, or death due to any cause if occurring sooner than progression.
Measure:Change in tumoral gene expression
Time Frame:Predose and Week 5-6
Safety Issue:
Description:Defined as the percent of patients with change in tumoral targeted gene expression compared to baseline
Measure:Change in immune cell activation in tumors
Time Frame:Predose and Week 5-6
Safety Issue:
Description:Defined as the percent of patients demonstrating change in immune cell activation in tumors compared to baseline

Details

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

Trial Keywords

  • INCB106385
  • Advanced Solid Tumors
  • PD-1

Last Updated

January 6, 2021