Clinical Trials /

IK-175 in Patients With Advanced or Metastatic Solid Tumors and Urothelial Carcinoma

NCT04200963

Description:

This study will be conducted in adult subjects diagnosed with any form of an advanced or metastatic solid tumors including urothelial carcinoma for which standard therapy is no longer effective or is intolerable. This is a phase 1, multi-center, open label study designed to assess safety and tolerability of IK-175, to determine the recommended phase 2 dose (RP2D). Disease response, pharmacokinetics (PK), pharmacodynamics, and response biomarkers will also be assessed.

Related Conditions:
  • Malignant Solid Tumor
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: KYN-175 in Patients With Advanced or Metastatic Solid Tumors and Urothelial Carcinoma
  • Official Title: A Phase 1, Open-Label, Dose-Escalation and Expansion Study of KYN-175, an Oral Aryl Hydrocarbon Receptor (AHR) Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors and Urothelial Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: KYN175-001
  • SECONDARY ID: IK-175
  • NCT ID: NCT04200963

Conditions

  • Urothelial Carcinoma
  • Urothelial Carcinoma Bladder
  • Bladder Cancer
  • Bladder Disease
  • Solid Tumor
  • Solid Carcinoma
  • Solid Tumor, Adult
  • Metastatic Cancer
  • Advanced Solid Tumor
  • Advanced Cancer
  • Metastatic Bladder Cancer
  • Metastatic Urothelial Carcinoma
  • Locally Advanced Solid Tumor
  • Neoplasms
  • Neoplasm Metastasis
  • Neoplasm Malignant
  • Neoplasm, Bladder
  • Urothelial Neoplasm
  • Neoplasm, Urinary Bladder
  • Bladder Neoplasm
  • Bladder Urothelial Carcinoma

Interventions

DrugSynonymsArms
KYN-175IK-175KYN-175 Dose Escalation

Purpose

This study will be conducted in adult subjects diagnosed with any form of an advanced or metastatic solid tumors including urothelial carcinoma for which standard therapy is no longer effective or is intolerable. This is a phase 1, multi-center, open label study designed to assess safety and tolerability of KYN-175, to determine the recommended phase 2 dose (RP2D). Disease response, pharmacokinetics (PK), pharmacodynamics, and response biomarkers will also be assessed.

Trial Arms

NameTypeDescriptionInterventions
KYN-175 Dose EscalationExperimentalApproximately 5 dose escalation steps are planned during the dose escalation phase of the study.
  • KYN-175
KYN-175 Dose ExpansionExperimentalA dose expansion phase will be performed in patients with KYN-175 after completion of the dose escalation to confirm the RP2D.
  • KYN-175

Eligibility Criteria

        Inclusion Criteria:

          -  Male and female adult patients 18 years of age or older on day of signing informed
             consent.

          -  Patients with confirmed solid tumors who have locally recurrent or metastatic disease
             that has progressed on or following all standard of care therapies or who is not a
             candidate for standard treatment.

          -  For patients with urothelial carcinoma, patients must have confirmation of urothelial
             carcinoma and have locally recurrent or metastatic disease that has progressed on or
             following all standard of care therapies, or who is not a candidate for standard
             treatment.

          -  Accessible tumor that can be safely accessed for multiple core biopsies and patient is
             willing to provide tissue from newly obtain biopsies before and during treatment.

          -  Have measurable disease.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          -  Adequate organ function.

          -  Highly effective birth control.

        Exclusion Criteria:

          -  Clinically unstable central nervous system (CNS) tumors or brain metastasis

          -  Patients who have not recovered to ≤ Grade 1 or baseline from all adverse events (AEs)
             due to previous therapies

          -  Any condition requiring continuous systemic treatment with either corticosteroids or
             other immunosuppressive medications within 2 weeks prior to first dose of study
             treatment.

          -  Any other concurrent antineoplastic treatment except for allowed local radiation of
             lesions for palliation.

          -  Uncontrolled or life-threatening symptomatic concomitant disease.

          -  Patients that have undergone a major surgery within 3 weeks of starting trial
             treatment or has inadequate healing or recovery from complications of surgery prior to
             starting trial treatment.

          -  Prior radiotherapy within 2 weeks of start of study treatment.

          -  Prior AHR inhibitor treatment without Sponsor permission.

          -  Potentially life-threatening second malignancy requiring systemic treatment within the
             last 3 years.

          -  Recent or current significant cardiovascular disease (e.g. stroke, heart attack, heart
             failure, or arrhythmia).

          -  Has an active infection requiring systemic therapy.

          -  A woman of child-bearing potential (WOCBP) who has a positive pregnancy test or is
             breastfeeding prior to treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of KYN-175 by characterizing type, number incidence and severity of treatment-related adverse events
Time Frame:Up to 90 days after the end of treatment (average of 7 months)
Safety Issue:
Description:Type, number, incidence and severity of treatment related adverse events as assessed by CTCAE 5.0.

Secondary Outcome Measures

Measure:Pharmacokinetics of KYN-175: half-life (t1/2)
Time Frame:Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 42 days) through end of treatment (average of 4 months)
Safety Issue:
Description:Determine KYN-175 half-life (t1/2).
Measure:Pharmacokinetics of KYN-175: Maximum Serum Concentration (Cmax)
Time Frame:Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 42 days) through end of treatment (average of 4 months)
Safety Issue:
Description:Determine KYN-175 Cmax
Measure:Pharmacokinetics of KYN-175: Area Under the Curve (AUC)
Time Frame:Days 1 and 2 of first 2 cycles (every 21 days), followed by Day 1 of every even cycle beginning with cycle 4 (every 42 days) through end of treatment (average of 4 months)
Safety Issue:
Description:Determine KYN-175 AUC
Measure:Objective response rate (ORR) of KYN-175
Time Frame:7 months
Safety Issue:
Description:Preliminary antitumor activity per RECIST 1.1 and assessment per immune Response Evaluation Criteria Solid Tumors (iRECIST) for subjects with urothelial carcinoma.
Measure:Progression-free survival (PFS) of KYN-175
Time Frame:7 months
Safety Issue:
Description:Preliminary antitumor activity per RECIST 1.1and assessment per immune Response Evaluation Criteria Solid Tumors (iRECIST) for subjects with urothelial carcinoma.
Measure:Duration of treatment (DOT) of KYN-175
Time Frame:7 months
Safety Issue:
Description:Preliminary antitumor activity per RECIST 1.1 and assessment per immune Response Evaluation Criteria Solid Tumors (iRECIST) for subjects with urothelial carcinoma.
Measure:Duration of response (DOR) of KYN-175
Time Frame:7 months
Safety Issue:
Description:Preliminary antitumor activity per RECIST 1.1 and assessment per immune Response Evaluation Criteria Solid Tumors (iRECIST) for subjects with urothelial carcinoma.
Measure:Disease control rate (DCR) of KYN-175
Time Frame:7 months
Safety Issue:
Description:Preliminary antitumor activity per RECIST 1.1 and assessment per immune Response Evaluation Criteria Solid Tumors (iRECIST) for subjects with urothelial carcinoma.
Measure:Pharmacodynamic immune effects of KYN-175 on tumor-infiltrating cytotoxic T cells
Time Frame:Prior to Cycle 1 Day 1, and anytime between the end of Cycle 1 and end of Cycle 2. Each cycle is 21 days.
Safety Issue:
Description:Characterization of tumor-infiltrating cytotoxic T cells in tumor biopsies collected before and during KYN-175 treatment

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ikena Oncology

Trial Keywords

  • IK-175
  • KYN-175
  • Immunoncology
  • Aryl Hydrocarbon Receptor Inhibitor
  • AHRi
  • Aryl Hydrocarbon Receptor Antagonist
  • Antagonist
  • Inhibitor

Last Updated

December 13, 2019