Oral TEAD Inhibitor Targeting the Hippo Pathway in Subjects With Advanced Solid Tumors

April 11, 2024 updated by: Ikena Oncology

A Phase 1, First-in-Human Study of IK-930, an Oral TEAD Inhibitor Targeting the Hippo Pathway in Subjects With Advanced Solid Tumors

This is a Phase 1, first-in-human (FIH) clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of IK-930, an oral TEAD inhibitor, administered orally (PO) as monotherapy in subjects with advanced solid tumors with or without gene alterations in the Hippo pathway for whom there are no further treatment options known to confer clinical benefit. The study consists of two phases, an initial Dose Escalation phase followed by a Dose Expansion phase.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

198

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
    • England
      • Leicester, England, United Kingdom, LE1 5WW
        • Recruiting
        • University Hospitals Of Leicester Nhs Trust
        • Contact:
        • Principal Investigator:
          • Dean Fennell, MBBS, PhD, FRCP
      • London, England, United Kingdom, SW3 6JJ
        • Recruiting
        • The Royal Marsden Hospital
        • Contact:
        • Principal Investigator:
          • Robin Jones, BSc, MB BS, MRCP, MD
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Not yet recruiting
        • University of California Los Angeles
        • Contact:
        • Principal Investigator:
          • Robert Cameron, MD
    • Illinois
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Gregory Cote, MD, PhD
        • Contact:
          • Gregory Cote, MD, PhD
          • Phone Number: 617-724-4000
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • Start Midwest
        • Principal Investigator:
          • Nehal Lakhani, MD, PhD
        • Contact:
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Principal Investigator:
          • Mrinal Gounder, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania Abramson Cancer Center
        • Principal Investigator:
          • Melina Marmarelis, MD
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital
        • Contact:
        • Principal Investigator:
          • Babar Bashir, MD
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute
        • Contact:
          • askSARAH
          • Phone Number: 844-482-4812
        • Principal Investigator:
          • Meredith McKean, MD, MPH
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Principal Investigator:
          • Vinod Ravi, MD
        • Contact:
        • Contact:
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • NEXT Oncology
        • Contact:
        • Principal Investigator:
          • Anthony Tolcher, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Signed informed consent must be obtained prior to participation in the study.
  2. Male or female subjects ≥ 18 years of age.
  3. If feasible, subjects must be willing to consent to the submission of formalin-fixed paraffin-embedded tissue blocks or slides of tumor tissue, preferably from pre-treatment, baseline fresh tumor biopsy at Screening. Alternatively, archival tumor FFPE blocks or, unstained slides of tumor tissue from available archival sources are acceptable.
  4. In the dose escalation cohort: Subjects with histologically proven advanced, unresectable, locally recurrent, or metastatic malignancy that has progressed on or following standard-of-care therapies and for whom there is no available therapy known to confer clinical benefit, regardless of the presence or absence of NF2 deficiency or other genetic alterations of the Hippo pathway. Subjects with histological confirmation of MPM; subjects with NF2-deficient MPM determined by local test results for testing can also be enrolled as well as subjects with any other solid tumors with documented NF2 deficiency determined by local test results for testing, including, but not limited to, meningioma, cholangiocarcinoma, thymoma, mucoepidermoid NSCLC, HCC, and others. Subjects diagnosed with EHE with documented TAZ-CAMTA1 or YAP1-TFE3 gene fusions, as determined by local tests and subjects with solid tumors who have YAP1/TAZ gene fusions as determined by local test results can also be enrolled in the dose escalation part of the study.

  5. In the Dose expansion: Four groups of subjects will be enrolled:

    1. Cohort 1: Subjects with histological confirmed MPM and that have documented NF2 deficiency,
    2. Cohort 2: Subjects with other documented NF2-deficient solid tumors agnostic to tumor type including, but not limited to, meningioma, cholangiocarcinoma, thymoma, NSCLC, HCC, and others.
    3. Cohort 3: Subjects with histopathological diagnosis of epithelioid hemangioendothelioma (EHE) and documented TAZ-CAMTA1 or YAP1-TFE3 gene fusions, as determined by local test results. Subjects who have objective disease progression to prior therapy or have active disease and cancer-related pain requiring narcotics for management are eligible.
    4. Cohort 4: Subjects with any solid tumor with documented YAP1/TAZ gene fusions as determined by local test results.
  6. In the Osimertinib Combination Cohort subjects must have a histologically proven, incurable, locally advanced or metastatic NSCLC expressing osimertinib-sensitive EGFR mutations; have evidence of radiological disease progression on prior receipt of Osimertinib and have progressed on additional anticancer therapy such as chemotherapy.
  7. Subjects can have measurable or evaluable disease by RECIST 1.1 criteria as assessed by the Investigator/local radiologist.

Exclusion Criteria:

  1. Subjects with untreated or symptomatic primary central nervous system (CNS) tumors or with intracranial metastases (excluding primary CNS tumors that may be eligible for enrollment as part of Cohort 2 e.g., NF-2 deficient meningioma)

    a. Subjects with leptomeningeal metastases are excluded

  2. Uncontrolled or life-threatening symptomatic concomitant disease
  3. Clinically significant cardiovascular disease as defined in the protocol
  4. Women who are pregnant or breastfeeding
  5. Subjects who are unable to swallow or retain oral medication
  6. Prior treatment/exposure to YAP/TAZ/TEAD inhibitors
  7. Other inclusion/exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IK-930 Single Agent Dose Escalation
Drug: IK-930
tablets for oral administration
Experimental: IK-930 Single Agent Dose Expansion
Drug: IK-930
tablets for oral administration
Experimental: IK-930 and Osimertinib Combination Dose Escalation
Drug: IK-930
tablets for oral administration
Drug: Osimertinib
tablets for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of IK-930
Time Frame: Through study completion, an average of 36 months
The frequency and severity, incidence of treatment-emergent and treatment-related adverse events using NCI-CTCAE v5.0
Through study completion, an average of 36 months
Occurrence of Dose Limiting Toxicity during first treatment cycle
Time Frame: Approximately 1 year
Approximately 1 year
RP2D and/or MTD of IK-930
Time Frame: Approximately 1 year
Define the recommended phase 2 dose (RP2D) and/or MTD of IK-930
Approximately 1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Antitumor activity per RECIST 1.1: Disease control rate (DCR) of IK-930 as a single agent
Time Frame: Through study completion, average of 36 months
Through study completion, average of 36 months
Antitumor activity per RECIST 1.1: Time to response (TTR) of IK-930 as a single agent
Time Frame: Through study completion, average of 36 months
Through study completion, average of 36 months
Antitumor activity per RECIST 1.1: Duration of response (DOR) of IK-930 as a single agent
Time Frame: Through study completion, average of 36 months
Through study completion, average of 36 months
Antitumor activity per RECIST 1.1: Objective response rate (ORR) of IK-930 as a single agent
Time Frame: Through study completion, average of 36 months
Through study completion, average of 36 months
Antitumor activity: Median progression-free survival (PFS) of IK-930 as a single agent
Time Frame: Through study completion, average of 36 months
Through study completion, average of 36 months
Antitumor activity: Median overall survival (OS) of IK-930 as a single agent
Time Frame: Through study completion, average of 36 months
Through study completion, average of 36 months
Pharmacokinetics of IK-930: half-life (t1/2)
Time Frame: Approximately 1 year
Approximately 1 year
Pharmacokinetics of IK-930: Area Under the Curve (AUC)
Time Frame: Approximately 1 year
Approximately 1 year
Pharmacokinetics of IK-930: Maximum Plasma Concentration (Cmax)
Time Frame: Approximately 1 year
Approximately 1 year
Pharmacokinetics of IK-930: Minimum Plasma Concentration (Cmin)
Time Frame: Approximately 1 year
Approximately 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ikena Oncology

Investigators

  • Study Director: Katherine Kim, MD, Ikena Oncology
  • Study Chair: Caroline Germa, MD, Ikena Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 7, 2022

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

January 7, 2022

First Submitted That Met QC Criteria

January 27, 2022

First Posted (Actual)

February 8, 2022

Study Record Updates

Last Update Posted (Actual)

April 12, 2024

Last Update Submitted That Met QC Criteria

April 11, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IK930-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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