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

November 14, 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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
67

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Australia
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Peninsula South Eastern Haematology and Oncology Group (PASO Medical)
  • United Kingdom
    • England
      • Leicester, England, United Kingdom, LE1 5WW
        • University Hospitals of Leicester NHS Trust
      • London, England, United Kingdom, SW3 6JJ
        • The Royal Marsden Hospital
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Massachusetts General Hospital
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • START Midwest
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Abramson Cancer Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • Next Oncology

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ikena Oncology

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 7, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 27, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 9, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 7, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 27, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 8, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 18, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

product manufactured in and exported from the U.S.

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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