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

Study Identifier:
IK930-001
CT.gov Identifier:
NCT05228015
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
2022-502622-40-00
Study Contact Information:
(210) 593-5651 or [email protected]
Terminated/Withdrawn

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Study Summary

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

To evaluate the safety and tolerability of IK-930 as monotherapy, and to determine the recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) using the Bayesian Optimal Interval Design (BOIN)

A dose expansion phase will follow with four genetically defined cohorts of solid tumors, including: NF2-deficient MPM (Cohort 1), other NF2-deficient solid tumors agnostic to tumor type (Cohort 2), EHE with TAZ-CAMTA1 or YAP1-TFE3 gene fusions (Cohort3), and solid tumors with YAP1/TAZ gene fusions agnostic to tumor type (Cohort 4).

Medical Condition
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.
  • Breast Cancers
  • Non-Small Cell Lung Cancer
  • Ovarian
  • Liver
  • Solid Tumor
  • Soft Tissue Sarcoma
  • Mesothelioma
  • Endometrial
  • Cervical cancer
  • Bile Duct
  • Thymus
  • CNS, Meningioma
    • 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.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: IK-930 Single Agent Dose Escalation Drug: IK-930
    • Read More
  • Drug: Experimental: IK-930 Single Agent Dose Expansion Drug: IK-930
  • Drug: Experimental: IK-930 and Osimertinib Combination Dose Escalation Drug: IK-930
  • Drug: Drug: Osimertinib
  • Drug: Patients will receive escalating doses of IK-930 starting at 25mg daily. IK-930 will be administered initially in a 28-day cycle and will progress to a 21-day cycle when evaluated as safe and well-tolerated.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Terminated/Withdrawn

    Requirements information
    Inclusion criteria
    • Signed informed consent must be obtained prior to participation in the study.
    • Male or female subjects ≥ 18 years of age.
    • 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.
    • 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.
    • In the Dose expansion: Four groups of subjects will be enrolled:
    • Cohort 1: Subjects with histological confirmed MPM and that have documented NF2 deficiency,
    • 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.
    • 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.
    • Cohort 4: Subjects with any solid tumor with documented YAP1/TAZ gene fusions as determined by local test results.
    • 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.
    • Subjects can have measurable or evaluable disease by RECIST 1.1 criteria as assessed by the Investigator/local radiologist.
    Exclusion criteria
    • 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
    • Uncontrolled or life-threatening symptomatic concomitant disease
    • Clinically significant cardiovascular disease as defined in the protocol
    • Women who are pregnant or breastfeeding
    • Subjects who are unable to swallow or retain oral medication
    • Prior treatment/exposure to YAP/TAZ/TEAD inhibitors
    • Other inclusion/exclusion criteria may apply

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Nehal Lakhani
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Breast Cancers
    Non-Small Cell Lung Cancer
    Ovarian
    Liver
    Solid Tumor
    Soft Tissue Sarcoma
    Mesothelioma
    Endometrial
    Cervical cancer
    Bile Duct
    Thymus
    CNS, Meningioma