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

NCT05228015 | Terminated Phase 1 FDA Drug

• 1 other identifier: IK930-001
• Study Type: interventional
• Target: 67
• Locations: 3 countries
• Sites: 12

Brief Summary

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.

Conditions

Solid Tumors, Adult; Solid Tumor; Malignant Pleural Mesothelioma (MPM); Epithelioid Hemangioendothelioma (EHE); NF2 Deficient Mesothelioma; Other NF2 Deficient Solid Tumors and Solid Tumors with YAP1/TAZ Fusion Genes; NF2 Deficiency; YAP1 or TAZ Gene Fusions

Keywords

IK-930; HIPPO Pathway; TEAD; YAP/TAZ; NF2 mutated tumors

Outcome Measures

Primary Outcomes (3)

• Safety and tolerability of IK-930

  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

  Approximately 1 year

• RP2D and/or MTD of IK-930

  Define the recommended phase 2 dose (RP2D) and/or MTD of IK-930

  Approximately 1 year

Secondary Outcomes (10)

• Antitumor activity per RECIST 1.1: Disease control rate (DCR) of IK-930 as a single agent

  Through study completion, average of 36 months

• Antitumor activity per RECIST 1.1: Time to response (TTR) of IK-930 as a single agent

  Through study completion, average of 36 months

• Antitumor activity per RECIST 1.1: Duration of response (DOR) of IK-930 as a single agent

  Through study completion, average of 36 months

• Antitumor activity per RECIST 1.1: Objective response rate (ORR) of IK-930 as a single agent

  Through study completion, average of 36 months

• Antitumor activity: Median progression-free survival (PFS) of IK-930 as a single agent

  Through study completion, average of 36 months

Study Arms (3)

IK-930 Single Agent Dose Escalation

EXPERIMENTAL

Drug: IK-930

IK-930 Single Agent Dose Expansion

EXPERIMENTAL

Drug: IK-930

IK-930 and Osimertinib Combination Dose Escalation

EXPERIMENTAL

Drug: IK-930; Drug: Osimertinib

Interventions

IK-930 DRUG

tablets for oral administration

IK-930 Single Agent Dose Escalation; IK-930 Single Agent Dose Expansion; IK-930 and Osimertinib Combination Dose Escalation

Osimertinib DRUG

tablets for oral administration

IK-930 and Osimertinib Combination Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ikena Oncology: lead

Study Sites (12)

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Start Midwest

Grand Rapids, Michigan, 49546, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Next Oncology

San Antonio, Texas, 78229, United States

Location

Peninsula South Eastern Haematology and Oncology Group (PASO Medical)

Frankston, Victoria, 3199, Australia

Location

University Hospitals of Leicester NHS Trust

Leicester, England, LE1 5WW, United Kingdom

Location

The Royal Marsden Hospital

London, England, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Mesothelioma, Malignant; Hemangioendothelioma, Epithelioid

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Hemangioendothelioma; Hemangioma; Neoplasms, Vascular Tissue

Study Officials

• Katherine Kim, MD

  Ikena Oncology

  STUDY DIRECTOR

• Caroline Germa, MD

  Ikena Oncology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 dose escalation: BOIN design; Part 2 dose expansion: 4 parallel cohorts, Simon 2-stage

Study Record Dates

• First Submitted: January 7, 2022
• First Posted: February 8, 2022
• Study Start: January 7, 2022
• Primary Completion: August 27, 2024
• Study Completion: September 9, 2024
• Last Updated: November 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); AU (1); US (9)