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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05228015
• Other study ID #: IK930-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 7, 2022
• Est. completion date: June 2025

Study information

• Verified date: June 2024
• Source: Ikena Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 198
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemangioendothelioma
• Malignant Pleural Mesothelioma (MPM)
• Mesothelioma
• Mesothelioma, Malignant
• Neoplasms
• Solid Tumor
• Solid Tumors, Adult

Intervention

Drug:
• IK-930
tablets for oral administration
• Osimertinib
tablets for oral administration

Locations

Country	Name	City	State
United Kingdom	University Hospitals of Leicester NHS Trust	Leicester	England
United Kingdom	The Royal Marsden Hospital	London	England
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of Chicago	Chicago	Illinois
United States	Start Midwest	Grand Rapids	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Next Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Ikena Oncology

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Occurrence of Dose Limiting Toxicity during first treatment cycle		Approximately 1 year
Primary	RP2D and/or MTD of IK-930	Define the recommended phase 2 dose (RP2D) and/or MTD of IK-930	Approximately 1 year
Secondary	Antitumor activity per RECIST 1.1: Disease control rate (DCR) of IK-930 as a single agent		Through study completion, average of 36 months
Secondary	Antitumor activity per RECIST 1.1: Time to response (TTR) of IK-930 as a single agent		Through study completion, average of 36 months
Secondary	Antitumor activity per RECIST 1.1: Duration of response (DOR) of IK-930 as a single agent		Through study completion, average of 36 months
Secondary	Antitumor activity per RECIST 1.1: Objective response rate (ORR) of IK-930 as a single agent		Through study completion, average of 36 months
Secondary	Antitumor activity: Median progression-free survival (PFS) of IK-930 as a single agent		Through study completion, average of 36 months
Secondary	Antitumor activity: Median overall survival (OS) of IK-930 as a single agent		Through study completion, average of 36 months
Secondary	Pharmacokinetics of IK-930: half-life (t1/2)		Approximately 1 year
Secondary	Pharmacokinetics of IK-930: Area Under the Curve (AUC)		Approximately 1 year
Secondary	Pharmacokinetics of IK-930: Maximum Plasma Concentration (Cmax)		Approximately 1 year
Secondary	Pharmacokinetics of IK-930: Minimum Plasma Concentration (Cmin)		Approximately 1 year