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

Sponsor

Ikena Oncology (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05228015

Collaborator

(none)

158

Enrollment

Locations

Arms

32.8

Anticipated Duration (Months)

26.3

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors, Adult Solid Tumor 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	Drug: IK-930	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

158 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

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

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 7, 2022

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: IK-930 Single Agent Dose Escalation	Drug: IK-930 tablets for oral administration
Experimental: Experimental: IK-930 Single Agent Dose Expansion	Drug: IK-930 tablets for oral administration

Arm

Intervention/Treatment

Experimental: Experimental: IK-930 Single Agent Dose Escalation

Drug: IK-930

tablets for oral administration

Experimental: Experimental: IK-930 Single Agent Dose Expansion

Drug: IK-930

tablets for oral administration

Outcome Measures

Primary Outcome Measures

Safety and tolerability of IK-930 [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
Occurrence of Dose Limiting Toxicity during first treatment cycle [Approximately 1 year]
RP2D and/or MTD of IK-930 [Approximately 1 year]
Define the recommended phase 2 dose (RP2D) and/or MTD of IK-930

Secondary Outcome Measures

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]
Antitumor activity: Median overall survival (OS) of IK-930 as a single agent [Through study completion, average of 36 months]
Pharmacokinetics of IK-930: half-life (t1/2) [Approximately 1 year]
Pharmacokinetics of IK-930: Area Under the Curve (AUC) [Approximately 1 year]
Pharmacokinetics of IK-930: Maximum Plasma Concentration (Cmax) [Approximately 1 year]
Pharmacokinetics of IK-930: Minimum Plasma Concentration (Cmin) [Approximately 1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 of tumor tissue, preferably from pre-treatment fresh tumor biopsy. Alternatively, archival tumor FFPE blocks or, preferably, 10 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 RNA-seq, FISH or IHC and subjects with solid tumors who have YAP1/TAZ gene fusions as determined by RNA-seq, FISH or IHC, as documented 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 for RNA-seq, FISH or IHC. 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 for RNA-seq, FISH or IHC.
Subjects can have measurable or evaluable disease by RECIST 1.1 criteria as assessed by the Investigator/local radiologist.
Comply with the study protocol and with the planned biopsy procedures.

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)

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
Other inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ikena Investigational site	Boston	Massachusetts	United States	02215
2	Ikena Investigational site	Grand Rapids	Michigan	United States	49546
3	Ikena Investigational site	Philadelphia	Pennsylvania	United States	19107
4	Ikena Investigational Site	Nashville	Tennessee	United States	37203
5	Ikena Investigational site	Houston	Texas	United States	77030
6	Ikena Investigational site	San Antonio	Texas	United States	78229