EIK1005-002: A Clinical Research Study Evaluating EIK1005, a Werner Helicase Inhibitor, as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors Including Microsatellite Instability High (MSI-H) Tumors

NCT ID: NCT07262619

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2029-03-31

Brief Summary

The goal of this clinical trial is to determine the most effective dose of EIK1005 that a person can take safely. Additionally, this study will test how well EIK1005 is tolerated alone and in combination with pembrolizumab in treating patients with advanced cancer.

Detailed Description

This Phase 1/2 study (EIK1005-002) will investigate the safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of EIK1005 as a monotherapy and in combination with pembrolizumab in participants with advanced solid tumors, including participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) Tumors.

The study will be conducted in 2 parts: Part 1 and Part 2, with Part 1 being further divided into Part 1A and Part 1B as described below:

• Part 1A (monotherapy dose escalation): participants will receive EIK1005 only.
• Part 1B (combination dose escalation): participants will receive EIK1005 in combination with pembrolizumab.
• Part 2 (dose optimization): participants will be randomized 1:1 to monotherapy with EIK1005 at one of the two selected doses from Part 1A to identify the dose of EIK1005 in monotherapy for subsequent studies.

Conditions

Advanced Solid Tumors; MSI-H or dMMR Advanced Solid Tumors; MSI-H/dMMR Gastric Cancer; MSI-H/dMMR Colorectal Cancer; MSI-H/dMMR Gastroesophageal-junction Cancer; Endometrial Cancer; Mismatch Repair Deficient or MSI-High Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1A (Dose escalation, Monotherapy)

EIK1005 will be given as monotherapy in participants without alternative treatment options.

Group Type: EXPERIMENTAL

EIK1005

Intervention Type: DRUG

EIK1005 is a selective inhibitor of the Werner helicase.

Part 1B (Dose escalation, Combination with pembrolizumab)

EIK1005 will be given in combination with pembrolizumab to participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) solid tumors.

Group Type: EXPERIMENTAL

EIK1005

Intervention Type: DRUG

EIK1005 is a selective inhibitor of the Werner helicase.

Pembrolizumab (KEYTRUDA® )

Intervention Type: DRUG

Pembrolizumab is a PD-1 inhibitor.

Part 2 (Dose optimization, Monotherapy)

Participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) advanced solid tumors will be randomized to receive EIK1005 monotherapy at one of the two identified doses selected from Part 1A.

Group Type: EXPERIMENTAL

EIK1005

Intervention Type: DRUG

EIK1005 is a selective inhibitor of the Werner helicase.

Interventions

EIK1005

EIK1005 is a selective inhibitor of the Werner helicase.

Intervention Type: DRUG

Pembrolizumab (KEYTRUDA® )

Pembrolizumab is a PD-1 inhibitor.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. is ≥ 18 years of age at the time of signing the informed consent.

2. has a life expectancy of at least 3 months.

3. has histologically or cytologically documented advanced (unresectable and/or metastatic) solid tumor. Part 1A: recommend that participants have archival tissue not more than 3 years old. Part 1B and Part 2: participant has locally confirmed Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) tumor. Participant must have archival tumor tissue (not more than 3 years old) for retrospective confirmation of MSI-H or dMMR tumor by a central laboratory.

4. In Part 1A, has received and then progressed after or is intolerant to at least 1 standard treatment regimen in the advanced setting. The participant does not have alternative therapeutic options per PI's medical judgement. Preference should be given to: (1) participants with MSI-H or dMMR cancers that have progressed after checkpoint inhibitor (CPI) therapy and (2) participants with microsatellite stable cells (MSS) cancers that have progressed following at least one regimen of platinum, alkylating or topoisomerase containing chemotherapy.

5. has measurable disease at baseline according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the PI.

6. has an Eastern Cooperative Oncology Group (ECOG) score of 0 to 1.

7. has an adequate organ and marrow function.

Exclusion Criteria

1. has not recovered (i.e., to Grade ≤ 1 or to baseline) from prior anti-cancer therapy-induced adverse events (AEs).

2. has received prior treatment with Werner (WRN) inhibitor.

3. has a history of relevant drug hypersensitivity, ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients, history of serious allergic reactions leading to hospitalization, or any other allergic reaction in general.

4. In Parts 1B and Part 2 Rescue: diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.

5. has known additional malignancy that is progressing or has required active treatment within the past 3 years.

6. has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during the study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study treatment.

7. has mean resting QTcF > 470 ms (men and women) obtained from triplicate electrocardiograms (ECGs).

8. has active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Participants may enroll with the following conditions: Type 1 diabetes, hypothyroidism requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia not requiring systemic treatment).

9. has history of (non-infectious) pneumonitis/pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease.

10. has active tuberculosis.

11. has any active infections requiring systemic therapy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eikon Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nilou Mobashery, MD

Role: STUDY_DIRECTOR

Eikon Therapeutics, Inc.

Locations

Morristown Medical Center

Morristown, New Jersey, United States

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Calvary Mater Newcastle Hospital

Waratah, New South Wales, Australia

Illawarra Cancer Care Centre (ICCC)

Wollongong, New South Wales, Australia

Chris O'Brien Lifehouse (Sydney Cancer Centre)

Camperdown, Victoria, Australia

Peninsula and Southeast Oncology (PASO) Medical

Frankston, Victoria, Australia

Olivia Newton John Cancer Research Institute

Heidelberg, Victoria, Australia

Countries

United States; Australia

Central Contacts

Aishwarya Movva

Role: CONTACT

movvaa@eikontx.com

408-520-0596

Other Identifiers

EIK1005-002

Identifier Type: -

Identifier Source: org_study_id