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

NCT07262619 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: EIK1005-0022026-525248-13-00KEYNOTE-G56MK-3475-G56
• Study Type: interventional
• Target: 160
• Locations: 3 countries
• Sites: 10

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.

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

Keywords

Werner helicase; WRN; MSI-H; dMMR; DNA mismatch repair; EIK1005; Advanced Solid Tumors; Metastatic; MSI-H/dMMR Endometrial Cancer; MSI-H/dMMR Prostate Cancer; Pembrolizumab; Mismatch Repair Deficient (dMMR); Microsatellite Instability High (MSI-H)

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicity (DLT) - Part 1

  A DLT is a protocol-defined adverse event occurring during the DLT observation period.

  21 Days

• Adverse Events (AEs) - Part 1 and Part 2

  Number of participants reporting adverse events or serious adverse events.

  From the time of first dose of study medication through 30 days following cessation of study treatment.

Secondary Outcomes (9)

• Objective Response (OR) - Part 1 and Part 2

  Through study completion, an average of 2 years.

• Duration of Response (DOR) - Part 1 and Part 2

  Through study completion, an average of 2 years.

• Disease Control (DC) - Part 1 and Part 2

  Through study completion, an average of 2 years.

• Progression-free survival (PFS) - Part 2

  Through study completion, an average of 2 years.

• Pharmacokinetic (PK) parameters of EIK1005 - AUC0-24 (Part 1 and Part 2)

  Up to 1 year

Study Arms (3)

Part 1A (Dose escalation, Monotherapy)

EXPERIMENTAL

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

Drug: EIK1005

Part 1B (Dose escalation, Combination with pembrolizumab)

EXPERIMENTAL

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

Drug: EIK1005; Drug: pembrolizumab (KEYTRUDA® )

Part 2 (Dose optimization, Monotherapy)

EXPERIMENTAL

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.

Drug: EIK1005

Interventions

EIK1005 DRUG

EIK1005 is a selective inhibitor of the Werner helicase.

Part 1A (Dose escalation, Monotherapy); Part 1B (Dose escalation, Combination with pembrolizumab); Part 2 (Dose optimization, Monotherapy)

pembrolizumab (KEYTRUDA® ) DRUG

Pembrolizumab is a PD-1 inhibitor.

Part 1B (Dose escalation, Combination with pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• is ≥ 18 years of age at the time of signing the informed consent.
• has a life expectancy of at least 3 months.
• 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.
• 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.
• has measurable disease at baseline according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the PI.
• has an Eastern Cooperative Oncology Group (ECOG) score of 0 to 1.
• has an adequate organ and marrow function.

You may not qualify if:

• has not recovered (i.e., to Grade ≤ 1 or to baseline) from prior anti-cancer therapy-induced adverse events (AEs).
• has received prior treatment with Werner (WRN) inhibitor.
• 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.
• 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.
• has known additional malignancy that is progressing or has required active treatment within the past 3 years.
• 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.
• has mean resting QTcF \> 470 ms (men and women) obtained from triplicate electrocardiograms (ECGs).
• 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).
• has history of (non-infectious) pneumonitis/pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease.
• has active tuberculosis.
• has any active infections requiring systemic therapy.

Sponsors & Collaborators

• Eikon Therapeutics: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

Morristown Medical Center

Morristown, New Jersey, 07960, United States

NOT YET RECRUITING

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, 10022, United States

NOT YET RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

GenesisCare North Shore (Oncology)

Saint Leonards, New South Wales, Australia

NOT YET RECRUITING

Calvary Mater Newcastle Hospital

Waratah, New South Wales, Australia

RECRUITING

Grampians Health

Ballarat, Victoria, Australia

RECRUITING

Chris O'Brien Lifehouse (Sydney Cancer Centre)

Camperdown, Victoria, Australia

RECRUITING

Oncology Clinics Victoria (OCV) - Cabrini Brighton Hospital

Frankston, Victoria, 3199, Australia

NOT YET RECRUITING

Peninsula and Southeast Oncology (PASO) Medical

Frankston, Victoria, Australia

RECRUITING

Health New Zealand

Wellington, New Zealand

RECRUITING

MeSH Terms

Conditions

Endometrial Neoplasms; Turcot syndrome; Neoplasm Metastasis

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nilou Mobashery, MD

  Eikon Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Ana C Mamede, PharmD

CONTACT

347-806-4584; mamedea@eikontx.com

Krishna Kaza

CONTACT

kazak@eikontx.com

Study Design

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

Study Record Dates

• First Submitted: November 10, 2025
• First Posted: December 3, 2025
• Study Start: January 20, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AU (6); US (3); NZ (1)