RecruitingRecruiting
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 · Eikon Therapeutics
In plain English
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Official title
A Multicenter, Multi-Part, Phase 1/2 Study of EIK1005 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors, Including Checkpoint Inhibitor Naïve Participants With Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) Tumors
About this study
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.
Eligibility criteria
Key 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.
Key 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.
Study design
Enrollment target: 160 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2026-01-20
Estimated completion: 2029-03
Last updated: 2026-04-08
Interventions
Drug: EIK1005Drug: pembrolizumab (KEYTRUDA® )
Primary outcomes
- • Dose-Limiting Toxicity (DLT) - Part 1 (21 Days)
- • Adverse Events (AEs) - Part 1 and Part 2 (From the time of first dose of study medication through 30 days following cessation of study treatment.)
Sponsor
Eikon Therapeutics · industry
With: Merck Sharp & Dohme LLC
Contacts & investigators
ContactAna C Mamede, PharmD · contact · mamedea@eikontx.com · 347-806-4584
ContactKrishna Kaza · contact · kazak@eikontx.com
InvestigatorNilou Mobashery, MD · study_director, Eikon Therapeutics, Inc.
All locations (10)
Morristown Medical CenterNot Yet Recruiting
Morristown, New Jersey, United States
Memorial Sloan Kettering Cancer Center (MSKCC)Not Yet Recruiting
New York, New York, United States
University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
GenesisCare North Shore (Oncology)Not Yet Recruiting
Saint Leonards, New South Wales, Australia
Calvary Mater Newcastle HospitalRecruiting
Waratah, New South Wales, Australia
Grampians HealthRecruiting
Ballarat, Victoria, Australia
Chris O'Brien Lifehouse (Sydney Cancer Centre)Recruiting
Camperdown, Victoria, Australia
Oncology Clinics Victoria (OCV) - Cabrini Brighton HospitalNot Yet Recruiting
Frankston, Victoria, Australia
Peninsula and Southeast Oncology (PASO) MedicalRecruiting
Frankston, Victoria, Australia
Health New ZealandRecruiting
Wellington, New Zealand