EIK1005 (Werner helicase inhibitor) alone or with pembrolizumab for advanced MSI-H/dMMR and other solid tumors

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

This trial tests whether EIK1005, given alone or together with pembrolizumab, can be safely given and help people with advanced solid tumors, especially MSI‑H/dMMR cancers.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Eikon Therapeutics (industry)
• Drugs / interventions: chemotherapy, prednisone, pembrolizumab
• Locations: 10 sites (Morristown, New Jersey and 9 other locations)
• Trial ID: NCT07262619 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 trial tests escalating doses of EIK1005 as monotherapy (Part 1A) and combined with pembrolizumab (Part 1B) to identify safe and tolerable dose levels. Investigators will collect safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity data across dose cohorts. In Part 2, participants with MSI‑H/dMMR tumors will be randomized 1:1 to one of two selected monotherapy doses from Part 1A to choose an optimal dose for later studies. Enrollment focuses on adults with unresectable or metastatic solid tumors, with central confirmation of MSI‑H/dMMR status required for combination and Part 2 cohorts.

Who should consider this trial

Good fit: Adults (≥18) with unresectable or metastatic solid tumors who have progressed on or are intolerant to standard treatments and, for the combination and Part 2, have confirmed MSI‑H/dMMR tumor tissue, are eligible.

Not a fit: Patients with early-stage disease, those unable to provide recent archival tumor tissue for MSI‑H/dMMR confirmation, or those who are medically unfit for investigational therapy or immunotherapy are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this could offer a new targeted therapy option alone or combined with pembrolizumab for patients with MSI‑H/dMMR or other advanced solid tumors.

How similar studies have performed: Checkpoint inhibitors like pembrolizumab have established benefit in MSI‑H cancers, but WRN (Werner helicase) inhibition is a novel approach with limited prior clinical data, so the combination remains largely untested in humans.

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.

Where this trial is running

Morristown, New Jersey and 9 other locations

• Morristown Medical Center — Morristown, New Jersey, United States (NOT_YET_RECRUITING)
• Memorial Sloan Kettering Cancer Center (MSKCC) — New York, New York, United States (NOT_YET_RECRUITING)
• University of Texas MD Anderson Cancer Center — Houston, Texas, 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, Australia (NOT_YET_RECRUITING)
• Peninsula and Southeast Oncology (PASO) Medical — Frankston, Victoria, Australia (RECRUITING)
• Health New Zealand — Wellington, New Zealand (RECRUITING)

Study contacts

• Study coordinator: Ana C Mamede, PharmD

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, Werner helicase