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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат EIK1005
  EIK1005 is a selective inhibitor of the Werner helicase.
• Препарат pembrolizumab (KEYTRUDA® )
  Pembrolizumab is a PD-1 inhibitor.

Первичные конечные точки

• Dose-Limiting Toxicity (DLT) - Part 1 [Срок оценки: 21 Days]
• Adverse Events (AEs) - Part 1 and Part 2 [Срок оценки: From the time of first dose of study medication through 30 days following cessation of study treatment.]

Вторичные конечные точки (9)

• Objective Response (OR) - Part 1 and Part 2 [Срок оценки: Through study completion, an average of 2 years.]
• Duration of Response (DOR) - Part 1 and Part 2 [Срок оценки: Through study completion, an average of 2 years.]
• Disease Control (DC) - Part 1 and Part 2 [Срок оценки: Through study completion, an average of 2 years.]
• Progression-free survival (PFS) - Part 2 [Срок оценки: Through study completion, an average of 2 years.]
• Pharmacokinetic (PK) parameters of EIK1005 - AUC0-24 (Part 1 and Part 2) [Срок оценки: Up to 1 year]
• Pharmacokinetic (PK) parameters of EIK1005 - AUCtau,ss (Part 1 and Part 2) [Срок оценки: Up to 1 year]
• Pharmacokinetic (PK) parameters of EIK1005 - Cmax (Part 1 and Part 2) [Срок оценки: Up to 1 year]
• Pharmacokinetic (PK) parameters of EIK1005 - tmax (Part 1 and Part 2) [Срок оценки: Up to 1 year]
• Pharmacokinetic (PK) parameters of EIK1005 - t½ (Half-life) (Part 1 and Part 2) [Срок оценки: Up to 1 year]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Австралия · 6 центров

• GenesisCare North Shore (Oncology) — Saint Leonards
• Calvary Mater Newcastle Hospital — Waratah
• Grampians Health — Ballarat
• Chris O'Brien Lifehouse (Sydney Cancer Centre) — Camperdown
• Oncology Clinics Victoria (OCV) - Cabrini Brighton Hospital — Frankston
• Peninsula and Southeast Oncology (PASO) Medical — Frankston

США · 3 центра

• Morristown Medical Center — Morristown
• Memorial Sloan Kettering Cancer Center (MSKCC) — New York
• University of Texas MD Anderson Cancer Center — Houston

Новая Зеландия · 1 центр

• Health New Zealand — Wellington

Идентификаторы

NCT: NCT07262619 · EIK1005-002 · 2026-525248-13-00 · KEYNOTE-G56 · MK-3475-G56

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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