EIK1005-002: Um Estudo de Investigação Clínica a Avaliar o EIK1005, um Inibidor da Helicase de Werner, em Monoterapia e em Combinação com Pembrolizumab em Participantes com Tumores Sólidos Avançados Incluindo Tumores com Alta Instabilidade de Microssatélites (MSI-H)
Um Estudo Multicêntrico, Multi-Parte, de Fase 1/2 do EIK1005 como Monoterapia e em Combinação com Pembrolizumab em Participantes com Tumores Sólidos Avançados, Incluindo Participantes Ingénuos a Inibidores de Checkpoint com Tumores de Alta Instabilidade de Microssatélites (MSI-H) ou com Deficiência de Reparação de Erros de Pareamento (dMMR)
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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Ana C Mamede, PharmD
- Número de telefone: 347-806-4584
- E-mail: mamedea@eikontx.com
Estude backup de contato
- Nome: Krishna Kaza
- E-mail: kazak@eikontx.com
Locais de estudo
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Berlin, Alemanha, 13125
- Recrutamento
- Helios Klinikum Berlin-Buch
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Hamburg, Alemanha, 22297
- Recrutamento
- Norddeutsches Studienzentrum fur Innovative Onkologie (NIO) Hamatologisch Onkologische Praxis Eppendorf (HOPE)
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Bavaria
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Deggendorf, Bavaria, Alemanha, 94469
- Recrutamento
- DONAUISAR Klinikum
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New South Wales
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Saint Leonards, New South Wales, Austrália
- Ainda não está recrutando
- GenesisCare North Shore (Oncology)
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Waratah, New South Wales, Austrália
- Recrutamento
- Calvary Mater Newcastle Hospital
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Victoria
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Ballarat, Victoria, Austrália
- Recrutamento
- Grampians Health
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Camperdown, Victoria, Austrália
- Recrutamento
- Chris O'Brien Lifehouse (Sydney Cancer Centre)
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Frankston, Victoria, Austrália
- Recrutamento
- Peninsula and Southeast Oncology (PASO) Medical
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Frankston, Victoria, Austrália, 3199
- Recrutamento
- Oncology Clinics Victoria (OCV) - Cabrini Brighton Hospital
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Brussels, Bélgica, 1020
- Recrutamento
- Centre Hospitalier Universitaire Brugmann - Victor Horta
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Singapore, Cingapura, 119074
- Recrutamento
- National University Hospital (NUH)
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Central Region
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Singapore, Central Region, Cingapura, 168583
- Recrutamento
- National Cancer Centre Singapore (NCCS)
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Seoul, Coréia do Sul, 02841
- Recrutamento
- Korea University Anam Hospital
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Suwon, Coréia do Sul, 16499
- Recrutamento
- Ajou University School of Medicine & Graduate School of Medicine
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Busan
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Busan, Busan, Coréia do Sul, 48108
- Recrutamento
- Inje University-Haeundae Paik Hospital
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Barcelona, Espanha, 08023
- Recrutamento
- START - Barcelona
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Logroño, Espanha, 26006
- Recrutamento
- START Rioja - Hospital de San Pedro
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Madrid, Espanha, 28233
- Recrutamento
- NEXT Madrid HUQSM
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Zaragoza, Espanha, 50009
- Recrutamento
- Hospital Universitario Miguel Servet
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Balearic Islands
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Palma, Balearic Islands, Espanha, 07120
- Recrutamento
- Hospital Universitari Son Espases
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Barcelona
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Barcelona, Barcelona, Espanha, 8036
- Recrutamento
- Hospital Clinic Barcelona
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California
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Los Angeles, California, Estados Unidos, 90027
- Recrutamento
- California Research Institute (CRI)
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Florida
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Doral, Florida, Estados Unidos, 33172
- Recrutamento
- Omnicure Clinical Research
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Hialeah, Florida, Estados Unidos, 33013
- Recrutamento
- Bioresearch Partner
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Plantation, Florida, Estados Unidos, 33322
- Recrutamento
- Florida Clinical Trials Group
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Tamarac, Florida, Estados Unidos, 33321
- Recrutamento
- Florida Clinical Trials Group - Tamarac
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New Jersey
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Morristown, New Jersey, Estados Unidos, 07960
- Recrutamento
- Morristown Medical Center
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New York
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Lake Success, New York, Estados Unidos, 11042
- Recrutamento
- START New York-Long Island
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New York, New York, Estados Unidos, 10022
- Recrutamento
- Memorial Sloan Kettering Cancer Center (MSKCC)
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Texas
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Fort Worth, Texas, Estados Unidos, 76104
- Recrutamento
- START Dallas Fort Worth
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Houston, Texas, Estados Unidos, 77030
- Recrutamento
- University of Texas MD Anderson Cancer Center
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Kuopio, Finlândia, 70210
- Recrutamento
- Kuopio University Hospital
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Rhone
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Pierre-Bénite, Rhone, França, 69310
- Recrutamento
- Hospices Civils De Lyon (hcl) -Centre Hospitalier Lyon-Sud
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Rome, Itália, 00128
- Recrutamento
- Campus Bio-Medico di Rome University
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Oslo, Noruega, 0379
- Recrutamento
- Oslo University
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Wellington, Nova Zelândia
- Recrutamento
- Health New Zealand
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Manawatu
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Roslyn, Manawatu, Nova Zelândia, 4414
- Recrutamento
- Palmerstone North Hospital
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Krakow, Polônia, 31-864
- Recrutamento
- GCPMED Sp. z o.o., Centrum Medyczne iMed24
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Lodz, Polônia, 90-338
- Recrutamento
- Centrum Terapii Wspolczesnej J.M. Jasnorzewska Spolka Komandytowo-Akcyjna
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West Pomeranian Voivodeship
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Szczecin, West Pomeranian Voivodeship, Polônia, 70-419
- Recrutamento
- One Day Med
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Lisbon, Portugal, 1649-028
- Recrutamento
- Hospital de Santa Maria
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Loures, Portugal, 2674-514
- Recrutamento
- Unidade Local de Saúde (ULS) Loures Odivelas
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Porto, Portugal, 4200
- Recrutamento
- Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E. (IPO Porto)
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Lisbon District
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Lisbon, Lisbon District, Portugal, 1500-650
- Recrutamento
- Hospital da Luz Lisboa
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Linz, Áustria, 4020
- Recrutamento
- Ordensklinikum Linz Elisabethinen
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Key Inclusion Criteria:
- 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.
Key Exclusion Criteria:
- 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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Part 1A (Dose escalation, Monotherapy)
EIK1005 will be given as monotherapy in participants without alternative treatment options. |
EIK1005 is a selective inhibitor of the Werner helicase. |
|
Experimental: 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. |
EIK1005 is a selective inhibitor of the Werner helicase. Pembrolizumab is a PD-1 inhibitor. |
|
Experimental: 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. |
EIK1005 is a selective inhibitor of the Werner helicase. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Dose-Limiting Toxicity (DLT) - Part 1
Prazo: 21 Days
|
A DLT is a protocol-defined adverse event occurring during the DLT observation period. |
21 Days
|
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Adverse Events (AEs) - Part 1 and Part 2
Prazo: From the time of first dose of study medication through 30 days following cessation of study treatment.
|
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.
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Objective Response (OR) - Part 1 and Part 2
Prazo: Through study completion, an average of 2 years.
|
OR defined as participants who have a complete response [CR] or partial response [PR] by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1 as assessed by the Investigator. |
Through study completion, an average of 2 years.
|
|
Duration of Response (DOR) - Part 1 and Part 2
Prazo: Through study completion, an average of 2 years.
|
DOR (defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first, in participants demonstrating CR or PR) by RECIST 1.1 as assessed by the Investigator. |
Through study completion, an average of 2 years.
|
|
Disease Control (DC) - Part 1 and Part 2
Prazo: Through study completion, an average of 2 years.
|
DC defined as participants with a best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD) by RECIST 1.1 as assessed by the Investigator. |
Through study completion, an average of 2 years.
|
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Progression-free survival (PFS) - Part 2
Prazo: Through study completion, an average of 2 years.
|
PFS defined as the time from randomization to the first documented disease progression by RECIST 1.1 as assessed by the Investigator or death due to any cause, whichever occurs first. |
Through study completion, an average of 2 years.
|
|
Pharmacokinetic (PK) parameters of EIK1005 - AUC0-24 (Part 1 and Part 2)
Prazo: Up to 1 year
|
AUC0-24 (Area Under the plasma Concentration versus time curve from 0 to 24 hours): Measures total drug exposure over the first 24 hours after dosing of EIK1005 as monotherapy and in combination with pembrolizumab. |
Up to 1 year
|
|
Pharmacokinetic (PK) parameters of EIK1005 - AUCtau,ss (Part 1 and Part 2)
Prazo: Up to 1 year
|
AUCtau,ss [Area Under the plasma Concentration versus time curve over one dosing interval (tau) at steady state]: Reflects average drug exposure during each dosing interval once the steady state has been reached for EIK1005 as monotherapy and in combination with pembrolizumab. |
Up to 1 year
|
|
Pharmacokinetic (PK) parameters of EIK1005 - Cmax (Part 1 and Part 2)
Prazo: Up to 1 year
|
Cmax (Maximum Plasma Concentration) after dose administration of EIK1005 as monotherapy and in combination with pembrolizumab. |
Up to 1 year
|
|
Pharmacokinetic (PK) parameters of EIK1005 - tmax (Part 1 and Part 2)
Prazo: Up to 1 year
|
tmax (the time required for the plasma concentration of the drug to reach maximum concentration after dose administration) of EIK1005 as monotherapy and in combination with pembrolizumab. |
Up to 1 year
|
|
Pharmacokinetic (PK) parameters of EIK1005 - t½ (Half-life) (Part 1 and Part 2)
Prazo: Up to 1 year
|
Half-life (the time required for the plasma concentration of the drug to decrease by 50% after the dose administration) of EIK1005 as monotherapy and in combination with pembrolizumab. |
Up to 1 year
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Diretor de estudo: Nilou Mobashery, MD, Eikon Therapeutics, Inc.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças urogenitais
- Doenças Genitais
- Processos Patológicos
- Neoplasias urogenitais
- Neoplasias por local
- Neoplasias
- Doenças Urogenitais Femininas
- Doenças urogenitais femininas e complicações na gravidez
- Doenças uterinas
- Doenças Genitais Femininas
- Processos Neoplásicos
- Neoplasias Genitais Femininas
- Neoplasias uterinas
- Condições Patológicas, Sinais e Sintomas
- Neoplasia Metástase
- Neoplasias endometriais
- Síndrome do turco
- Pembrolizumab
Outros números de identificação do estudo
- EIK1005-002
- 2026-525248-13-00 (Ctis)
- KEYNOTE-G56 (Outro identificador: Merck Sharp & Dohme LLC)
- MK-3475-G56 (Outro identificador: Merck Sharp & Dohme LLC)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Informações sobre medicamentos e dispositivos, documentos de estudo
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