Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

Um Estudo do IDE892 como Monoterapia e em Combinação em Tumores Sólidos Avançados com Deleção de MTAP

24 de setembro de 2026 atualizado por: IDEAYA Biosciences

Um Estudo Multicêntrico a Avaliar a Segurança, Eficácia e Farmacocinética do IDE892 como Monoterapia e Terapia de Combinação em Participantes com Tumores Sólidos Avançados com Deleção de MTAP

This is a multicenter clinical study to evaluate the safety, efficacy, and Pharmacokinetics (PK) of IDE892 as monotherapy and in combination with other agents including IDE397 in participants with methylthioadenosine phosphorylase (MTAP)-deleted advanced solid tumors within indications of interest.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

The purpose of this study is to evaluate safety, efficacy, and PK of IDE892 as monotherapy and combination therapy in adult participants with MTAP-deleted tumors who have progressed after standard therapy and represent a high unmet need. In the current stage, the combination will be focused on IDE892 with IDE397, an oral inhibitor of methionine adenosyltransferase 2A (MAT2A), to fully exploit the vulnerabilities associated with methylthioadenosine (MTA) accumulation in MTAP-deleted tumors while maintaining a substantial therapeutic index. The mechanistic rationale for this study is discussed in the following sections.

Tipo de estudo

Intervencional

Inscrição (Estimado)

260

Estágio

  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

  • Estados Unidos
    • Arizona
      • Goodyear, Arizona, Estados Unidos, 85338
        • Recrutamento
        • City of Hope Cancer Center-Phoenix
        • Contato:
      • Phoenix, Arizona, Estados Unidos, 85054
        • Recrutamento
        • Mayo Clinic Arizona
        • Contato:
          • Mitesh J. Borad, M.D.
          • Número de telefone: 855-776-0015
    • California
      • Duarte, California, Estados Unidos, 91010
        • Recrutamento
        • City of Hope Cancer Center-Duarte
        • Contato:
          • Abhishek Tripathi, M.D.
          • Número de telefone: 626-218-9200
          • E-mail: atripathi@coh.org
      • Santa Rosa, California, Estados Unidos, 95403
        • Recrutamento
        • Providence Medical Foundation
        • Contato:
    • District of Columbia
      • Washington D.C., District of Columbia, Estados Unidos, 20016
    • Florida
      • Coral Springs, Florida, Estados Unidos, 33065
        • Recrutamento
        • BRCR Global-Coral Springs
        • Contato:
      • Jacksonville, Florida, Estados Unidos, 32224
        • Recrutamento
        • Mayo Clinic Florida
        • Contato:
          • Conor D. O'Donnell, M.B., B.Ch., B.A.O.
          • Número de telefone: 855-776-0015
      • Orlando, Florida, Estados Unidos, 32827
        • Recrutamento
        • Sarah Cannon Research Institute at Florida Cancer Specialists
        • Contato:
      • Tampa, Florida, Estados Unidos, 33612
    • Illinois
      • Zion, Illinois, Estados Unidos, 60099
        • Recrutamento
        • City of Hope Cancer Center-Chicago
        • Contato:
          • Evan Pisick, M.D.
          • Número de telefone: 415-353-9674
          • E-mail: episick@coh.org
    • Minnesota
      • Rochester, Minnesota, Estados Unidos, 55905
        • Recrutamento
        • Mayo Clinic Rochester
        • Contato:
          • Kaushal Parikh, M.B.B.S.
          • Número de telefone: 855-776-0015
    • Nebraska
      • Omaha, Nebraska, Estados Unidos, 68130
        • Recrutamento
        • Nebraska Cancer Specialists
        • Contato:
    • New Jersey
      • East Brunswick, New Jersey, Estados Unidos, 08816
    • New York
      • New York, New York, Estados Unidos, 10032
        • Recrutamento
        • Columbia University Irving Medical Center
        • Contato:
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos, 19107
        • Recrutamento
        • Sidney Kimmel Comprehensive Cancer Center Thomas Jefferson University
        • Contato:
        • Contato:
          • askphase1@jefferson.edu
          • Número de telefone: 215-586-0199
    • Tennessee
      • Nashville, Tennessee, Estados Unidos, 37203
        • Recrutamento
        • Sarah Cannon Research Institute
        • Contato:
        • Contato:
    • Texas
      • Fort Worth, Texas, Estados Unidos, 76104
      • Houston, Texas, Estados Unidos, 77030
        • Recrutamento
        • MD Anderson
        • Contato:
      • Houston, Texas, Estados Unidos, 77054
        • Recrutamento
        • NEXT Oncology Houston
        • Contato:
      • Irving, Texas, Estados Unidos, 75039
        • Recrutamento
        • NEXT Oncology Dallas
        • Contato:
    • Utah
      • West Valley City, Utah, Estados Unidos, 84119
        • Recrutamento
        • START Mountain Region, LLC
        • Contato:
    • Virginia
      • Fairfax, Virginia, Estados Unidos, 22031
        • Recrutamento
        • NEXT Oncology Virginia
        • Contato:
    • Washington
      • Seattle, Washington, Estados Unidos, 98104

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  • Are ≥ 18 years of age (or the minimum age of consent in accordance with local regulations) at the time of signing the ICF.
  • Have a histologically confirmed diagnosis of a locally advanced recurrent or metastatic solid tumor type of interest with MTAP deletion (for dose escalation: mesothelioma [pleural or peritoneal], gastroesophageal cancers [squamous and adenocarcinoma of esophagus, gastric adenocarcinoma, gastroesophageal junction cancers], pancreatic adenocarcinoma and biliary tract carcinomas (intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer), NSCLC [adenocarcinoma, squamous cell carcinoma, and adeno-squamous] or UC [including mixed urothelial-squamous histology]; for dose expansion: NSCLC that has progressed on at least one prior line of treatment and for which additional effective standard therapy is not available or for which the participant is not a candidate due to intolerance).
  • Are willing and able to provide blood/tumor tissue samples for biomarker testing. An archival tumor tissue specimen must be provided for central confirmation of MTAP loss.
  • Must be willing and able to provide the blood/serum/plasma samples
  • Have evidence of homozygous loss of MTAP or MTAP deletion (pre-screening available after signing pre-screening ICF)
  • Have at least 1 measurable lesion according to RECIST version 1.1
  • Have Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1
  • Have life expectancy > 3 months
  • Have adequate bone marrow and organ function
  • Able to swallow and retain orally administered study drug/IMP.
  • Are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
  • Male and female: willing to use contraception

Exclusion Criteria:

  • Known symptomatic brain metastases requiring supraphysiologic doses of systemic corticosteroids
  • Have a known primary central nervous system (CNS) malignancy
  • Have had other malignancies within 2 years prior to the first dose, with some exceptions
  • Impaired cardiac function or clinically significant cardiac diseases
  • Have presence of uncontrolled pleural, peritoneal, or pericardial effusion within 2 weeks before the first study dose, requiring recurrent drainage procedures or an indwelling drainage catheter
  • Have a history of severe infections within 4 weeks prior to the start of study treatment
  • Hypertension (e.g., > 150/100 mmHg) that cannot be controlled by medications despite optimal medical therapy
  • Other acute or chronic medical or psychiatric condition
  • Have a history of immunodeficiency, with a positive human immunodeficiency virus(HIV) test at screening
  • Known or suspected viral hepatitis with a positive test at screening
  • Had an adverse reaction to a previous antitumor treatment that has not recovered to CTCAE Grade ≤ 1
  • Have received chemotherapy within 4 weeks of the first dose of IMP; immunotherapy or biologic targeted antitumor treatments within 2 weeks before the first dose of IMP; small molecule inhibitors within 2 weeks before the first dose of IMP, or other investigational products within 4 weeks
  • Current radiation-related toxicity or radiation therapy within 2 weeks before the first dose of IMP
  • Administration of any of the following within 2 weeks before the first dose of IDE892 as a monotherapy: Strong inhibitors or inducers of cytochrome P450, Strong inhibitors of P-glycoprotein, Narrow therapeutic index and sensitive substrates of multidrug and toxin extrusion (MATE)1 and MATE2-K, Narrow therapeutic index and sensitive substrates of P-gp and breast cancer resistance protein
  • Administration of any of the following within 2 weeks before the first dose of IDE892: Strong inhibitors or inducers of CYP3A4/5, Strong inhibitors of P-gp and/or BCRP, Narrow therapeutic index and sensitive substrates of MATE1 and MATE2-K, Narrow therapeutic index and sensitive substrates of P-gp and BCRP
  • Use of proton pump inhibitors (PPIs) within 7 days prior to the first dose of IMP or planned use during the study
  • Use of drugs with known risk for QT prolongation within 2 weeks prior to the first dose of IDE892
  • Previous treatment with a Amethionine adenosyltransferase 2A (MAT2A) inhibitor and/or Protein arginine N-methyltransferase (PRMT) inhibitor
  • Major surgery within 4 weeks before study entry
  • Prior irradiation to > 25% of the bone marrow
  • Known or suspected hypersensitivity to IDE892

Disease-Specific Eligibility Criteria Eligibility Criteria for Participants with NSCLC (All Parts)

  • Must have histologically confirmed diagnosis of advanced or metastatic NSCLC that has progressed after prior treatment with platinum chemotherapy and a PD-1/PD-L1 inhibitor (unless contraindicated or participant developed intolerance) in the metastatic setting
  • Treatment with no more than 3 prior lines in the setting of advanced or metastatic disease.
  • If considered standard of care and available, participants whose cancers have proven targetable oncogene alterations must have had disease progression on (unless contraindicated or participant developed intolerance) at least 1 prior line containing appropriate targeted therapy.

Eligibility Criteria for Participants with Urothelial Cancer (Bladder and Upper Urinary Tract), Mesothelioma (Pleural or Peritoneal), Pancreatic Adenocarcinoma or Biliary Tract Carcinomas (Intrahepatic and Extrahepatic Cholangiocarcinoma, and Gallbladder Cancer) (Parts 1 and 3)

  • Must have histologically confirmed diagnosis of advanced or metastatic UC, mesothelioma, gastroesophageal cancer or pancreatic and biliary tract tumors
  • Must have progressed following at least 1 prior line of therapy
  • Treatment with no more than 3 prior lines in the setting of advanced or metastatic disease

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

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 1: IDE892 Monotherapy Dose Escalation (MTAP-deleted advanced solid tumors)

Participants with advanced or metastatic solid tumors harboring MTAP deletion (including mesothelioma, gastroesophageal cancers, pancreatic and biliary tract tumors, non-small cell lung cancer, and urothelial cancer) will receive IDE892. Dose levels will be escalated sequentially using a Bayesian Optimal Interval (BOIN) design to evaluate safety, tolerability, and to determine the maximum tolerated dose and/or recommended dose for expansion. PK and pharmacodynamics (PD) and preliminary antitumor activity will also be assessed.
Medicamento: IDE892

IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.
Experimental: Part 2: IDE892 Monotherapy Dose Expansion (MTAP-Deleted NSCLC)

Participants with advanced or metastatic NSCLC with MTAP deletion will receive IDE892. One or more dose levels at or below the maximum tolerated dose from Part 1 will be further evaluated to determine the recommended Phase 2 dose and to assess antitumor activity.
Medicamento: IDE892

IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.
Experimental: Part 3: IDE892 + IDE397 Combination Dose Escalation (MTAP-Deleted Solid Tumors)

Participants with advanced or metastatic solid tumors harboring MTAP deletion (including mesothelioma, gastroesophageal cancers, pancreatic and biliary tract tumors, non-small cell lung cancer, and urothelial cancer) will receive IDE892 in combination with IDE397. Dose levels will be escalated using a modified toxicity probability interval (mTPI) design to evaluate safety, tolerability, and to determine the maximum tolerated dose and/or recommended dose for expansion. PK, PD, and preliminary antitumor activity will also be assessed.
Medicamento: IDE892

IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.

Medicamento: IDE397

IDE397 is an oral MAT2A inhibitor that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions. In this study, IDE397 will be evaluated in combination with IDE892 (Parts 3 and 4) in participants with MTAP-deleted advanced solid tumors.
Experimental: Part 4: IDE892 + IDE397 Combination Dose Expansion (MTAP-Deleted NSCLC)

Participants with advanced or metastatic NSCLC with MTAP deletion will receive IDE892 in combination with IDE397. One or more dose levels at or below the maximum tolerated dose from Part 3 will be further evaluated to determine the recommended Phase 2 dose and to assess antitumor activity.
Medicamento: IDE892

IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.

Medicamento: IDE397

IDE397 is an oral MAT2A inhibitor that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions. In this study, IDE397 will be evaluated in combination with IDE892 (Parts 3 and 4) in participants with MTAP-deleted advanced solid tumors.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Incidence of Dose-limiting Toxicities (DLTs) of IDE892 (Parts 1 and 3)
Prazo: 21 days following the first dose of IDE892 (each cycle is 21 days)

Incidence of DLTs of IDE892 will be determined in Parts 1 and 3
21 days following the first dose of IDE892 (each cycle is 21 days)
Incidence of AEs and SAEs (Parts 1, 2, 3, and 4)
Prazo: From first dose until 28 days after last dose (each cycle is 21 days)

Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) (graded based on Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) will be determined in Parts 1, 2, 3, and 4.
From first dose until 28 days after last dose (each cycle is 21 days)
Objective response rate (ORR) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Parts 2 and 4)
Prazo: Approximately 2 years

Objective response rate (ORR: best objective response of complete response [CR] + partial response [PR]) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator
Approximately 2 years

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Overall response rate (ORR) and duration of response (DOR) per RECIST version 1.1 (Parts 1 and 3)
Prazo: Approximately 2 years

ORR and DOR per RECIST version 1.1 as assessed by the Investigator
Approximately 2 years
Disease control rate (DCR) and duration of stable disease per RECIST version 1.1 (Parts 1, 2, 3, and 4)
Prazo: Approximately 2 years

Disease control rate (disease control rate [DCR]: CR + PR + stable disease [SD]) and duration of SD per RECIST version 1.1 as assessed by the Investigator
Approximately 2 years
Maximum Observed Plasma Concentration (Cmax) (Parts 1, 2, 3, and 4)
Prazo: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Cmax is the highest observed plasma concentration of the study drug following administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Time to Maximum Observed Concentration (Tmax)
Prazo: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Time to Maximum Observed Concentration (Tmax) after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Prazo: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

AUClast reflects total drug exposure from dosing until the last measurable concentration after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Time of Last Quantifiable Concentration (Tlast)
Prazo: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Tlast is the time at which the final measurable drug concentration is observed after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf)
Prazo: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

AUCinf represents total drug exposure extrapolated to infinite time after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Terminal Elimination Half-Life (t½)
Prazo: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

t½ is the time required for the plasma concentration of the drug to decrease by half during the terminal elimination phase after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Prazo: Cycle 1 Day 15 (each cycle is 21 days)

Cmax,ss is the maximum observed plasma concentration after achieving steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Time to Maximum Concentration at Steady State (Tmax,ss)
Prazo: Cycle 1 Day 15 (each cycle is 21 days)

Tmax,ss is the time from dosing to Cmax at steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Trough Plasma Concentration at Steady State (Ctrough)
Prazo: Cycle 1 Day 15 (each cycle is 21 days)

Ctrough is the concentration obtained immediately prior to the next scheduled dose at steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUCtau)
Prazo: Cycle 1 Day 15 (each cycle is 21 days)

AUCtau represents drug exposure over one full dosing interval at steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Apparent Clearance (CL/F)
Prazo: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

CL/F is the apparent clearance of the drug after extravascular dosing after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Apparent Volume of Distribution (Vz/F)
Prazo: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Vz/F is the apparent volume of distribution following extravascular dosing after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Accumulation Ratio (Rac)
Prazo: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Rac is calculated as the ratio of AUC or Cmax at steady state compared with first dose, reflecting drug accumulation after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

IDEAYA Biosciences

Investigadores

  • Diretor de estudo: Edward Chan, MD, IDEAYA Biosciences

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

4 de março de 2026

Conclusão Primária (Estimado)

30 de abril de 2028

Conclusão do estudo (Estimado)

30 de abril de 2028

Datas de inscrição no estudo

Enviado pela primeira vez

13 de novembro de 2025

Enviado pela primeira vez que atendeu aos critérios de CQ

9 de dezembro de 2025

Primeira postagem (Real)

11 de dezembro de 2025

Atualizações de registro de estudo

Última Atualização Postada (Real)

28 de setembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

24 de setembro de 2026

Última verificação

1 de setembro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • IDE892-001

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Se inscrever