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

A Study to Investigate the Safety and Tolerability of Oral INR731 Single Agent or in Combination With Androgen Receptor Pathway Inhibitor (ARPI) in Patients With Metastatic Prostate Cancer

27 de maio de 2026 atualizado por: Novartis Pharmaceuticals

An Open-label, Multi-center, First in Human Phase I Global Dose Escalation and Expansion Study of INR731 Single Agent or in Combination With an Androgen Receptor Pathway Inhibitor in Patients With Metastatic Prostate Cancer

The purpose of this study is to assess the safety, tolerability, pharmacokinetics/pharmacodynamics, preliminary anti-tumor activity, and recommended dose of INR731 as a single agent and in combination with standard-of-care androgen receptor pathway inhibitors (ARPIs) in adult patients with metastatic prostate cancer.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

This is a first-in-human, open-label, phase I, multi-center study which consists of three treatment arms: INR731 single agent (Arm A), and INR731 in combination with enzalutamide (Arm B) or abiraterone (Arm C).

The single agent arm has a dose escalation part followed by a dose expansion part. Once the single agent recommended dose(s) is determined during dose escalation, the study may proceed to dose expansion to further explore safety, tolerability and preliminary anti-tumor activity. The single agent dose expansion part will include a post-standard of care (SOC) metastatic castration resistant prostate cancer (mCRPC) group and patients with time to castration resistance (TTCR) <12 months.

The combination arms have a dose escalation of INR731 in combination with enzalutamide or abiraterone followed by a dose expansion of INR731 in combination with enzalutamide only. The combination dose escalation will be conducted in patients with mCRPC who have progressed following standard of care (post-SOC). During combination escalation, once the safety and tolerability of INR731 with the combination agent(s) is assessed, the study may proceed to dose expansion. The combination dose expansion part will include first-line (1L) mCRPC patients with no prior treatment in the mCRPC setting.

Tipo de estudo

Intervencional

Inscrição (Estimado)

208

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

Estude backup de contato

  • Nome: Novartis Pharmaceuticals
  • Número de telefone: +41613241111

Locais de estudo

  • Austrália
    • Victoria
      • Melbourne, Victoria, Austrália, 3000
        • Recrutamento
        • Novartis Investigative Site
  • Estados Unidos
    • Texas
      • Dallas, Texas, Estados Unidos, 75251
        • Recrutamento
        • Mary Crowley Cancer Research
        • Investigador principal:
          • Reva Schneider
        • Contato:

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

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

Inclusion Criteria:

  • An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤2.
  • Participants must have histological and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are eligible as long as the non-adenocarcinoma feature is the minority component.
  • At least 1 metastatic lesion (according to local radiology assessment by the investigator) present on baseline CT, MRI, or bone scan imaging obtained ≤28 days prior to Cycle 1 Day 1 (C1D1).
  • Patients must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L).
  • Ongoing androgen deprivation therapy (ADT) either via orchiectomy and/or ongoing gonadotropin-releasing hormone (GnRH) analog or inhibitor is allowed.
  • Participants must be mCRPC patients who have either progressed on or are not candidates for other SOC. Prior taxane, poly(ADP) ribose polymerase (PARP) inhibitor, and lutetium Lu 177 vipivotide tetraxetan (Pluvicto) are allowed. Combination expansion patients, however, must be 1L mCRPC with no prior treatment in the mCRPC setting. Treatment within the mHSPC setting does not affect eligibility.

Exclusion Criteria:

  • Age < 18 years old.
  • Histological and/or cytological confirmation of non-adenocarcinoma of the prostate.
  • Patients with biochemical recurrence only or those without evidence of metastatic disease by radiographical imaging (CT/MRI or bone scan) are not eligible.
  • Patients previously treated with a cereblon-based degrader.
  • Patients who are HIV+ or immune compromised.
  • Use of agents known to prolong QT interval unless they can be permanently discontinued for the duration of the study
  • Treatment with an investigational agent within 7 days (or 5 half-lives, whichever is longer) of the anticipated Cycle 1 Day 1 (C1D1).

Other protocol-defined inclusion/exclusion criteria may apply.

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: INR731 single agent (Arm A)
The dose escalation part with single agent INR731 may be followed by a dose expansion part.
Medicamento: INR731
Oral administration
Medicamento: Androgen deprivation therapy (ADT)
Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care.
Experimental: INR731 in combination with enzalutamide (Arm B)
The dose escalation part with INR731 in combination with enzalutamide may be followed by a dose expansion part.
Medicamento: INR731
Oral administration
Medicamento: Androgen deprivation therapy (ADT)
Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care.
Medicamento: Enzalutamide
Oral administration
Experimental: INR731 in combination with abiraterone (Arm C)
Dose escalation of INR731 in combination with abiraterone.
Medicamento: INR731
Oral administration
Medicamento: Androgen deprivation therapy (ADT)
Background therapy. Patients will continue receiving ADT throughout this clinical study as part of the standard of care.
Medicamento: Abiraterone
Oral administration

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Incidence and severity of dose-limiting toxicities (DLTs)
Prazo: 28 days
A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 that occurs within the first 28 days and not clearly and incontrovertibly assessed as due to disease progression, intercurrent illness, concomitant medication, or extraneous causes with the exceptions defined in the study protocol. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
28 days
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Prazo: Up to approximately 24 months
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs and electrocardiograms (ECGs) qualifying and reported as AEs.
Up to approximately 24 months
Frequency of dose interruptions and reductions
Prazo: Up to approximately 24 months
Number of participants with dose interruptions and/or reductions to assess the tolerability.
Up to approximately 24 months
Dose intensity
Prazo: Up to approximately 24 months
Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure.
Up to approximately 24 months

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Overall Response Rate (ORR)
Prazo: Up to approximately 24 months
ORR is defined as proportion of patients achieving a confirmed complete response (CR) or partial response (PR) per Prostate Cancer Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by the investigator.
Up to approximately 24 months
Disease Control Rate (DCR)
Prazo: Up to approximately 24 months
DCR is defined as proportion of patients achieving a CR, PR or stable disease (SD) per PCWG3-modified RECIST v1.1 as assessed by the investigator.
Up to approximately 24 months
Radiological Progression Free Survival (rPFS)
Prazo: Up to approximately 24 months
rPFS is defined as the time from the date of start of treatment to the date of the first documented radiological progression according to PCWG3-modified RECIST v1.1 or death due to any cause.
Up to approximately 24 months
Prostate-Specific Antigen 50% response rate (PSA50 rate)
Prazo: Up to approximately 24 months
PSA50 rate is defined as the proportion of patients who achieve a ≥50% decrease in prostate-specific antigen (PSA) from baseline at any timepoint, confirmed by a second PSA measurement ≥3 weeks later without any PSA progression in between.
Up to approximately 24 months
Area under the plasma concentration-time curve (AUC) of INR731
Prazo: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
Pharmacokinetic (PK) parameters based on plasma concentrations of INR731.
From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
Maximum plasma concentration (Cmax) of INR731
Prazo: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
PK parameters based on plasma concentrations of INR731.
From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
Time to reach maximum plasma concentration (Tmax) of INR731
Prazo: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
PK parameters based on plasma concentrations of INR731.
From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
Trough concentration (Ctrough) of INR731
Prazo: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
PK parameters based on plasma concentrations of INR731.
From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
Plasma concentrations of study drugs
Prazo: From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
Concentration versus time profiles of study drugs.
From pre-dose up to 24 hours after dosing on Cycle 1 Day 1 and Day 15. One cycle = 28 days.
Progression Free Survival (PFS)
Prazo: Up to approximately 24 months
PFS is defined as time from date of start of treatment to the first documented progression (radiological, clinical, or PSA progression) or death from any cause, whichever occurs first.
Up to approximately 24 months

Colaboradores e Investigadores

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

Patrocinador

Novartis Pharmaceuticals

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)

25 de maio de 2026

Conclusão Primária (Estimado)

3 de junho de 2030

Conclusão do estudo (Estimado)

3 de junho de 2030

Datas de inscrição no estudo

Enviado pela primeira vez

30 de abril de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

30 de abril de 2026

Primeira postagem (Real)

6 de maio de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

28 de maio de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

27 de maio de 2026

Última verificação

1 de maio de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • CINR731A12101
  • 2025-524080-20 (Identificador de registro: EU registry (CTIS))

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Descrição do plano IPD

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

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 .

Pesquisar ensaios semelhantes

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

CROs by country

CROs in Taiwan

Condições

Doenças Raras

Intervenções de drogas

Suplementos Alimentares

Patrocinador / Colaboradores

Localizações

Se inscrever