A Phase 1/1b Study of PRT13722 in Participants With Advanced HR+/HER2- Breast Cancer
A Phase 1/1b, First-in-Human, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of PRT13722, a KAT6A Protein Degrader, as Monotherapy and in Combination With Endocrine and Targeted Therapy in Adults With Locally Advanced or Metastatic HR-Positive, HER2-Negative Breast Cancer
This first-in-human, open-label, multicenter study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of PRT13722, an oral KAT6A protein degrader, in adults with locally advanced or metastatic Hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. PRT13722 will be evaluated as monotherapy and in combination with fulvestrant, abemaciclib plus fulvestrant, or imlunestrant to determine recommended dose(s) for expansion (RDE) and evaluate preliminary clinical activity.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a first-in-human, open-label, multicenter, dose-escalation and dose-expansion study of PRT13722, a selective oral KAT6A protein degrader, in adults with locally advanced or metastatic HR-positive, HER2-negative breast cancer. The study will evaluate the safety, tolerability, dose-limiting toxicities, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of PRT13722 administered as monotherapy and in combination with fulvestrant, abemaciclib plus fulvestrant, or imlunestrant to determine recommended dose(s) for expansion and evaluate preliminary clinical activity.
The study is conducted in three parts:
Part 1: Monotherapy dose escalation and backfill cohorts. Part 2: Combination dose-escalation cohorts with fulvestrant, abemaciclib plus fulvestrant, and imlunestrant.
Part 3: Combination dose-expansion cohorts to further evaluate safety and preliminary efficacy at the selected dose levels.
Up to approximately 240 participants are planned for enrollment across the three parts of the study.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Study Contact (Please Do Not Disclose Personal Information)
- Número de teléfono: See Email
- Correo electrónico: clinicaltrials@preludetx.com
Ubicaciones de estudio
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Ohio
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Maumee, Ohio, Estados Unidos, 43537
- Reclutamiento
- Taylor Cancer Research Center
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures.
- histological or cytological diagnosis of locally advanced or metastatic HR-positive/HER2-negative breast cancer
- Disease progression following prior standard therapy and eligible for the assigned study cohort
- Measurable or evaluable disease per RECIST v1.1
- Willingness to provide tumor tissue for biomarker analyses
- Eastern Cooperative Oncology Group performance status of 0-1
- Negative serum or urine pregnancy test and agree to use highly effective contraception or maintain true abstinence.
- Adequate organ function and bone marrow reserves (hematology, renal, and hepatic)
Exclusion Criteria:
- Untreated, symptomatic, or unstable brain metastases
- Symptomatic visceral disease at risk of imminent life-threatening complications
- Uncontrolled infection or significant concurrent medical conditions
- Clinically significant cardiovascular disease or prolonged QT syndrome
- Pregnancy or breastfeeding
- Prior treatment with a KAT6-targeting agent
- Recent anticancer therapy, radiotherapy, or major surgery
- Use of prohibited concomitant medications, including strong CYP3A4 inhibitors or inducers, proton pump inhibitors, P-gp inhibitors or inducers, and breast cancer resistance protein inhibitors
- Participation in another interventional clinical study
- Any condition that would interfere with study participation or evaluation of study results
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: PRT13722 Monotherapy
Participants receive PRT13722 once daily as monotherapy. This arm includes dose-escalation (Part 1A) and backfill cohorts (Part 1B) evaluating PRT13722 in participants with locally advanced or metastatic HR-positive, HER2-negative breast cancer to support the selection of RDE. |
PRT13722 is an investigational oral drug administered once daily at the assigned dose level. |
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Experimental: PRT13722 + Fulvestrant
Participants receive PRT13722 once daily in combination with fulvestrant. This study includes a dose-escalation (Part 2A) in participants with locally advanced or metastatic HR-positive, HER2-negative breast cancer followed by dose-expansion (Part 3A) at the RDE. |
PRT13722 is an investigational oral drug administered once daily at the assigned dose level. Fulvestrant is an approved selective estrogen receptor degrader (SERD) administered on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, then once monthly as an intramuscular injection into the buttocks (gluteal muscle). |
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Experimental: PRT13722 + Abemaciclib + Fulvestrant
Participants receive PRT13722 once daily in combination with abemaciclib and fulvestrant. This study includes a dose-escalation (Part 2B) in participants with locally advanced or metastatic HR-positive, HER2-negative breast cancer followed by dose-expansion (Part 3B) at the RDE. |
PRT13722 is an investigational oral drug administered once daily at the assigned dose level. Fulvestrant is an approved selective estrogen receptor degrader (SERD) administered on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, then once monthly as an intramuscular injection into the buttocks (gluteal muscle). Abemaciclib is an approved oral cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor administered twice daily and used in combination with endocrine therapy for HR-positive, HER2-negative breast cancer. |
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Experimental: PRT13722 + Imlunestrant
Participants receive PRT13722 once daily in combination with imlunestrant. This study includes a dose-escalation (Part 2C) in participants with locally advanced or metastatic HR-positive, HER2-negative breast cancer followed by dose-expansion (Part 3C) at the RDE. |
PRT13722 is an investigational oral drug administered once daily at the assigned dose level. Imlunestrant is an approved oral SERD administered once daily. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Dose limiting toxicity of PRT13722 (Parts 1A and 2)
Periodo de tiempo: Through cycle 1 (28 days)
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Incidence of dose limiting toxicities, defined according to protocol-specified criteria |
Through cycle 1 (28 days)
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Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of PRT13722 as monotherapy and in combination (Parts 1A and 2)
Periodo de tiempo: Through study completion, an average of 2 years
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Safety and tolerability assessed by the number of participants with treatment-emergent adverse events, serious adverse events, adverse events leading to dose modification, treatment interruption, or treatment discontinuation, and clinically significant laboratory abnormalities. Adverse events and selected laboratory abnormalities will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 6.0 |
Through study completion, an average of 2 years
|
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Preliminary Antitumor Activity: Objective Response Rate (Parts 1B and 3)
Periodo de tiempo: Through study completion, an average of 2 years
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Proportion of patients with best overall response of either complete response or partial response, as assessed by the investigator per RECIST v1.1 |
Through study completion, an average of 2 years
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Preliminary Antitumor Activity: Objective Response Rate (Parts 1A and 2)
Periodo de tiempo: Through study completion, an average of 2 years
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Proportion of patients with best overall response of either complete response or partial response, as assessed by the investigator per RECIST v1.1 |
Through study completion, an average of 2 years
|
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Duration of Response
Periodo de tiempo: Through study completion, an average of 2 years
|
Time from first documented response to disease progression as assessed by the investigator per RECIST v1.1, or death, whichever comes first. |
Through study completion, an average of 2 years
|
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Clinical Benefit Response
Periodo de tiempo: Through study completion, an average of 2 years
|
Proportion of patients with a best overall response of complete response, partial response, or durable stable disease (24 weeks or longer), as assessed by the investigator per RECIST v1.1 |
Through study completion, an average of 2 years
|
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Progression-Free Survival
Periodo de tiempo: Through study completion, an average of 2 years
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Time from the date of first dose of investigational product to the date of first documented disease progression, as assessed by the investigator per RECIST v1.1, or death due to any cause |
Through study completion, an average of 2 years
|
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Overall Survival
Periodo de tiempo: Through study completion, an average of 2 years
|
Time from the date of first dose of investigational product to death due to any cause |
Through study completion, an average of 2 years
|
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Incidence of Treatment-Emergent Adverse Events [Safety and tolerability] of PRT13722 as Monotherapy and in Combination (Parts 1B and 3)
Periodo de tiempo: Through study completion, an average of 2 years
|
Safety and tolerability will be evaluated by incidence of adverse events leading to dose modifications, treatment interruptions, treatment discontinuations, and clinically significant laboratory abnormalities graded according to NCI CTCAE, Version 6.0 |
Through study completion, an average of 2 years
|
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Maximum Observed Plasma Concentration (Cmax)
Periodo de tiempo: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
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Maximum observed plasma concentration will be calculated using non-compartmental analysis |
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
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Time To Maximum Concentration (Tmax)
Periodo de tiempo: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
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Time to maximum concentration will be calculated using non-compartmental analysis |
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
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Terminal Elimination Half-life (T1/2)
Periodo de tiempo: Cycle 1 Day 1 (each cycle is 28 days)
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Terminal elimination half-life will be calculated using non-compartmental analysis |
Cycle 1 Day 1 (each cycle is 28 days)
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Area under the plasma concentration versus time curve (AUC)
Periodo de tiempo: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
Area under the plasma concentration-time curve will be calculated using non-compartmental analysis |
Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
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Steady State Trough Concentrations
Periodo de tiempo: Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
Steady state trough concentrations will be calculated using non-compartmental analysis |
Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle is 28 days)
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
- Cáncer de mama
- Cáncer de mama metastásico
- Fulvestrant
- Abemaciclib
- Cáncer de mama HER2 negativo
- Cáncer de mama localmente avanzado
- Cáncer de mama HR positivo
- HR+/HER2- Cáncer de mama
- Cáncer de mama con receptores hormonales positivos
- Imlunestrant
- Locally Advanced or Metastatic HR+/HER2- Breast Cancer
- PRT13722
- KAT6A
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Neoplasias
- Enfermedades de la piel
- Enfermedades de los senos
- Enfermedades de la piel y del tejido conectivo
- Neoplasias de mama
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Compuestos policíclicos
- Esteroides
- Compuestos de anillo fusionado
- Estradiol
- Estreness
- Estranos
- Congéneres de estradiol
- Hormonas esteroides gonadal
- Hormonas gonadales
- Fulvestrant
- abemaciclib
- Imlunestrant
Otros números de identificación del estudio
- PRT13722-01
- 2026-527825-37-00 (Ctis)
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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