ReclutandoNCT06827236Registro de ClinicalTrials.gov

A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer

Locally Advanced Breast Cancer · Unresectable Breast Carcinoma · Metastatic Breast Cancer

Pregúntale a WCR sobre este estudio Registro oficial ↗

LO ESENCIAL

De qué trata este estudio

El registro indica que este estudio recluta participantes. La disponibilidad puede variar por centro.

Tipo de estudio: De intervención
Fase: Fase 1 / Fase 2
Rango de edad: 18 años - No especificado
Sexo admitido: Todos los sexos
Voluntarios sanos: No aceptados
Participantes: 380 Estimado

Estos son puntos de partida, no una decisión de elegibilidad. El equipo debe revisar todos los requisitos.

Las explicaciones y la navegación están en español. Los textos proporcionados por el registro, incluidos títulos, resúmenes y criterios, se conservan en su idioma original. Puedes pedir orientación en español a WCR.

Acerca de la investigación

This is a Phase I/II, multi-site, open-label, two-part study designed to evaluate the efficacy, safety, optimized dose and contribution of components of BNT323 (also known as trastuzumab pamirtecan and DB-1303) in combination with BNT327 (also known as pumitamig and PM8002) in participants with hormone receptor-positive (HR+) or hormone receptor-negative (HR-), Human epidermal growth factor receptor (HER)2-positive, HER2-low (immunohistochemistry \[IHC\] 1+ or IHC 2+/in situ hybridization -), HER2-ultralow (IHC 0, with membrane staining) or HER2-null breast cancer (BC), or triple-negative breast cancer (TNBC).

Leer la descripción completa

The study consists of two parts:

Part 1 - Dose escalation: In this part of the study, participants with histologically confirmed, chemotherapy-pretreated advanced HR+, HER2-low or HER2-ultralow BC will receive BNT323 in combination with BNT327 (BNT323 + BNT327) in a dose escalation design. This will define the recommended Phase 2 dose (RP2D) for the BNT323 + BNT327 combination therapy.
Part 2 - Dose optimization and exploratory cohorts: This part of the study will be an expansion phase, aiming to evaluate the efficacy and safety of the optimal dose combination and providing a more robust comparison against the other treatments. It will start once the enrollment in Part 1 is completed and the sponsor in conjunction with the Safety Review Committee has assessed available Part 1 efficacy and safety data. Part 2 of the study will have four cohorts, i.e., Cohorts 1 (dose optimization cohort), and Cohorts 2, 3, and 4 (exploratory cohorts). Recruitment to Cohorts 2, 3, and 4 will begin with RP2D from Part 1 and in parallel to randomization in Cohort 1.

Randomization is planned for Cohort 1 in Part 2, i.e., participants will be randomized in 2:2:1:1 ratio into one of the four arms (Arms 1-4). No randomization is planned for any other cohort in Part 2.

¿Quién podría participar?

La lista siguiente contiene el texto del patrocinador. Puede incluir condiciones, tratamientos previos, resultados de pruebas y otros requisitos. Aparecer en tu búsqueda no significa que califiques.

Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):

Have pathologically documented BC that:

Is locally advanced, unresectable or metastatic.
Has a confirmed HER2 status as determined by the local laboratory as standard of care testing prior to study screening (Part 1, Part 2 Cohorts 2 and 4) or the central laboratory (Part 2, Cohorts 1 and 3) from the most recently collected pre-randomization tumor sample.
Has a documented history of HER2 expression consistent with the subgroup definitions (i.e., HER2-low, HER2-ultralow, HER2-null, HER2-positive, or TNBC) as per current American Society of Clinical Oncology/College of American Pathologists guidelines.
Have measurable disease defined by RECIST v1.1.
Has left ventricular ejection fraction ≥55% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.

Key Exclusion Criteria:

Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.
Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugates with topoisomerase I inhibitor payloads such as trastuzumab deruxtecan.
Have received any of the following therapies or drugs prior to the initiation of the study:

Participants who have received prior treatment with BNT323.
Participants who received prior treatment with a programmed death-ligand 1 (PD-L1) / vascular endothelial growth factor (VEGF) bispecific antibody. Note: Prior treatment with programmed death 1 (PD-1)/VEGF bispecific antibodies, PD-1/PD-L1 inhibitors or anti-VEGF therapies are permitted.
Have received other systemic immunostimulatory agents or immunosuppressive therapies (such as interferon-α, interleukin-2, or methotrexate) within 4 weeks prior to the initiation of study treatment or are within five half-lives of the treatment drug (whichever is longer). Exception: excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 3 weeks prior to the initiation of study treatment.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Entiende la evaluación inicial

Tratamiento, grupos y participación

El registro puede describir tratamientos y duración sin incluir un calendario completo. Pide al equipo las visitas, procedimientos, riesgos, costos y alternativas. Mantén tu atención habitual salvo que tu médico te indique un cambio.

Asignación: Asignación al azar
Enmascaramiento: Sin enmascaramiento

Part1 - BNT323 + BNT327 combination therapy

Escalating dose levels (DLs) of BNT323 and BNT327 to define RP2D. Six DLs are planned, i.e., DL0-1, DL1-1, DL2-1, DL0-0, DL1-0, DL2-0, a combination of three different DLs for BNT323 (DL0, DL1, and DL2) and two DLs for BNT327 (DL0 and DL1).

Drug: BNT323 · Drug: BNT327

Part 2 Cohort 1 - Arm 1 - RP2D of BNT323 + BNT327

No informado en este registro.

Drug: BNT323 · Drug: BNT327

Part 2 Cohort 1 - Arm 2 - BNT323 + BNT327

No informado en este registro.

Drug: BNT323 · Drug: BNT327

Part 2 Cohort 1 - Arm 3 - BNT323 monotherapy

BNT323 monotherapy at a fixed dose

Drug: BNT323

Part 2 Cohort 1 - Arm 4 - BNT327 monotherapy

BNT327 monotherapy at a fixed dose

Drug: BNT327

Part 2 Cohort 2 - RP2D of BNT323 + BNT327

No informado en este registro.

Drug: BNT323 · Drug: BNT327

Part 2 Cohort 3 - RP2D of BNT323 + BNT327

No informado en este registro.

Drug: BNT323 · Drug: BNT327

Part 2 Cohort 4 - RP2D of BNT323 + BNT327

No informado en este registro.

Drug: BNT323 · Drug: BNT327

BNT323 DRUG

Intravenous infusion

BNT327 DRUG

Intravenous infusion

Prepara tus preguntas

Qué evalúan los investigadores

Estas medidas indican qué se estudia. No prueban que un tratamiento funcione.

Medidas principales

Part 1 - Occurrence of dose limiting toxicities (DLTs)

Plazo: During the DLT evaluation period (Cycle 1), i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days

By dose level.

Occurrence of Treatment-emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade ≥3 TEAEs, and treatment-related SAEs

Plazo: From the time of initiation of the first dose of IMP to 90 days after the last IMP dose

In Part 1 by dose level. In Part 2 by cohort and arm.

Occurrence of dose interruption, reduction, and discontinuation due to TEAEs

Plazo: From the time of initiation of the first dose of IMP to 90 days after the last IMP dose

In Part 1 by dose level. In Part 2 by cohort and arm.

Part 2 - Objective response rate (ORR)