Resumen

Este es un estudio internacional de fase III, aleatorizado, abierto, de 3 brazos y multicéntrico, que evalúa la eficacia y seguridad de Dato-DXd con o sin durvalumab en comparación con la quimioterapia a elección del investigador en combinación con pembrolizumab en participantes con cáncer de mama triple negativo (TNBC) localmente recurrente inoperable o metastásico con PD-L1 positivo.

Descripción detallada

El objetivo primario del estudio es demostrar la superioridad de Dato-DXd + durvalumab frente a la quimioterapia a elección del investigador (ICC) + pembrolizumab mediante la evaluación de la supervivencia libre de progresión (SLP) según la revisión central independiente ciega (BICR) en participantes con TNBC localmente recurrente inoperable o metastásico con PD-L1 positivo. El estudio estará estratificado según la localización geográfica (EE. UU./Canadá/Europa frente a países con inscripción en monoterapia de Dato-DXd frente a resto del mundo), el historial de intervalo libre de enfermedad (ILE) (de novo frente a ILE previo de 6 a 12 meses frente a ILE previo > 12 meses) y el tratamiento previo con anti-PD-1/PD-L1 para TNBC en estadio temprano (sí frente a no). Este estudio tiene como objetivo determinar si Dato-DXd con durvalumab permite que los pacientes vivan más tiempo sin que su cáncer de mama empeore, o simplemente vivan más tiempo, en comparación con los pacientes que reciben quimioterapia estándar y pembrolizumab. El estudio también evalúa cómo el tratamiento y el cáncer de mama afectan la calidad de vida de los pacientes.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC, as defined by the ASCO-CAP guidelines.
ECOG PS 0 or 1.
Participants are expected to provide an FFPE tumour sample collected from a locally recurrent inoperable or metastatic tumour. Alternatively, an archival FFPE tumour sample can be submitted; it must have been collected ≤ 3 years prior to the participant signing informed consent (screening start).
PD-L1 positive TNBC based on results from an appropriately validated investigational PD-L1 (22C3) assay (CPS ≥ 10) from a sponsor designated central laboratory.
No prior chemotherapy or other systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer.
\- Patients with recurrent disease will be eligible if they have completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months have elapsed between completion of treatment with curative intent and the first documented recurrence.
Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin).
Measurable disease as per RECIST 1.1.
Adequate bone marrow reserve and organ function.
Male and female participants of childbearing potential must agree to use protocol-specified method(s) of contraception.

Criterios de exclusión

As judged by investigator, any evidence of diseases (such as severe or uncontrolled medical conditions including systemic diseases, uncontrolled hypertension, serious gastrointestinal conditions associated with diarrhoea, chronic diverticulitis or previous complicated diverticulitis, history of allogeneic organ transplant, and active bleeding diseases, ongoing and active infection, significant cardiac conditions, substance abuse, psychiatric illness/social situation or psychological conditions) which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before Cycle 1 Day 1 and of low potential risk for recurrence.
Participants with a history of previously treated neoplastic spinal cord compression or treated, clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy.
\- Participants with treated clinically inactive brain metastases that are no longer symptomatic, who require no treatment with corticosteroids or anticonvulsants, may be included in the study if they have recovered from acute toxic effects of radiotherapy.
Uncontrolled infection requiring IV antibiotics, antivirals or antifungals.
Active or uncontrolled hepatitis B or C virus infection.
Known HIV infection that is not well controlled.
Uncontrolled or significant cardiac disease.
History of non-infectious ILD/pneumonitis (including radiation pneumonitis) that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
Clinically severe pulmonary function compromise.
Clinically significant corneal disease.
Active or prior documented autoimmune or inflammatory disorders.
Prior exposure to any treatment including ADC containing a chemotherapeutic agent targeting topoisomerase I and TROP2-targeted therapy.
Any concurrent anti-cancer treatment.
Participants with a known severe hypersensitivity to PD-1/PD-L1 inhibitors or Dato-DXd.
Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Dato-DXd

Durvalumab

Paclitaxel

Nab-paclitaxel

Gemcitabine

Carboplatin

Pembrolizumab

Ubicaciones

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Patrocinadores

Contactos

AstraZeneca Clinical Study Information Center

AstraZeneca Breast Cancer Study Locator Service