A Phase III Study of Dato-DXd With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy in Combination With Pembrolizumab in Patients With PD-L1 Positive Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer
Status and phase
Conditions
Treatments
Details and patient eligibility
About
This is a Phase III, randomised, open-label, 3-arm, multicentre, international study assessing the efficacy and safety of Dato-DXd with or without durvalumab compared with investigator's choice chemotherapy in combination with pembrolizumab in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.
Full description
The primary objective of the study is to demonstrate superiority of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS as assessed by BICR in participants with PD-L1 positive locally recurrent inoperable or metastatic TNBC.
The study will be stratified based on geographic location (US/Canada/Europe vs. Dato-DXd monotherapy enrolling countries vs. rest of world), disease-free interval (DFI) history (de novo vs. prior DFI 6 to 12 months vs. prior DFI > 12 months), and prior PD-1/PD-L1 treatment for early stage TNBC (yes vs. no).
This study aims to see if Dato-DXd with durvalumab allows patients to live longer without their breast cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy and pembrolizumab. This study is also looking to see how the treatment and the breast cancer affects patients' quality of life.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Key Inclusion Criteria
-
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. If no such sample is available, 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.
Key Exclusion Criteria
-
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 3 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.
-
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.
Trial design
Primary purpose
Allocation
Interventional model
Masking
625 participants in 3 patient groups
Trial contacts and locations
Loading...
Central trial contact
AstraZeneca Clinical Study Information Center; AstraZeneca Breast Cancer Study Locator Service
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal