Recruiting

Phase 3

Dato-DXd & DurvalumabA 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 (TROPION-Breast05)

Sponsor:

AstraZeneca

Code:

NCT06103864

Conditions

Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Dato-DXd

Durvalumab

Paclitaxel

Nab-paclitaxel

Gemcitabine

Study Details

Brief summary:

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.

Conditions

Breast Cancer

Study ID

NCT06103864

Start date

Nov 23, 2023

Status verified date

Aug, 2026

Completion date

Sep 30, 2030

Anticipated

Primary completion date

Jul 28, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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. 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.

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 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.

Study Design

Enrollment

625 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dato-DXd + durvalumab

Arm 1: Dato-DXd + durvalumab

active comparator: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab

Arm 2: Investigator's Choice of Chemotherapy (ICC) in combination with pembrolizumab (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin)

experimental: Dato-DXd

Arm 3: Dato-DXd

Interventions

Dato-DXd

Provided in 100mg vials. IV infusion. Experimental drug.

Durvalumab

Provided in 500mg vials. IV infusion. Experimental drug.

Paclitaxel