TROPION-Breast05: a randomized phase III study of Dato-DXd with or without durvalumab versus chemotherapy plus pembrolizumab in patients with PD-L1-high locally recurrent inoperable or metastatic triple-negative breast cancer
- Author(s)
- Schmid, P; Oliveira, M; O'Shaughnessy, J; Cristofanilli, M; Graff, SL; Im, SA; Loi, S; Saji, S; Wang, S; Cescon, DW; Hovey, T; Nawrot, A; Tse, K; Vukovic, P; Curigliano, G;
- Journal Title
- Therapeutic Advances in Medical Oncology
- Publication Type
- Research article
- Abstract
- BACKGROUND: Standard of care (SoC) for patients with advanced triple-negative breast cancer (TNBC) whose tumors express PD-L1 (combined positive score ⩾ 10) is chemotherapy plus anti-PD-(L)1 inhibitors; however, prognosis and survival for most patients is poor. Datopotamab deruxtecan (Dato-DXd), a novel antibody-drug conjugate comprising a humanized anti-TROP2 IgG1 monoclonal antibody conjugated to a potent topoisomerase I inhibitor payload via a plasma-stable, cleavable, tetrapeptide-based linker, has shown preliminary activity as mono or combination therapy in advanced/metastatic TNBC. OBJECTIVES: TROPION-Breast05 is an ongoing randomized, open-label, multicenter phase III study. The primary objective is to demonstrate the superiority of Dato-DXd in combination with durvalumab (an anti-PD-L1 antibody) versus SoC treatment in patients with PD-L1-high locally recurrent inoperable or metastatic TNBC. METHODS AND DESIGN: Patients (⩾18 years) will be randomized 1:1 to receive Dato-DXd (6 mg/kg intravenously (IV) every 3 weeks (Q3W)) plus durvalumab (1120 mg IV Q3W) or investigator's choice of chemotherapy (ICC; paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) plus pembrolizumab (200 mg IV Q3W). In selected countries, patients will also be randomized (1:1:1) to a third arm of Dato-DXd monotherapy. The primary study endpoint is progression-free survival (PFS) per blinded independent central review (Dato-DXd plus durvalumab arm vs ICC plus pembrolizumab arm). Overall survival is a key secondary endpoint; other secondary endpoints include PFS (investigator-assessed), objective response rate, duration of response, clinical benefit rate at Week 24 (all assessed in the Dato-DXd plus durvalumab arm vs ICC plus pembrolizumab arm), patient-reported outcomes, and safety. ETHICS: The study is approved by independent ethics committees or institutional review boards at each study site. All patients will provide written informed consent. DISCUSSION: TROPION-Breast05 will assess the potential role of Dato-DXd with or without durvalumab in patients with PD-L1-high advanced or metastatic TNBC. The findings of this trial could lead to a new treatment option for these patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06103864 (Date of registration: 27 October 2023).; TROPION-Breast05: A clinical study comparing datopotamab deruxtecan (Dato-DXd), alone or in combination with durvalumab, versus standard-of-care treatment in people with triple-negative breast cancer (TNBC) with cancer cells that express PD-L1 and whose cancer cannot be removed by surgery or has spread to other parts of the body. Standard treatment for people with TNBC that cannot be removed with surgery or has spread to other parts of the body and whose cancer cells express a protein called PD-L1 is chemotherapy plus anti-PD-(L)1 inhibitors. However, additional treatment options are needed to improve treatment outcomes and minimize side effects. Dato-DXd, an antibody-drug conjugate (ADC), consists of an antibody (datopotamab) linked to an anti-cancer drug (deruxtecan). The antibody attaches to a protein found on the surface of breast cancer cells called TROP2. The antibody is then taken inside the cancer cells, the anti-cancer drug is released, and the cells are killed. By releasing the anti-cancer drug inside the cell, the treatment is directed to the cancer site with the goal of minimizing side effects. In a study called TROPION-PanTumor01, 40% of people with TNBC who received Dato-DXd (and who had not previously received ADCs) had a reduction in their tumor size of at least 30%. These results were promising and it is thought that combining Dato-DXd with a PD-L1 inhibitor may make cancer cells more susceptible to being targeted by the body’s immune system. In another study called BEGONIA, Dato-DXd was evaluated in combination with durvalumab, which blocks the PD-1/PD-L1 interaction. In people with TNBC, treatment with Dato-DXd and durvalumab resulted in a decrease in tumor size of at least 30% in 79% of people. The safety profile of Dato-DXd and durvalumab was tolerable and manageable; the most common D-DXd side effects were nausea and mouth sores, known as stomatitis. Based on data from TROPION-PanTumor01 and BEGONIA, the phase III TROPION-Breast05 will compare Dato-DXd alone and in combination with durvalumab vs standard-of-care treatment for people with TNBC whose cancer cells express PD-L1, and whose cancer cannot be removed by surgery, or their cancer has spread to other parts of the body.; eng
- Publisher
- Sage
- Keywords
- antibody-drug conjugate; datopotamab deruxtecan; durvalumab; immunotherapy; programmed cell death ligand-1; triple-negative breast cancer; trophoblast cell-surface antigen 2
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1177/17588359251327992
- Open Access at Publisher's Site
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Creation Date: 2025-07-08 04:31:23
Last Modified: 2025-07-08 04:32:02