Datopotamab deruxtecan (Dato-DXd), a TROP2 directed DXd antibody drug conjugate, was administered to the first patient with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (mTNBC) not eligible to receive PD-1/PD-L1 inhibitor therapy, in the TROPION-Breast02 (NCT05374512), according to a press release by Daiichi Sankyo.1
Trial Name: A Phase 3, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) Versus Investigator's Choice of Chemotherapy in Patients Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy in First-line Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION Breast02)
Completion Date: December 3, 2025
Sponsors: AstraZeneca and Daiichi Sankyo, Inc.
Recruitment Contact: email@example.com or
TROPION-Breast02 will build on phase 1 data from TROPION-PanTumor01 trial (NCT03401385), in which Dato-DXd demonstrating promising responses in patients with mTNBC.1,2
In the mTNBC cohort of 44 patients in TROPION-PanTumor01, the objective response rate by blinded independent central review (BICR) was 34% which included complete responses (CRs) or partial responses (PRs) in 32% of patients, and stable disease (SD) in 39%. Notably, 5% were not evaluable for response, and 8 patients had progressive disease (PD). The disease control rate (DCR) overall was 77%. There was 1 CR/PR pending confirmation at the time of data cutoff.2
A subset of patients (n = 27) did not receive prior treatment with an antibody drug conjugate, and among these patients, the ORR was 53% with Dato-DXd. Confirmed CRs and PRS were observed in 48%, and SD was observed in 33%. Four percent of patients in the subset were not evaluable for response, and 15% of patients had PD. A CR/PR was also pending confirmation in the subset at the time of data cutoff.
The median duration of response was not reached (range, 2.7-7.4+ months) in the analysis.
The most frequent treatment-emergent adverse events (TEAEs) observed with Dato-DXd in TROPION-PanTumor01 were nausea, stomatitis, vomiting, and fatigue. There were dose reductions due to AEs in 18% of patients, and 14% of patients experienced treatment interruption due to AE. There was 1 treatment discontinuation as a result AEs, but no AE-related fatalities.
"Patients with metastatic triple negative breast cancer who are not able to receive PD-1/PD-L1 inhibitor treatment often experience recurrence following chemotherapy, so additional options in the first-line treatment setting are needed," said Gilles Gallant, BPharm, PhD, FOPQ, senior vice president, global head, Oncology Development, Oncology R&D, Daiichi Sankyo, in a press release.1
TROPION-Breast02 is a phase 3, open-label, randomized study of Dato-DXd versus investigator's choice of chemotherapy in patients who are not candidates for PD-1/PD-L1 inhibitor therapy in first-line locally recurrent inoperable or mTNBC. The goal of the study is to assess the safety and efficacy of datopotamab deruxtecan with the coprimary end point of progression-free survival (PFS) and overall survival (OS).
The study will include 600 patients. In addition to PFS and OS, the study will evaluate objective response, duration of response, investigator-assessed PFS, time to deterioration, time to first subsequent therapy, PFS2, pharmacokinetics, the immunogenicity of Dato-DXd, and safety as secondary end points.
To be eligible for inclusion in the study, patients are required to be at least 18 years of age at the time of screening with histologically- or cytologically-documented locally recurrent inoperable or mTNBC. Patients must have not received prior chemotherapy, be ineligible for PD-1/PD-L1 therapy, and not be pregnant. Women must be at least 1 year post-menopausal before enrolling. Requirements also included showing measurable disease per RECIST v1.1, an ECOG performance score of 0 or 1, adequate organ and bone marrow function, and adequate organ and bone marrow function, and minimum life expectancy of 12 months.
"Initial results of datopotamab deruxtecan in patients with pretreated metastatic triple negative breast cancer, a group with a significant unmet need, have been encouraging," said Cristian Massacesi, MD, chief medical officer and Oncology chief development officer, AstraZeneca, in a statement. "We are building on these early results by moving forward with the TROPION-Breast02 trial, the second pivotal trial of datopotamab deruxtecan in breast cancer, to determine if this antibody drug conjugate may potentially be used earlier in the treatment of metastatic triple negative breast cancer."
1. TROPION-Breast02 phase 3 trial of datopotamab deruxtecan initiated in patients with previously untreated metastatic triple negative breast cancer. News release. Daiichi Sankyo. June 13, 2022. Accessed June 14, 2022. https://bit.ly/39tRCGT
2. Krop I, Juric D, Shimizu T, et al. Datopotamab deruxtecan (Dato-DXd) in advanced/metastatic HER2 negative breast cancer: triple negative breast cancer results from the phase 1 TROPION-PanTumor01 study. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract GS1-05.