Dr Vahdat on the Design of a Phase 2 Trial Evaluating Copper Depletion in High-Risk TNBC

“We have a number of exploratory end points, which are geared to help us understand: What are the right tumors for copper depletion? Probably not all tumors are dependent on it, and [we want to determine] how to optimize copper depletion.”

Linda T. Vahdat, MD, MBA, section chief of Medical Oncology and interim section chief of Hematology at Dartmouth Health, as well as a professor of medicine at the Dartmouth College Geisel School of Medicine, detailed the design of a phase 2 trial (NCT06134375) evaluating whether copper depletion can effectively prevent metastasis in patients with high-risk triple-negative breast cancer (TNBC).

The study is enrolling patients with triple-negative breast cancer patients who have completed chemotherapy and surgery but continue to exhibit significant amounts of residual disease. Since this patient group faces an exceptionally high risk of the tumor returning, the trial aims to establish a definitive strategy for managing their care and improving long-term outcomes, according to Vahdat.

The trial is divided into 2 parts: a phase 1b lead-in portion followed by a randomized phase 2 portion. In the phase 1b portion, all patients will receive at least 1 cycle of the immunotherapy pembrolizumab (Keytruda) in combination with capecitabine (Xeloda) and the copper depletion compound tetrathiomolybdate (Coprexa). In the phase 2 portion, patients will be randomly assigned to receive the standard regimen of capecitabine with or without immunotherapy, or that same treatment supplemented by tetrathiomolybdate.

As of December 2025, the trial has been open for 1 year and is accruing patients successfully, with plans to launch the randomized portion in June 2026, Vahdat said. Due to successful extramural funding, the study has expanded to include additional sites, she noted. Vahdat emphasized that the inclusion of multiple sites is a strategic choice intended to accelerate the completion of the trial, stating that additional funding may allow for further expansion to even more locations.

Ultimately, the trial's success will be measured by its primary end point of distant relapse-free survival, alongside secondary metrics, such as overall survival and patient-reported outcomes. The research team is also tracking several critical biomarkers, including bone marrow–derived endothelial progenitor cells, circulating tumor DNA, and lysyl oxidase, to monitor the biological effects of the treatment. Vahdat concluded that these efforts are essential for identifying which tumors are dependent on copper, thereby allowing for the optimization of copper depletion therapy for the right patients.