Dr Jeselsohn on Enrollment Criteria For the VERITAC-2 Trial in ER+ Breast Cancer

Rinath M. Jeselsohn, MD, physician, director, ER+ Translational Discovery Research, Dana-Farber Cancer Institute; assistant professor, medicine, Harvard Medical School, discusses enrollment criteria for the phase 3 VERITAC-2 trial (NCT05654623), as well as the potential clinical implications of this research for patients with advanced estrogen receptor (ER)–positive/HER2-negative metastatic breast cancer.

The randomized VERITAC-2 trial is investigating the efficacy of the proteolysis targeting chimera vepdegestrant (ARV-471) compared with fulvestrant (Faslodex) in patients with advanced ER+ metastatic breast cancer. This trial is enrolling patients who have received 1 prior line of endocrine therapy alongside a CDK4/6 inhibitor. Patients are also permitted to have received 1 additional prior line of endocrine therapy. Patients need to have received their most recent endocrine therapy for at least 6 months prior to disease progression.

Notably, part B of the phase 1/2 VERITAC trial (NCT04072952) also required patients to have evidence of disease stability with their most recent line of endocrine therapy in the locally advanced or metastatic setting, Jeselsohn says. Since patients in VERITAC-2 may be randomly assigned to receive fulvestrant, those who have received prior fulvestrant will be excluded, Jeselsohn notes. Patients will also be excluded if they have previously received vepdegestrant, elacestrant, or mTOR, PI3K, AKT pathway, and PARP inhibitors in any setting.

The primary end point of VERITAC-2 is progression-free survival. Key secondary end points include overall survival, overall response rate, duration of response, clinical benefit rate, and safety.

For patients with endocrine-sensitive breast cancer, defined as those who have received endocrine therapy plus a CDK4/6 inhibitor for at least 12 months, the option of a single-agent endocrine therapy is appealing, Jeselsohn says. Additionally, safety data from VERITAC indicate that vepdegestrant was well tolerated, according to Jeselsohn. Single-agent vepdegestrant may be an effective treatment option for subsets of patients with advanced metastatic breast cancer, particularly those with ESR1 mutations, Jeselsohn emphasizes. Future research is needed to determine whether the efficacy of this agent is enhanced when used in combination with other targeted treatments, Jeselsohn explains. Vepdegestrant-based combinations may be more effective than the currently available combinations for this patient population, Jeselsohn concludes.