The UNITY study is a prospective, single-arm, single-center, Phase II clinical trial conducted by Fudan University Shanghai Cancer Center. It aims to evaluate the efficacy and safety of Trastuzumab Deruxtecan (T-DXd) combined with ivonescimab in patients with hormone receptor-positive (HR+), HER2-negative recurrent or metastatic breast cancer.
Approximately 53 patients will be enrolled. Eligible participants must have histologically confirmed advanced HR-positive breast cancer with HER2-low or HER2-ultralow expression. They must have experienced recurrence, metastasis, or disease progression after prior treatment with a CDK4/6 inhibitor (including in the adjuvant setting) and have received at most one line of systemic chemotherapy for advanced disease. The study permits the enrollment of patients with central nervous system (CNS) metastases.
The primary endpoint is the Overall Response Rate (ORR). Key secondary endpoints include Clinical Benefit Rate (CBR), Overall Survival (OS), Progression-Free Survival (PFS), safety, and patient-reported quality of life (assessed using EORTC QLQ-C30 and QLQ-BR23). Exploratory endpoints will involve the analysis of biomarkers from tumor and blood samples, as well as PAM50 molecular subtyping and its correlation with survival outcomes.
This study seeks to explore the efficacy and safety of Trastuzumab Deruxtecan in combination with ivonescimab for patients with HR-positive, HER2-negative recurrent or metastatic breast cancer, with a particular focus on the subpopulation with CNS metastases.
Age ≥ 18 years, any gender.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
Histologically or cytologically confirmed Hormone Receptor-positive (HR+) and Human Epidermal Growth Factor Receptor 2 (HER2)-low or HER2-ultralow breast cancer, with evidence of locally recurrent or metastatic disease that is not amenable to curative-intent surgery or radiation therapy.
HR positivity is defined as Estrogen Receptor (ER) positive (≥1% positive cells) and/or Progesterone Receptor (PR) positive (≥1% positive cells).
Confirmed leptomeningeal metastases by Magnetic Resonance Imaging (MRI) or lumbar puncture.
Prior treatment with anti-PD-1/PD-L1 or anti-VEGF agents, unless both of the following conditions are met: (1) The patient did not experience disease progression during treatment with the anti-PD-1/PD-L1 or anti-VEGF agent; and (2) The time from the last dose of the anti-PD-1/PD-L1 or anti-VEGF agent to the time of recurrence or disease progression is ≥ 3 months.
Presence of third-space fluid accumulation (e.g., massive pleural or peritoneal effusion) that cannot be controlled by drainage or other methods.
Receipt of whole-brain radiotherapy, chemotherapy, targeted biologic therapy, immunotherapy, surgery, or endocrine therapy within 2 weeks prior to the first dose of study drug. Bone-modifying agents for the treatment of bone metastases or prevention of osteoporosis are permitted.
Single group
Trastuzumab Deruxtecan and ivonescimab
Drug* Trastuzumab Deruxtecan (T-DXd): Administered at a dose of 5.4 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle. * Ivonescimab: Administered at a dose of 20 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle. Treatment for both agents will continue until disease progression or unacceptable toxicity.
ORR
ORR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response) or PR (partial response) per RECIST v1.1 .Time from randomization to disease progression or death, assessed by RECIST v1.1.
PFS
PFS is the time from the date of first dose until the date of objective radiographic disease progression or death (by any cause in the absence of progression).
OS
OS is the time from the date of frst dose until the date of death by any cause.
Clinical Benefit Rate
CBR is defined as the percentage of patients who achieve a Complete Response (CR), a Partial Response (PR), or have Stable Disease (SD) lasting for at least 24 weeks.
Safety assessed by NCI-CTCAE v5.0
Safety and tolerability will be evaluated by monitoring and recording all adverse events (AEs). The severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. AEs are defined as any adverse event that starts or worsens in severity on or after the first dose of study treatment.
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