Adjuvant Tirzepatide Plus Standard of Care Endocrine Therapy in Patients With Obesity or Overweight Who Have Hormone Receptor-positive, HER2-negative, Node-positive Early Breast Cancer, With Molecular Residual Disease (MRD), as Determined by Circulating Tumor DNA (ctDNA)
This trial aims to asses if tirzepatide-induced weight loss will lead to metabolic and hormonal changes in hormone receptor-positive (HR+), human epidermal growth factor receptor-negative (HER2-), node-positive (N+) high risk early breast cancer patients with obesity or overweight, inhibiting the growth and survival of micrometastatic disease and leading to clearance of tumor-informed circulating tumor DNA (ctDNA) and freedom from the development of metastatic disease.
• Female or male patients ≥18 years of age
• Have a diagnosis of node-positive, hormone receptor-positive (ER+ \> 10%), and HER2-negative breast cancer within the past 15 years per the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
∙ If patients have synchronous bilateral ER+ breast cancers, tissue from both primary cancers should be submitted for next-generation sequencing (NGS) to inform ctDNA testing
‣ Patients with multifocal/multicentric cancers are eligible and the largest focus of cancer should be submitted for NGS evaluation. If tested, all tumor foci must meet have ER \> 10%
‣ For patients who received neoadjuvant therapy and have discordant hormone receptor and/or HER2 results between the diagnostic biopsy (pre-treatment) and the surgical pathology (post-neoadjuvant treatment), the hormone receptor status and HER2 status of the post-treatment specimen will determine eligibility
• Overweight or obesity defined as body mass index (BMI) \> 27 kg/m2
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Have received at least 1 year of or having completed standard neo/adjuvant endocrine therapy. If adjuvant cyclin dependent kinase (CDK) 4/6 inhibitor therapy was prescribed, patients must have completed this therapy
• Positive ctDNA blood test as determined by the Haystack Oncology Haystack MRD tumor-informed ctDNA assay
• Patients must have formalin-fixed paraffin-embedded (FFPE) tissue from the primary tumor available for submission to Haystack Oncology to perform whole genome sequencing (WGS) to build customized mutation panel to monitor for plasma ctDNA
• No clinical evidence of metastatic breast cancer found on history, physical examination, complete blood count (CBC), comprehensive metabolic panel (CMP), and radiologic imaging following a finding of positive ctDNA
• Have adequate hematologic function, defined by:
∙ Absolute neutrophil count (ANC) \>1500/µL
‣ Platelet count ≥100,000/ µL
‣ Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
⁃ Have adequate liver function, defined by:
• Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤3 x the upper limit of normal (ULN)
∙ Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels \>1.5 × ULN
⁃ Have adequate renal function, defined by:
⁃ a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥30 mL/min
⁃ Patients must be accessible for treatment and follow-up
⁃ All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry