Organoid-Guided Functional Precision Therapy Versus Treatment of Physician's Choice in Previously Treated HER2-negative Advanced Breast Cancer: A Phase II, Multicenter, Open-label, Randomized Controlled Trial
This is a phase II, multicenter, open-label, randomized controlled trial to compare the efficacy of organoid-guided treatment (OGT) to treatment of physician's choice (TPC) in previously treated, HER2-negative locally advanced or metastatic breast cancer. The study will seek to provide evidence for utilizing patient-derived organoid (PDO) model to personalize treatment strategies and inform clinical care for advanced breast cancer. Subjects randomized to the OGT group will undergo PDO generation and receive treatment dictated by subsequent PDO drug sensitivity screening. Subjects randomized to the TPC group will receive empirical therapy as selected by the treating physician.
• Must be competent and able to comprehend, sign, and date a written informed consent form (ICF) before performance of any study-specific procedures or tests.
• Men or women ≥18 years old.
• Pathologically documented unresectable locally advanced or metastatic breast cancer that:
‣ 1 Confirmed as HER2-negative status, defined as IHC 0, IHC 1+, or IHC 2+/ISH- according to American Society of Clinical Oncology College of American Pathologists (ASCO/CAP) guidelines evaluated at a local laboratory.
‣ 2 Is HR-positive or HR-negative. Positive for estrogen receptor or progesterone receptor if a finding of ≥1% of tumor cell nuclei is immunoreactive according to ASCO/CAP guidelines.
‣ 3 Has been treated with at least 1 prior line of systemic therapy in the advanced or metastatic setting. If \>10% ER expression, the subject should have been treated with a CDK4/6 inhibitor. If recurrence occurred within 6 months of adjuvant chemotherapy, adjuvant therapy would count as 1 line of systemic therapy. If recurrence occurred within 12 months of adjuvant CDK4/6 inhibitor and endocrine therapy, adjuvant therapy would count as 1 line of systemic therapy.
• Documented radiologic progression (during or after most recent treatment).
• Presence of at least 1 measurable lesion based on computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• All subjects must have a recent tumor sample after the most recent treatment regimen or agree to undergo a tissue biopsy prior to randomization.
• No visceral crisis.
• Life expectancy of ≥ 6 months as assessed by the treating investigator.
⁃ Complete all required baseline laboratory tests and imaging examinations within 28 days before randomization.
⁃ Normal organ and bone marrow function measured within 28 days prior to administration of study treatment.
⁃ Male and female subjects of reproductive/childbearing potential must have a documented negative pregnancy test within 2 weeks prior to randomization and agree to acceptable birth control (non-hormonal) during and up to 6 months after trial therapy.
∙ Subjects must satisfy all of the following additional criteria to be included in the OGT group:
• No absolute contraindication for invasive procedures to obtain samples for organoid generation.
• Sufficient material for organoid generation: biopsied samples (length\>1cm, 2-3 pieces), surgically resected samples (\>1cm×1cm×0.5cm, weight\>200mg), malignant effusion samples collected by thoracentesis, abdominocentesis or lumbar puncture (pleural fluid\>50mL, ascites\>50mL, cerebrospinal fluid≥4 tubes with each tube ≥4mL).
• Successful acquisition of a solid tumor biopsy sample containing ≥ 20% tumor content, or malignant effusion sample (e.g., pleural, or pericardial effusion or ascites) confirmed to contain malignant cells.