HER2-positive metastatic breast cancer
Conditions
Interventions
Phase 1 Adaptive Design:Cohort A: Neratinib + Vinorelbine + Anlotinib (dose-escalation cohort)
Cohort B: Neratinib + Oral Vinorelbine Capsules + Inetetamab
Phase 2 Adaptive Design:Cohort A: Neratinib + Vinorelbine + Anlotinib
Cohort B: Neratinib + Oral Vinorelbine Capsules + Inetetamab
Sponsors
Shanghai GoBroad Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Aged between 18 and 75 years old. 2.Pathologically confirmed HER2-positive metastatic breast cancer; HER2 status of primary and/or metastatic lesions is IHC 3+, and/or FISH-positive. If multiple results are available, the status from the most recent biopsy shall be adopted. 3.Only for Cohort A1: a) Patients who have received prior TKI therapy in neoadjuvant/adjuvant setting and are TKI-sensitive (i.e., disease relapse >= 1 year after the last TKI treatment), or have received TKI therapy in recurrent/metastatic setting. b) Patients who are ineligible for T-DXd treatment and have not received T-DXd previously. 4.Only for Cohort A2: a) Patients with prior T-DXd treatment for breast cancer. b) No prior exposure to any TKI. 5.Only for Cohort A3: a) Patients previously treated with trastuzumab combined with taxane chemotherapy for metastatic breast cancer. b) No prior TKI or T-DXd exposure in any prior lines of therapy. 6.Only for Cohort B: a) No prior TKI treatment; or received TKI in neoadjuvant/adjuvant setting with TKI sensitivity (i.e., disease relapse >= 1 year after the last TKI administration). b) Prior treatment with trastuzumab plus pertuzumab (HP) combination. 7.CNS eligibility for Cohort A: Based on screening contrast-enhanced brain MRI, patients must meet one of the following: a) No evidence of brain metastasis. b) Untreated brain metastases with lesion diameter = 21 days Stereotactic radiosurgery (SRS): >= 7 days Surgical resection: >= 28 days iii) Complete medical records of all prior CNS treatments must be provided for classification of target and non-target lesions. 8.CNS eligibility for Cohort B: Based on screening contrast-enhanced brain MRI, patients must meet one of the following: a) Untreated brain metastases with lesion diameter = 21 days Stereotactic radiosurgery (SRS): >= 7 days Surgical resection: >= 28 days iii) Complete medical records of all prior CNS treatments must be provided for classification of target and non-target lesions. 9.At least one measurable lesion as defined by RECIST 1.1. 10.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 11.Expected survival >= 12 weeks. 12.All clinically significant adverse reactions related to prior anti-tumor therapy have recovered (alopecia excluded). 13.Left ventricular ejection fraction (LVEF) within the normal range as per local institutional criteria. 14.Screening laboratory paramete
Exclusion criteria
Exclusion criteria: 1. Patients who have received major surgery, chemotherapy, curative radiotherapy, investigational drug therapy or other anti-tumor therapy within 2 weeks prior to the first study drug administration. No washout period is required for palliative radiotherapy. 2. CNS exclusion criteria: Based on screening brain MRI, patients with any of the following conditions should be excluded: a) Requiring systemic corticosteroids (e.g., dexamethasone > 2 mg or equivalent) to control symptoms of brain metastases. b) Known or suspected leptomeningeal disease (LMD) documented by the investigator. c) Uncontrolled generalized or complex partial seizures (more than 1 episode per week), or progressive neurological symptoms caused by brain metastases despite targeted CNS treatment. (Antiepileptic medications are permitted to be continued during the study.); 3. Only for Cohort A: a) Prior use of anti-angiogenic agents such as bevacizumab. b) Or patients with bleeding tendency, thrombosis, or uncontrolled hypertension. 4. QTc interval > 0.47 s, or known history of QTc prolongation or torsades de pointes. 5. Presence of clinically significant or uncontrolled cardiac diseases, including congestive heart failure (NYHA functional class >= 2), angina requiring treatment, myocardial infarction within the past 12 months, or any clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention. 6. Pregnant or breastfeeding women. 7. Patients with chronic gastrointestinal diseases or recent history of acute gastrointestinal disease manifested mainly as diarrhea (e.g., Crohn’s disease, malabsorption, or Grade >= 2 diarrhea of any etiology at baseline). 8. Presence of Grade >= 2 motor or sensory neuropathy. 9. Known HIV seropositivity; and/or HBsAg positive with HBV DNA above the lower limit of detection without standardized antiviral treatment; and/or positive anti-HCV antibody. 10. Known hypersensitivity to vinorelbine, neratinib, or any of their excipients; in Cohort A, known hypersensitivity to anlotinib or any of its excipients is excluded; in Cohort B, patients with hypersensitivity to anti-HER2 monoclonal antibodies are also excluded. 11. History of any second primary malignancy within 3 years prior to screening, except contralateral breast cancer, adequately treated carcinoma in situ of the cervix, or adequately treated basal cell or squamous cell carcinoma of the skin. 12. Clinically significant infection requiring systemic treatment within 2 weeks prior to the first study drug administration. 13. Patients with any other clinically significant medical condition or abnormal laboratory findings that, in the investigator’s judgment, make the patient unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate;Scale score;Physical examination findings;Disease Control Rate;Laboratory test results;Adverse Event;1-year overall survival rate; | — |
Countries
China
Contacts
Public ContactLi Jin
Shanghai East Hospital
Outcome results
None listed