Kadcyla And Neratinib for Interception of HER2+ Breast Cancer With Molecular Residual Disease
This is a Phase 2 study for patients with resected Stage I-III HER2+ breast cancer with detected molecular residual disease (MRD+) following standard neoadjuvant and locoregional therapy delivered with curative intent. In this study Patients will be treated with neratinib in addition to their standard T-DM1 adjuvant therapy. Neratinib will be administered orally at a dose of 160 mg daily for up to 12 months, or until the time of clinical recurrence, discontinuation due to toxicity, or withdrawal of consent. This study will have two stages, stage 1 would enroll up to 8 participants to clear the Minimal Residual Disease (MRD) and Stage 2 will enroll up to 5 participants. The purpose of this study is to determine if this study population would have a better outcome from adding neratinib to their standard T-DM1 adjuvant therapy.
• Male or female patients ≥ 18 years of age with histologically confirmed, resected HER2 positive stage I-III breast cancer, with residual invasive disease following prior neoadjuvant trastuzumab (+/- pertuzumab)-based chemotherapy.
• Receiving adjuvant T-DM1, with evidence of MRD (positive test by Inivata RaDaR) after receiving 2-6 cycles of T-DM1
• No contraindications to T-DM1 or neratinib
• No clinical or radiographic evidence of recurrent or metastatic disease
• Previous Therapy requirements:
‣ Received 2-6 cycles of trastuzumab-DM1 in the adjuvant setting
⁃ Received min of 12 weeks of endocrine therapy (ER+ patients)
⁃ Adjuvant radiation permitted (minimum 14-day washout required)
⁃ No prior neratinib or other HER2 tyrosine kinase inhibitor
• ECOG performance status 0-1.
• Patient must have adequate organ function
• WOCBP must have a negative serum \[beta\] HCG test result.
• WOCBP must agree to use highly effective contraception
⁃ Male participants must agree to use highly effective contraception
⁃ Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
⁃ Signed informed consent