Kadcyla And Neratinib for Interception of HER2+ Breast Cancer With Molecular Residual Disease

Inclusion criteria

• 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

Exclusion criteria

• Prior therapy with any HER2 tyrosine kinase inhibitor
• Clinical or radiographic evidence of suspected or confirmed metastatic disease.
• Previous or concurrent malignancy within 3 years of study entry, with exceptions
• Impaired cardiovascular function or clinically significant cardiovascular diseases
• Known positive serology for HIV that is not currently controlled with anti-retroviral therapy,
• Has a known history of or is positive for active hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (defined as HCV RNA [qualitative] is detected). HBV DNA must be undetectable and HBsAg negative at Screening Visit. Participants who have had definitive treatment for HCV are permitted if HCV RNA is undetectable at Screening Visit.
• Impaired gastrointestinal function or disease that may significantly alter the absorption of neratinib
• Medical, psychiatric, cognitive, or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol, or complete the study.