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

NCT ID: NCT05388149

Last Updated: 2025-01-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-06
• Study Completion Date: 2026-07-31

Brief Summary

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.

Conditions

Breast Cancer; HER2-positive Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neratinib Arm

Standard T-DM1 (3.6mg/kg) IV infusion every 3 weeks administered with Neratinib (160 mg) orally once daily up to 1 year.

Group Type: EXPERIMENTAL

Neratinib

Intervention Type: DRUG

Neratinib administered as 40mg tablets

Interventions

Neratinib

Neratinib administered as 40mg tablets

Intervention Type: DRUG

Other Intervention Names

NERLYNX

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Receiving adjuvant T-DM1, with evidence of MRD (positive test by Inivata RaDaR) after receiving 2-6 cycles of T-DM1

3. No contraindications to T-DM1 or neratinib

4. No clinical or radiographic evidence of recurrent or metastatic disease

5. 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

6. ECOG performance status 0-1.

7. Patient must have adequate organ function

8. WOCBP must have a negative serum [beta] HCG test result.

9. WOCBP must agree to use highly effective contraception

10. Male participants must agree to use highly effective contraception

11. 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.

12. Signed informed consent

Exclusion Criteria

1. Prior therapy with any HER2 tyrosine kinase inhibitor

2. Clinical or radiographic evidence of suspected or confirmed metastatic disease.

3. Previous or concurrent malignancy within 3 years of study entry, with exceptions

4. Impaired cardiovascular function or clinically significant cardiovascular diseases

5. Known positive serology for HIV that is not currently controlled with anti-retroviral therapy,

6. 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.

7. Impaired gastrointestinal function or disease that may significantly alter the absorption of neratinib

8. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Health Network: Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

David Cescon, MD PhD

Role: CONTACT

Dave.cescon@uhn.ca

416-946-2245

Facility Contacts

Dave Cescon, M.D.

Role: primary

dave.cescon@uhn.ca

416-946-2245

Other Identifiers

KAN-HER2 MRD

Identifier Type: OTHER

Identifier Source: secondary_id

22-5307

Identifier Type: -

Identifier Source: org_study_id