NCT04733118

Chemotherapy-Free pCR-Guided Strategy With Trastuzumab-pertuzumab and T-DM1 in HER2-positive Early Breast Cancer

Chemotherapy-Free pCR-Guided Strategy With Subcutaneous Trastuzumab-pertuzumab and T-DM1 in HER2-positive Early Breast Cancer (PHERGAIN-2)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 393 (actual)
• Sponsor: MedSIR · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multicenter, open-label, single-arm, one-stage, phase II study to assess the efficacy of a chemotherapy-free pathological complete response (pCR)-guided strategy with trastuzumab and pertuzumab (given as a subcutaneous fixed-dose combination) and T-DM1, for patients with previously untreated HER2-positive early breast cancer.

Detailed description

Patients ≥ 18 years of age with previously untreated HER2 IHC 3+ invasive carcinoma according to ASCO/CAP 2018 guidelines. Tumor size between \>5 to 30 mm by breast MRI and node-negative status by clinical exam, MRI, and ultrasound. In patients with suspected axillary node involvement, a negative fine needle aspiration biopsy (FNAB) will be mandatory. Central review for: Breast MRI. HER2 status. Neoadjuvant treatment will consist In 8 cycles of fixed-dose subcutaneous (SC FDC) HP combination (± ET according to HR status). urgery will be performed within 4 weeks from the last cycle of HP (sentinel node biopsy will be mandatory; subsequent axillary dissection will be performed according to local guidelines). Surgery will require free margins for any infiltrating or DCIS lesion. Radiotherapy will be mandatory for patients with breast preservation. Adjuvant systemic therapy will be started within 4 weeks from surgery depending on pathological report: Arm A: pCR (breast and axilla): HP SC FDC x 10 cycles. Arm B: Residual invasive breast tumor and/or ypN0(i+), ypN0(mol+), ypN1mi: T-DM1 x 10 cycles Arm C: ypN1 to N3: T-DM1 x 10 cycles, with physician's choice chemotherapy allowed between surgery and T-DM1. All patients with HR\[+\] tumors will receive adjuvant ET up to at least 5 years (ET will also be administered in association with adjuvant HP or T-DM1, with the exception of the cycles involving the use of chemotherapy in Arm C).

Conditions

• Early Breast Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab and Pertuzumab (FDC SC) and T-DM1	Patients will receive Trastuzumab and Pertuzumab as a subcutaneous fixed-dose combination (PH FDC SC) (± ET depending on HR status) for 8 3-week cycles, on day 1 only. ET will consist of letrozole for post-menopausal women or tamoxifen ± ovarian function suppression (OFS) for pre-menopausal women administered continuously. Men will receive tamoxifen. After completing neoadjuvant therapy, a final breast MRI will be performed 2 weeks prior to surgery. Surgery will be performed within 4 weeks after completion of the last cycle of PH FDC SC. Adjuvant systemic therapy will start within 4 weeks from surgery. There will be three different cohorts depending on pathological report: * Cohort A: PH FDC SC ± ET for 10 additional 3-week cycles * Cohort B: T-DM1 ± ET for 10 cycles * Cohort C: T-DM1 ± ET for 10 cycles, with possibility of physician's choice chemotherapy before adjuvant T-DM1.

Timeline

• Start date: 2021-08-05
• Primary completion: 2027-03-01
• Completion: 2028-03-01
• First posted: 2021-02-01
• Last updated: 2025-11-20

Locations

41 sites across 5 countries: Bulgaria, Germany, Hungary, Italy, Spain