Classifying for HER2 Dependence to De-Escalate Neoadjuvant Chemotherapy in Patients With HER2+ Early Breast Cancer Undergoing HER2 Double-Blockade

NCT06068985 | Active Not Recruiting Phase 2

• 2 other identifiers: LACOG 0721ML44079
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 14

Brief Summary

This study aims to identify HER2-positive early-stage breast cancer patients who could benefit from neoadjuvant treatment using PHESGO™ (pertuzumab and trastuzumab) without chemotherapy. The approach involves utilizing specific biomarkers (HR and HER2 IHC status) to select participants whose tumors strongly rely on the HER2 pathway, potentially benefiting from a HER2-targeted approach without chemotherapy concurrently.

Conditions

HER2-positive Breast Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR) Rate

  This outcome measures the rate of participants with HER2-positive early breast cancer who achieve a pathologic complete response (pCR) following neoadjuvant treatment with PHESGO™ without concurrent chemotherapy. Participants selected based on high HER2 pathway dependence and demonstrating a favorable PET-CT response after the third therapy cycle are evaluated for the absence of residual invasive tumor cells in the breast and lymph nodes.

  After eight neoadjuvant cycles of PHESGO™ (each cycle is 21 days)

Secondary Outcomes (9)

• Rate of Favorable PET-CT Response

  After three neoadjuvant PHESGO™ cycles (each cycle is 21 days)

• Pathologic Response via Residual Cancer Burden (RCB)

  Immediately after the end of treatment

• Objective Response Rate by PERCIST 1.0

  After three neoadjuvant PHESGO™ cycles (each cycle is 21 days)

• Objective Response Rate by RECIST 1.1

  After eight neoadjuvant cycles of PHESGO™ (each cycle is 21 days)

• Invasive Disease-Free Survival (iDFS) Stratified by pCR

  From enrollment until an event related to invasive disease occurs, stratified by pCR, assessed up to 5 years

Study Arms (1)

PHESGO™-Based Neoadjuvant Therapy for HER2-Positive Early Breast Cancer

EXPERIMENTAL

This is a single-arm phase II neoadjuvant study using PHESGO™. Participants will receive three cycles of neoadjuvant PHESGO™, with a specific dosage regimen. After three cycles, participants will be reevaluated based on their PET-CT response. PET-CT response is defined as a ≥40% reduction in SUVMax without metabolic progression in non-target lesions. Responders will receive 5 additional cycles of PHESGO™ before surgery. Non-responders will exit the study, following institutional guidelines. Local surgery follows 8 cycles. Adjuvant therapy varies based on pCR status: 1 year of PHESGO™ for pCR; T-DM1 for 14 cycles or investigator's choice chemotherapy plus 10 additional adjuvant cycles of PHESGO™ for non-pCR cases.

Drug: PHESGO

Interventions

PHESGO DRUG

Subcutaneous formulation with pertuzumab and trastuzumab.

PHESGO™-Based Neoadjuvant Therapy for HER2-Positive Early Breast Cancer

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed ICF; Women between 18-80 years of age at time of signing ICF.
• ECOG ≤ 1
• HER2+ breast cancer with clinical stage at presentation: T1cN1, T2, N0-1
• HER2 3+ by IHC, with strongly positive staining for HER2 protein in ≥ 80% of cells, and absence of HER2 negative areas in the tumor
• ER IHC ≤10%
• PR IHC negative (\<1%) or 0% of tumor cell nuclei
• Tumors must have at least 10mm measured by breast echography and be assessable for SUVMax (maximum standardized uptake value (SUVmax) ≥ 2.5) using 18FDG-PET-CT scan on baseline imaging.
• Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue block for central confirmation of HER2 and hormone receptor status and additional biomarker research.
• Baseline LVEF ≥ 55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA).
• For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent (refrain from heterosexual intercourse) or use one highly effective non-hormonal contraceptive method with a failure rate of \< 1% per year, or two effective non-hormonal contraceptive methods during the treatment period and for 7 months after the last dose of HER2-targeted therapy, and agreement to refrain from donating eggs during this same period.
• A negative serum pregnancy test must be available prior to randomization for WOCBP (premenopausal women and women \< 12 months after the onset of menopause), unless they have undergone surgical sterilization (removal of ovaries and/or uterus)

You may not qualify if:

• Patients with metastatic disease.
• Any previous systemic chemotherapy or anti-HER2 targeted therapy directed to breast cancer.
• Patients with clinical N2 or N3 disease, T4, or inflammatory breast cancer.
• Concurrent serious diseases that may interfere with planned treatment.
• Patients with a history of concurrent or previously treated non-breast malignancies except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin. A patient with previous invasive non-breast cancer is eligible provided he/she has been disease free for more than 5 years.
• Patients who have received any previous systemic therapy (including chemotherapy, immunotherapy, HER2-targeted agents, endocrine therapy (selective estrogen receptor modulators, aromatase inhibitors, and antitumor vaccines) for treatment or prevention of breast cancer.
• Patients who have a history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) if they have received any systemic therapy for its treatment, or radiation therapy to the ipsilateral breast. Patients are allowed to enter the study if treated with surgery alone.
• Patients with high-risk for breast cancer who have received chemopreventive drugs in the past are not allowed to enter the study.
• Patients with bilateral breast cancer.
• Patients who have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes.
• Axillary lymph node dissection (ALND) or Sentinel lymph node biopsy (SLNB) prior to initiation of neoadjuvant therapy. Patients with clinically negative axilla (by physical examination and radiographic imaging) may undergo a core or needle biopsy procedure prior to neoadjuvant systemic therapy.
• Treatment with any investigational drug within 28 days prior to randomization.
• Serious cardiac illness or medical conditions.
• Inadequate bone marrow function.
• Impaired liver function.

Sponsors & Collaborators

• Oncoclínicas: collaborator
• Latin American Cooperative Oncology Group: lead
• Roche Pharma AG: collaborator

Study Sites (14)

Núcleo de Oncologia da Bahia - NOB (Oncoclínicas)

Salvador, Estado de Bahia, 40.170-110, Brazil

Location

Centro de Câncer de Brasília - CETTRO (Oncoclínicas)

Brasília, Federal District, 70.710-904, Brazil

Location

Oncocentro Belo Horizonte (Oncoclínicas)

Belo Horizonte, Minas Gerais, 30.360-680, Brazil

Location

Centro de Pesquisa Vencer & Oncoclínica

Teresina, Piauí, 60.449-200, Brazil

Location

Instituto Nacional de Câncer - INCA

Rio de Janeiro, Rio de Janeiro, 20.230-130, Brazil

Location

Hospital da Fundação Oswaldo Aranha - HFOA

Volta Redonda, Rio de Janeiro, 27.251-260, Brazil

Location

Santa Casa de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90.050-170, Brazil

Location

Centro de Pesquisa em Oncologia do Hospital São Lucas da PUCRS - CPO

Porto Alegre, Rio Grande do Sul, 90.610-000, Brazil

Location

Universidade Estadual de Campinas - UNICAMP

Campinas, São Paulo, 13.083-881, Brazil

Location

Instituto do Câncer do Estado de São Paulo - ICESP

São Paulo, São Paulo, 01.246-000, Brazil

Location

Centro de Pesquisa do Hospital Pérola Byington

São Paulo, São Paulo, 01.317-000, Brazil

Location

A.C. Camargo Cancer Center

São Paulo, São Paulo, 01.509-001, Brazil

Location

Centro Paulista de Oncologia (Oncoclínicas)

São Paulo, São Paulo, 04.538-135, Brazil

Location

Hospital de Amor de Barretos

São Paulo, São Paulo, 14.784-400, Brazil

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Sérgio Simon

  Oncoclínicas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: October 5, 2023
• Study Start: September 5, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2032
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

BR (14)