Durvalumab With Trastuzumab and Pertuzumab in HER2-Enriched Breast Cancer

NCT03820141 | Active Not Recruiting Phase 2 Results FDA Drug

• 1 other identifier: Pro00020917
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to test the safety and effectiveness of using durvalumab with trastuzumab and pertuzumab in participants with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological Response Rate (RCB-0 and RCB-1) Rate in the Breast in Patients With HER2-enriched and HER2-amplified Breast Cancer

  Determination of the pathologic response rate \[residual cancer burden (RCB)- 0, and RCB 1\] in the breast of durvalumab with trastuzumab and pertuzumab combination in patients with HER2-enriched and HER2-amplified breast cancer.

  18 weeks

Secondary Outcomes (4)

• pCR Rate in the Breast in Patients Whose Tumors Have <5% and ≥5% TILs

  18 weeks

• pCR Rate in Patients With (PD-L1)-Positive and PD-L1-Negative Tumors

  18 weeks

• Three-year Disease-free Survival (DFS) Rate in Patients Who Achieve pCR

  3 years

• Number of Participants With Treatment-related Adverse Events

  18 weeks

Study Arms (1)

Durvalumab + Trastuzumab + Pertuzumab

EXPERIMENTAL

Durvalumab, trastuzumab, and pertuzumab will be administered on Day 1 every 3 weeks for 6 cycles. Trastuzumab will be administered as 8 mg/kg intravenous (IV) loading dose, followed by 6 mg/kg IV. Pertuzumab will be administered as 840 mg IV loading dose, followed by 420 mg. Durvalumab will be administered at a fixed dose of 1120 mg IV.

Drug: Durvalumab; Drug: Trastuzumab; Drug: Pertuzumab

Interventions

Durvalumab DRUG

programmed cell death-ligand 1 inhibitor

Also known as: IMFINZI, MEDI4736

Durvalumab + Trastuzumab + Pertuzumab

Trastuzumab DRUG

anti-HER2 monoclonal antibody

Also known as: Herceptin

Durvalumab + Trastuzumab + Pertuzumab

Pertuzumab DRUG

anti-HER2 monoclonal antibody

Also known as: Perjeta

Durvalumab + Trastuzumab + Pertuzumab

Eligibility Criteria

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

You may qualify if:

• Female aged \>18 years at the time of study entry.
• Histologically confirmed HER2-enriched (by BluePrint) and HER2-amplified (ERBB2 mRNA \>7.5-10) breast cancer.
• Estrogen receptor and progesterone receptor negative.
• Primary tumor greater than 1 cm diameter, measured by clinical examination and mammography or echography.
• Any nodal status
• Bilateral breast cancers that individually meet eligibility criteria are allowed.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Adequate organ and marrow function.
• Baseline left ventricular ejection fraction greater than or equal to 50%, as measured by multigated acquisition scan or echocardiogram.
• Evidence of postmenopausal status or negative serum pregnancy test for premenopausal patients. Negative serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to the first dose of study treatment for premenopausal patients.
• Willing to provide biopsy tissues as required by the study.
• 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.

You may not qualify if:

• Participation in another clinical study with an investigational product within 28 days prior to the first dose of study treatment.
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Unresolved or unstable adverse events from prior administration of another investigational drug.
• Any concurrent chemotherapy, radiation therapy, immunotherapy, or biologic therapy for cancer treatment.
• Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study treatment.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders.
• History of active primary immunodeficiency.
• Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment.
• Patients who are pregnant or breastfeeding or patients of reproductive potential who are not willing to employ effective birth control from screening to 7 months after the last dose of study treatment.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Patients with a mean QT interval of greater than or equal to 470ms calculated from 3 EKGs
• Patients with underlying cardiovascular conditions that have recently undergone interventions including: cardiac ventricular arrhythmia requiring medication, history of second or third degree AV blocks, myocardial infarction with the previous year, congestive heart failure, and unstable angina

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead
• AstraZeneca: collaborator

Study Sites (1)

Houston Methodist Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

durvalumab; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Polly Niravath, M.D.
• Organization: Houston Methodist Neal Cancer Center

paniravath@houstonmethodist.org

7134418324

Study Officials

• Polly Niravath, M.D.

  Houston Methodist Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oncologist, Houston Methodist Neal Cancer Center

Study Record Dates

• First Submitted: January 25, 2019
• First Posted: January 29, 2019
• Study Start: June 30, 2020
• Primary Completion: October 30, 2024
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 20, 2026
• Results First Posted: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)