A Phase 2 Neoadjuvant Study of Zanidatamab in Combination With Chemotherapy in Participants With HER2-positive Breast Cancer

Official title

A Phase 2, Randomized, Multicenter, Open-label Neoadjuvant Study Evaluating Zanidatamab in Combination With Chemotherapy in Participants With HER2-positive Breast Cancer

Overview

The purpose of this study is to see if zanidatamab is safe and effective, when combined with chemotherapy, in treating people who has Human Epidermal Growth Factor Receptor 2 (HER2)-positive, early-stage breast cancer

Interventions

• Drug Zanidatamab
  Administered intravenously (IV)
• Drug Paclitaxel
  Administered intravenously (IV)
• Drug Docetaxel
  Administered intravenously (IV)
• Drug Carboplatin
  Administered intravenously (IV)
• Drug Trastuzumab
  Administered intravenously (IV)
• Drug Pertuzumab
  Administered intravenously (IV)

Primary outcome measures

• Number of participants with pCR [Time frame: Up to 8 months]

Secondary outcome measures (11)

• Number of participants with Pathologic response by Residual Cancer Burden (RCB) classification [Time frame: Up to 8 months]
• Number of Participants with Treatment-emergent Adverse Events (TEAEs) [Time frame: Up to 23 months]
• Number of Participants Discontinuing Study Treatment Due to TEAEs [Time frame: Up to 23 months]
• Number of participants that completed breast conservation surgery (BCS) [Time frame: Up to 8 months]
• Event Free Survival (EFS) [Time frame: Up to 46 months]
• Overall Survival (OS) [Time frame: Up to 46 months]
• Number of participants reporting Symptomatic Adverse Events based on Patient-reported Outcome-Common Terminology Criteria for AEs (PRO-CTCAE) [Time frame: Up to 23 months]
• Number of participants reporting Symptomatic Adverse Events based on European Organisation for Research and Treatment of Cancer (EORTC) Item Library [Time frame: Up to 23 months]
• Percentage of all treated participants reporting overall side-effect bother on the Functional Assessment of Chronic Illness Therapy General Physical Item 5 (FACIT-GP5) [Time frame: Up to 23 months]
• Serum Concentrations of Zanidatamab [Time frame: Up to 18 months]
• Number of Participants Positive for Anti-drug Antibodies to Zanidatamab [Time frame: Up to 18 months]

Eligibility criteria

Inclusion criteria

• Has newly diagnosed Stage II or III histologically confirmed invasive breast carcinoma.
• Has histologically confirmed HER2-positive breast cancer
• Has a known hormone receptor (HR) status of the primary tumor
• Participants with multifocal or multicentric disease are eligible if the largest tumor (which must be larger than or equal to 2 cm in diameter) is HER2-positive, and the treating physician has determined the participant should be treated as HER2-positive.
• Agrees to undergo a mastectomy or breast conserving surgery (BCS) after neoadjuvant therapy.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function
• Has an LVEF ≥ 50% as determined by either ECHO or MUGA obtained within 6 weeks prior to randomization.
• Adequate contraceptive precautions
• Participants with known HIV are eligible unless:

• CD4+ T Cell count is less than or equal to 350 microliters (uL)
• Detectable viral load, or
• Receiving protease inhibitors or cobicistat

Exclusion criteria

• Has Stage IV (metastatic) breast cancer.
• Has bilateral breast cancer.
• Has a history of any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the investigator, could affect the participant's involvement in the study.
• Has uncontrolled hypertension
• Has significant symptoms from peripheral neuropathy
• Has an active uncontrolled infection
• Has a history of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of zanidatamab or other study interventions.
• Known active hepatitis B or C infection.
• Has another malignancy diagnosed within the last 5 years. Exceptions include previously treated non melanomatous skin cancers, carcinoma in-situ, and melanoma in-situ. Participants with prior ipsilateral ductal carcinoma in situ (DCIS) or invasive breast cancer are not eligible.
• Was treated with surgery, chemotherapy, anti-HER2 therapy, radiation therapy, endocrine therapy, or experimental therapy for invasive breast cancer
• Is planning to receive concurrent therapy with any other investigational agent or anti-cancer therapy not specified in the protocol
• Receipt of a live vaccine within 4 weeks prior to enrollment
• Has a known hypersensitivity to any components of the study interventions, including chemotherapy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 27 centers

• Oncology Institute — Long Beach
• Cancer & Blood Research Center — Los Alamitos
• Rocky Mountain Cancer Centers — Denver
• Holy Cross Hospital — Fort Lauderdale
• The Oncology Institute — Lakeland
• Accellacare of McFarland — Ames
• LSU Health Sciences Center — Shreveport
• New England Cancer Specialists — Scarborough
• … and 19 more centers

Spain · 5 centers

• Hospital Clínico San Cecilio — Granada
• Álvaro Cunqueiro Hospital — Vigo
• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital Universitario Clinico San Cecilio, — Granada
• Hosp Beata María Ana de Jesús — Madrid

Italy · 1 center

• Ospedale San Raffaele — Milan

Identifiers

NCT: NCT07102381 · JZP598-208 · 2025-523204-68-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗