Clinical trial • Phase II • Oncology

ZANIDATAMAB for HER2-positive breast cancer

Phase II trial of ZANIDATAMAB for HER2-positive breast cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
HER2-positive breast cancer
Trial Stage
Phase II
Drug Modality
Bispecific antibody | Monoclonal antibody | ADC | Small molecule

Key dates

Initial CTIS Submission Date
05-09-2025
First CTIS Authorization Date
22-12-2025

Trial design

Randomised, open-label, arm c: trastuzumab + pertuzumab + docetaxel + carboplatin (no dosing schedule specified in the record)-controlled Phase II trial in Italy, Spain, Germany.

Randomised
Yes
Open Label
Yes
Comparator
Arm C: trastuzumab + pertuzumab + docetaxel + carboplatin (no dosing schedule specified in the record)
Target Sample Size
65

Eligibility

Recruits 65 Vulnerable population selected. Participants must be adults (Is at least 18 years of age or of the legal adult age per local standard) and 'Is capable of giving signed informed consent as described in Section 10.1.3.' Consent requirements referenced in Section 10.1.3; no paediatric assent procedures (study restricted to adults)..

Pregnancy Exclusion
Female participants who are breastfeeding or pregnant and female and male participants planning a pregnancy.
Vulnerable Population
Vulnerable population selected. Participants must be adults (Is at least 18 years of age or of the legal adult age per local standard) and 'Is capable of giving signed informed consent as described in Section 10.1.3.' Consent requirements referenced in Section 10.1.3; no paediatric assent procedures (study restricted to adults).

Inclusion criteria

  • {"criterion_text":"- Is at least 18 years of age or of the legal adult age per local standard at the time of signing the informed consent.\n- Participant agrees to the following based on sex assigned at birth.\n- Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 months after the last dose of all study interventions or the contraception period for the chemotherapy per local guidance/standard practice, whichever is longer.\n- A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: o Is a WONCBP as defined in Appendix 5 Contraceptive and Barrier Guidance. OR − Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), with low user dependency or a highly effective method that is user dependent OR 2 effective nonhormonal contraceptive methods that are user dependent, as described in Table 16 of Appendix 5 Contraceptive and Barrier Guidance, during the study intervention period and for at least 7 months after the last dose of all study interventions. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention. This requirement aligns with the contraception period recommended for trastuzumab and is longer than the recommended contraception period for zanidatamab, which is 4 months, and for all other allowed chemotherapy options. Therefore, 7 months is considered sufficient to collect details of all pregnancies.\n- Is capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.\n- Has Stage II or III (according to AJCC cancer staging manual anatomic staging table, edition 8) histologically confirmed invasive breast carcinoma. A minimum tumor size of 2 cm determined by imaging is required (for participants whose tumors are node negative or node positive). Participants with inflammatory breast cancer (T4d) are eligible.\n- Has histologically confirmed HER2-positive breast cancer according to ASCO/CAP Guidelines\n- Has a known HR status of the primary tumor performed by local immunohistochemical methods according to the institution standard protocol. Participants may have HR-positive or HR-negative disease, as defined by ASCO-CAP guidelines.\n- 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.\n- Agrees to undergo a mastectomy or BCS after neoadjuvant therapy.\n- Has an ECOG performance status of 0 or 1.\n- The participant meets the baseline laboratory criteria\n- The participant has LVEF ≥ 50% as determined by either ECHO or MUGA obtained within 4 weeks prior to first dose of study intervention."}

Exclusion criteria

  • {"criterion_text":"- Has Stage IV (metastatic) breast cancer.\n- Was treated with chemotherapy, anti-HER2 therapy, radiation therapy, endocrine therapy, or experimental therapy for invasive breast cancer (or DCIS if ipsilateral as the invasive breast cancer).\n- Is planning to receive concurrent therapy with any other investigational agent or anticancer therapy not specified in the protocol prior to the EOT Visit, including chemotherapy; radiotherapy (except for adjuvant radiotherapy for breast cancer after completion of chemotherapy); immunotherapy; or biological, hormonal or targeted anticancer therapy. Estrogen replacement therapy is not permitted in participants with HR-positive tumors.\n- Receipt of a live vaccine within 4 weeks prior to enrollment.\n- Female participants who are breastfeeding or pregnant and female and male participants planning a pregnancy.\n- Has a known hypersensitivity to any components of the study interventions, including chemotherapy.\n- Has bilateral breast cancer.\n- Has a history (≤ 6 months before the start of treatment) 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.\n- Has uncontrolled hypertension (systolic > 180 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (ie, active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to the first dose of study intervention, ventricular arrhythmia requiring therapy, or congestive heart failure of New York Heart Association (NYHA) Class II or higher.\n- Has significant symptoms (Grade ≥ 2) from peripheral neuropathy.\n- Has an active uncontrolled (febrile within the last 48 hours; no evidence of hypotension; no ongoing systemic sequela) infection (≥ Grade 2).\n- 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.\n- Known active hepatitis B or C infection.\n- Has another malignancy diagnosed within the last 5 years. Exceptions include previously treated nonmelanomatous skin cancers, carcinoma in-situ, and melanoma in-situ."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Local evaluation of pCR rate in the breast and axilla (defined as ypT0/Tis ypN0 per AJCC), as determined by local site pathologist blinded to treatment assignment","definition_or_measurement_approach":"Defined as ypT0/Tis ypN0 per AJCC; determined by local site pathologist blinded to treatment assignment (local evaluation)."}

Secondary endpoints

  • {"endpoint_text":"- Pathologic response by RCB classification and score (per NeoSTEEP criteria)","definition_or_measurement_approach":"Per NeoSTEEP criteria; distribution of RCB classification and scores at time of surgery in each treatment arm."}
  • {"endpoint_text":"- Incidence, nature, and severity of TEAEs","definition_or_measurement_approach":"Standard safety assessment of treatment-emergent adverse events (TEAEs); nature and severity recorded (no additional measurement detail in record)."}
  • {"endpoint_text":"- Frequency of discontinuations of treatment due to TEAEs","definition_or_measurement_approach":"Count of participants discontinuing treatment due to TEAEs (as recorded in safety data)."}
  • {"endpoint_text":"- Ovarian function in premenopausal women with ovaries as assessed by clinical measures and laboratory biomarkers","definition_or_measurement_approach":"Assessment by clinical measures and laboratory biomarkers (specific biomarkers not detailed in record)."}
  • {"endpoint_text":"- Rate of participants who receive surgery as intended","definition_or_measurement_approach":"Proportion of participants who receive the planned surgical intervention."}
  • {"endpoint_text":"- Rate of BCS in participants without inflammatory breast cancer","definition_or_measurement_approach":"Proportion of participants undergoing breast-conserving surgery (BCS) among those without inflammatory breast cancer."}
  • {"endpoint_text":"- EFS, defined as time from randomization to disease progression, disease recurrence (local, regional, distant, or contralateral [invasive]), or death from any cause","definition_or_measurement_approach":"Event-free survival measured as time (from randomization) to progression, recurrence (local/regional/distant/contralateral invasive) or death from any cause."}
  • {"endpoint_text":"- Overall Survival, defined as time from randomization to death from any cause","definition_or_measurement_approach":"Overall survival measured as time from randomization to death from any cause."}
  • {"endpoint_text":"- The frequency and severity of symptomatic AEs as assessed by the PRO-CTCAE and EORTC Item Library prior to first dose of study intervention and during the on-treatment period","definition_or_measurement_approach":"Patient-reported symptomatic adverse events assessed using PRO-CTCAE and the EORTC Item Library prior to first dose and during treatment."}
  • {"endpoint_text":"- The percentage of all treated participants, as treated, reporting each level of side-effect bother while on treatment, based on the FACIT-GP5","definition_or_measurement_approach":"Percentage distribution of side-effect bother levels during treatment using FACIT-GP5 instrument."}
  • {"endpoint_text":"- Serum concentrations of zanidatamab","definition_or_measurement_approach":"Pharmacokinetic measurement of zanidatamab serum concentrations (timing and assays not detailed here)."}
  • {"endpoint_text":"- Frequency, duration, and time of onset of anti-zanidatamab antibodies and neutralizing antibodies, if applicable","definition_or_measurement_approach":"Immunogenicity assessments: frequency, duration and time of onset of anti-drug and neutralizing antibodies."}

Recruitment

Planned Sample Size
65
Recruitment Window Months
54
Consent Approach
Participants must be adults (≥18 or legal adult per local law) and 'Is capable of giving signed informed consent as described in Section 10.1.3.' Subject information and informed consent forms (L1_SIS-and-ICF-Main-Public) are available in multiple languages (documents present for English, Spanish, Italian, German). No paediatric assent (study restricted to adults).

Geography

Total Number Of Sites
37
Total Number Of Participants
100

Italy

Earliest CTIS Part Ii Submission Date
06-11-2025
Latest Decision Or Authorization Date
22-12-2025
Processing Time Days
46
Number Of Sites
11
Number Of Participants
25

Sites

Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
Medical Oncologist
Contact Person Name
Marina Cazzaniga
Contact Person Email
marina.cazzaniga@unimib.it
Site Name
Humanitas Istituto Clinico Catanese S.p.A.
Department Name
Oncologia
Contact Person Name
Maria Vita Sano'
Site Name
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
PRECISION MEDICINE - UNIVERSITY OF CAMPANIA
Contact Person Name
Giulia Martini
Contact Person Email
giulia.martini@unicampania.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Head of Breast Cancer Group
Contact Person Name
Giampaolo Bianchini
Contact Person Email
bianchini.giampaolo@hsr.it
Site Name
University Magna Graecia Of Catanzaro
Department Name
Translational Medical Oncology Unit
Contact Person Name
Pierfrancesco Tassone
Contact Person Email
tassone@unicz.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Medical Oncologist
Contact Person Name
Claudio Zamagni
Contact Person Email
claudio.zamagni@aosp.bo.it
Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative
Contact Person Name
Giuseppe Curigliano
Contact Person Email
giuseppe.curigliano@ieo.it
Site Name
Azienda USL IRCCS Di Reggio Emilia
Department Name
Oncologia Medica Provanciale
Contact Person Name
Elisa Gasparini
Contact Person Email
elisa.gasparini2@ausl.re.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
Clinica di Oncologia Medica
Contact Person Name
Lucia Del Mastro
Contact Person Email
lucia.delmastro@hsanmartino.it
Site Name
Istituto Oncologico Veneto
Department Name
Dipartimento di Scienze Chirurgiche
Contact Person Name
Valentina Guarneri
Contact Person Email
valentine.guarneri@unipd.it
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
Breast Oncology Division
Contact Person Name
Michelino De Laurentiis

Spain

Earliest CTIS Part Ii Submission Date
25-11-2025
Latest Decision Or Authorization Date
11-01-2026
Processing Time Days
47
Number Of Sites
14
Number Of Participants
35

Sites

Site Name
Hospital Beata Maria Ana
Department Name
Oncology
Contact Person Name
Maria Gion
Contact Person Email
mariagion@gmail.com
Site Name
Hospital Alvaro Cunqueiro
Department Name
Oncology Service
Contact Person Name
Isaura Fernandez Perez
Site Name
Hospital Universitari Vall D Hebron
Department Name
Medical Oncologist
Contact Person Name
Santiago Escriva de Romani
Contact Person Email
sescriva@vhio.net
Site Name
Hospital Clinico San Carlos
Department Name
Oncology
Contact Person Name
Jose Garcia-Saenz
Contact Person Email
jgsaenz@salud.madrid.org
Site Name
Hospital Universitario 12 De Octubre
Department Name
Medical Oncology
Contact Person Name
Eva Ciruelos
Contact Person Email
eva.ciruelos@gmail.com
Site Name
Hospital Universitario Donostia
Department Name
Oncology
Contact Person Name
Ander Urruticoechea
Site Name
University Hospital Son Espases
Department Name
Oncology
Contact Person Name
Antonia Perello Martorell
Contact Person Email
antonia.perellom@ssib.es
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Oncology
Contact Person Name
Juan Cejalvo
Contact Person Email
juanmitch5@hotmail.com
Site Name
Hospital Universitario Virgen De La Victoria
Department Name
Servicio de Oncologia Medica
Contact Person Name
Emilio Alba
Contact Person Email
emilioalbac@gmail.com
Site Name
Hospital Universitario Clinico San Cecilio
Department Name
Servicio de Oncología
Contact Person Name
Isabel Blancas
Site Name
Hospital Clinic De Barcelona
Department Name
Oncology
Contact Person Name
Maria Vidal
Contact Person Email
mjvidal@clinic.cat
Site Name
Institut Catala D'oncologia
Department Name
Oncology
Contact Person Name
Sonia Pernas
Site Name
Hospital Del Mar
Department Name
Oncology
Contact Person Name
Sonia Servitja
Contact Person Email
sservitja@hmar.cat
Site Name
Hospital Universitario Virgen De La Macarena
Department Name
Medical Oncology
Contact Person Name
Fernando Henao
Contact Person Email
ferheca@gmail.com

Germany

Earliest CTIS Part Ii Submission Date
24-04-2026
Latest Decision Or Authorization Date
08-05-2026
Processing Time Days
14
Number Of Sites
12
Number Of Participants
40

Sites

Site Name
Gemeinschaftspraxis Haematologie Onkologie
Department Name
Oncology
Contact Person Name
Thomas Illmer
Contact Person Email
illmer@onkologie-dresden.net
Site Name
Marien Hospital Witten
Department Name
Senology
Contact Person Name
Monika Graeser
Site Name
Staedtisches Klinikum Dessau
Department Name
Obstetrics and Gynecology
Contact Person Name
Hermann Voss
Site Name
DBZ Onkologie GmbH
Department Name
Oncology
Contact Person Name
Antje Mueller
Contact Person Email
kontakt@dasbrustzentrum.de
Site Name
Klinikum Worms gGmbH
Department Name
Obstetric, Gynecology, Senology and Oncology
Contact Person Name
Matthias Koegel
Site Name
Goethe University Frankfurt
Department Name
Breast Oncology
Contact Person Name
Christine Solbach
Contact Person Email
csolbach@med.uni-frankfurt.de
Site Name
Mammazentrum Hamburg MVZ GbR
Department Name
Breast Oncology
Contact Person Name
Anne-Sophie Adam
Contact Person Email
adam@mammazentrum.eu
Site Name
Klinikum Esslingen GmbH
Department Name
Gynecology and Obstetrics
Contact Person Name
Alexander Hein
Site Name
Helios Universitaetsklinikum Wuppertal
Department Name
Senology
Contact Person Name
Vesna Bjelic-Radisic
Site Name
Institut Fuer Versorgungsforschung In Der Onkologie GbR
Department Name
Medical Oncology
Contact Person Name
Rudolf Weide
Contact Person Email
weide@invo-koblenz.de
Site Name
Überörtliche Berufsausübungsgemeinschaft
Department Name
Oncology
Contact Person Name
Andreas Diel
Contact Person Email
diel@onkologie-rheinsieg.de
Site Name
Haematologie-Onkologie im Zentrum MVZ GmbH
Department Name
Hematology- Oncology
Contact Person Name
Berhard Heinrich

Sponsor

Primary sponsor

Full Name
Jazz Pharmaceuticals Ireland Limited
Organisation Type
Pharmaceutical company
Country Of Registered Address
Ireland

Contract research organisations

Name
Sarah Cannon Research Institute LLC
Responsibilities
CRO

Third parties

  • {"country":"United States","full_name":"Sarah Cannon Research Institute LLC","duties_or_roles":"CRO; 5","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"5;6;7","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Target site information; 5","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Translations; 5","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"3;5","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"4;5","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Proofpilot Inc.","duties_or_roles":"Site/Sponsor/Monitor communication platform; 5","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Advarra Inc.","duties_or_roles":"Research Review Services; 5","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Ledger Run Inc.","duties_or_roles":"Site Payments; 5","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
JZP598
Active Substance
ZANIDATAMAB
Modality
Bispecific antibody
Routes Of Administration
IV INJECTION, IV INFUSION
Route
IV INJECTION, IV INFUSION
Authorisation Status
prodAuthStatus: 1
Maximum Dose
2400 mg (maxDailyDoseAmount: 2400 mg)
Investigational Product Name
TRASTUZUMAB EMTANSINE
Active Substance
TRASTUZUMAB EMTANSINE
Modality
ADC
Routes Of Administration
IV INJECTION, IV INFUSION
Route
IV INJECTION, IV INFUSION
Authorisation Status
prodAuthStatus: 2
Maximum Dose
3.6 mg/Kg (maxDailyDoseAmount: 3.6 mg/Kg)
Investigational Product Name
DOCETAXEL
Active Substance
DOCETAXEL
Modality
Small molecule
Routes Of Administration
IV INJECTION, IV INFUSION
Route
IV INJECTION, IV INFUSION
Authorisation Status
prodAuthStatus: 2
Maximum Dose
75 mg/m2 (maxDailyDoseAmount: 75 mg/m2)
Investigational Product Name
TRASTUZUMAB
Active Substance
TRASTUZUMAB
Modality
Monoclonal antibody
Routes Of Administration
IV INJECTION, IV INFUSION
Route
IV INJECTION, IV INFUSION
Authorisation Status
prodAuthStatus: 2
Maximum Dose
8 mg/Kg (maxDailyDoseAmount: 8 mg/Kg)
Investigational Product Name
PACLITAXEL
Active Substance
PACLITAXEL
Modality
Small molecule
Routes Of Administration
IV INJECTION, IV INFUSION
Route
IV INJECTION, IV INFUSION
Authorisation Status
prodAuthStatus: 2
Maximum Dose
80 mg/m2 (maxDailyDoseAmount: 80 mg/m2)
Investigational Product Name
PACLITAXEL ALBUMIN-BOUND
Active Substance
PACLITAXEL ALBUMIN-BOUND
Modality
Small molecule (albumin-bound formulation)
Routes Of Administration
IV INJECTION, IV INFUSION
Route
IV INJECTION, IV INFUSION
Authorisation Status
prodAuthStatus: 2
Maximum Dose
80 mg/m2 (maxDailyDoseAmount: 80 mg/m2)
Investigational Product Name
PERTUZUMAB
Active Substance
PERTUZUMAB
Modality
Monoclonal antibody
Routes Of Administration
IV INJECTION, IV INFUSION
Route
IV INJECTION, IV INFUSION
Authorisation Status
prodAuthStatus: 2
Maximum Dose
840 mg (maxDailyDoseAmount: 840 mg)
Investigational Product Name
CARBOPLATIN
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
IV INJECTION, IV INFUSION
Route
IV INJECTION, IV INFUSION
Authorisation Status
prodAuthStatus: 2
Maximum Dose
DF dosage form 6 (maxDailyDoseAmount: 6 DF dosage form)
Combination Treatment
Yes

Related trials

Other published trials that may interest you.