ZANIDATAMAB for HER2-positive advanced breast cancer | Breast cancer

Inclusion criteria

• {"criterion_text":"- PHASE Ib: Participants, or legal representative (if applicable) must be capable of understanding the purpose of the Study and have signed a written informed consent form (ICF) prior to beginning specific protocol procedures."}
• {"criterion_text":"- PHASE Ib: Able to provide blood samples at the established time points."}
• {"criterion_text":"- PHASE Ib: Participant must have adequate bone marrow, coagulation, liver, and renal function: Absolute neutrophil count (ANC) ≥ 1.5 × 103/μL, platelet count ≥ 100 x 103/μL, and hemoglobin (Hgb) ≥ 9 g/dL. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × the upper limit of normal (ULN), unless on medication known to alter INR and aPTT. Total bilirubin ≤ 1.5 × ULN or ≤ 3.0 × ULN for participants with Gilbert’s disease (if the conjugated bilirubin is ≤ 1.5 × ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN (for participants with liver metastases, AST and ALT ≤ 5.0 × ULN are acceptable). Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min"}
• {"criterion_text":"- PHASE Ib: Female participants of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of Study treatments."}
• {"criterion_text":"- PHASE Ib: Female participants of childbearing potential and male participants with a partner of childbearing potential must agree to use two methods of birth control with a failure rate of less than 1% per year starting at the screening, throughout the study, and for 12 months after the last dose of Study treatments."}
• {"criterion_text":"- PHASE Ib: Female participants must refrain from oocyte donation and breastfeeding, and male participants must not donate or bank sperm starting at the screening, throughout the study, and for 12 months after the last dose of Study treatments."}
• {"criterion_text":"- PHASE Ib: Participants must be accessible for treatment and follow-up visits."}
• {"criterion_text":"- PHASE Ib: Specific inclusion criteria for BMs: 1. Stable BMs were defined as BMs radiographically stable for ≥4 weeks since completion of treatment."}
• {"criterion_text":"- PHASE Ib: Specific inclusion criteria for BMs: 2. Untreated BM without immediate need for local therapy. For participants with untreated CNS lesions > 2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment."}
• {"criterion_text":"- PHASE Ib: Specific inclusion criteria for BMs: 3. BMs that had progressed since local CNS therapy, with no clinical indication for immediate retreatment with local therapy."}
• {"criterion_text":"- PHASE Ib: Specific inclusion criteria for BMs: 4. Washout periods before the first day of dosing were >7 days for SRS or gamma knife, and >24 days for WBRT, respectively. The use of systemic corticosteroids for control of symptoms of BM is not permitted if the total daily dose is > 2 mg of dexamethasone (or equivalent). However, participants on a chronic stable dose of ≤ 2 mg total daily of dexamethasone (or equivalent) may be eligible following discussion and approval by the medical monitor. Participants receiving an anticonvulsant therapy must be on stable dosing regimen for ≥ 14 days prior to the first dose of Study treatment."}
• {"criterion_text":"- PHASE Ib: Female or male participants ≥ 18 years of age at the time of signing the ICF."}
• {"criterion_text":"- At least 50% of participants enrolled in phase II must have BMs."}
• {"criterion_text":"- PHASE Ib: ECOG PS of 0-1."}
• {"criterion_text":"- PHASE Ib: Minimum life expectancy of ≥ 12 weeks at screening."}
• {"criterion_text":"- PHASE Ib: Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent."}
• {"criterion_text":"- PHASE Ib: Locally confirmed HER2-positive breast cancer (immunohistochemistry [IHC] score of 3+ or ICH score of 2+ with confirmation of HER2 amplification by in situ hybridization [ISH]) per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 criteria on the most recent analyzed biopsy."}
• {"criterion_text":"- PHASE Ib: Evaluable disease by RECIST v.1.1."}
• {"criterion_text":"- PHASE Ib: All participants need to have experienced disease progression after at least one line, but no more than 3 lines, of anti-HER2-therapy for advanced disease."}
• {"criterion_text":"- PHASE Ib: Able to provide the most recently available FFPE tumor tissue blocks at the time of inclusion."}

Exclusion criteria

• {"criterion_text":"- PHASE Ib: Participation in another clinical trial, interventional or observational, until the Study's safety visit."}
• {"criterion_text":"- PHASE Ib: Known allergy or hypersensitivity reaction to any investigational medicinal products (IMPs) or their incorporated substances, including life-threatening hypersensitivity to monoclonal antibodies or excipients in zanidatamab."}
• {"criterion_text":"- PHASE Ib: Ongoing, clinically significant toxicity associated with prior cancer therapies that has not resolved to ≤ Grade 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0) (except for alopecia or other toxicities not considered a safety risk for the participant at the investigator's discretion)."}
• {"criterion_text":"- PHASE Ib: Has a concurrent malignancy or malignancy within 5 years of Study enrollment except for carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor’s medical monitor is required."}
• {"criterion_text":"- PHASE Ib: Major surgical procedure or significant traumatic injury within 4 weeks before the first dose of Study treatment or anticipation of the need for major surgery within the course of the Study treatment."}
• {"criterion_text":"- PHASE Ib: Have clinically significant cardiac disease such as: Ventricular arrhythmia requiring therapy, uncontrolled hypertension (defined as persistent systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg on antihypertensive medications), any history of symptomatic congestive heart failure (CHF) classified as New York Heart Association (NYHA) Class II to IV, or any Grade ≥2 CHF related to prior therapy. Participants with Grade 1 CHF from prior treatment are eligible only if the condition has fully resolved at the time of screening, presence of ≥ Grade 2 QTc prolongation on screening electrocardiogram (ECG), conditions potentially resulting in drug-induced prolongation of the QT interval or torsade de pointes: (Congenital or acquired long QT syndrome, family history of sudden death, history of previous drug induced QT prolongation, current use of medications with known and accepted associated risk of QT prolongation). Myocardial infarction or unstable angina within 6 months prior to first dose of study treatment, Left ventricular ejection fraction (LVEF) < 50% as determined by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose of Study treatments."}
• {"criterion_text":"- PHASE Ib: Having a history of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening."}
• {"criterion_text":"- PHASE Ib: Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months of the Study enrolment, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, post COVID-19 pulmonary fibrosis, etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy."}
• {"criterion_text":"- PHASE Ib: Having peripheral neuropathy ≥ Grade 2."}
• {"criterion_text":"- PHASE Ib: Known history of clinically significant bleeding, thrombosis, intestinal obstruction, or gastrointestinal perforation within 3 months of study initiation."}
• {"criterion_text":"- PHASE Ib: Known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Participants with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Participants positive for HCV antibody are eligible only if the polymerase chain reaction (PCR) is negative for HCV RNA."}
• {"criterion_text":"- PHASE Ib: Have received treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation, or experimental agent within ≤ 3 weeks prior to the first dose of Study treatments."}
• {"criterion_text":"- PHASE Ib: Known infection with Human Immunodeficiency Virus (HIV). (Participants with HIV on antiretroviral therapy (ART) with well-controlled HIV infection/disease are allowed, participants on ART must have a CD4+ T-cell count ≥ 350 cells/mm3 at time of screening, participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening, participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to Study entry, the combination of the ART regimen must not contain any medications that may interfere with the Study treatments)."}
• {"criterion_text":"- PHASE Ib: Other systemic uncontrolled infection at the time of enrollment."}
• {"criterion_text":"- PHASE Ib: Having known dihydropyridine dehydrogenase deficiency (DPD). This must be checked before treatment with capecitabine, according to current guidelines."}
• {"criterion_text":"- PHASE Ib: Having an inability to swallow pills or significant gastrointestinal disease, which would preclude the adequate oral absorption of medications."}
• {"criterion_text":"- PHASE Ib: Any other serious medical condition and/or abnormality in clinical laboratory tests that, in the Investigator's judgment, precludes the participant's safe participation in and completion of the Study."}
• {"criterion_text":"- PHASE II: Prior treatment with HER2 tyrosine kinase inhibitors (TKIs)."}
• {"criterion_text":"- PHASE Ib: Prior treatment with capecitabine and eribulin."}
• {"criterion_text":"- PHASE Ib: Known or suspected leptomeningeal disease (LMD) as documented by the investigator."}
• {"criterion_text":"- PHASE Ib: Advanced, symptomatic, visceral spread that is at risk of lifethreatening complications in the short term (including massive uncontrolled effusions [pleural, pericardial, peritoneal] or pulmonary lymphangitis)."}
• {"criterion_text":"- PHASE Ib: Receipt of a live vaccine within 4 weeks prior to enrollment."}
• {"criterion_text":"- PHASE Ib: History of prior allogeneic bone marrow, stem cell, or solid organ transplantation."}
• {"criterion_text":"- PHASE Ib: The washout periods for prior anticancer therapies before randomization are as follows: Prior therapies with chemotherapy and/or monoclonal antibodies including ADCs: washout period up to 3 weeks. Prior therapies with small molecule targeted therapies: washout period of ≤ 2 weeks or 5 half-lives, whichever is shorter. No washout period needed for endocrine therapy. No washout period for gonadotropin-releasing hormone agonists."}
• {"criterion_text":"- PHASE Ib: Requirement for ongoing therapy with any prohibited medications listed in the protocol."}

Primary endpoints

• {"endpoint_text":"- PHASE Ib: The maximum tolerated dose (MTD) of zanidatamab administered in combination with tucatinib and capecitabine, as determined by the proportion of DLTs observed. The RP2D will be established based on the MTD, the overall safety and tolerability profile and early efficacy data (Cohort A).","definition_or_measurement_approach":"MTD determined by proportion of dose-limiting toxicities (DLTs) observed; RP2D established using MTD plus overall safety, tolerability and early efficacy data."}
• {"endpoint_text":"- PHASE Ib: The MTD of zanidatamab administered in combination with tucatinib and eribulin, as determined by the proportion of DLTs observed. The RP2D will be established based on the MTD, the overall safety and tolerability profile and early efficacy data (Cohort B)..","definition_or_measurement_approach":"MTD determined by proportion of DLTs observed; RP2D established based on MTD, safety, tolerability and early efficacy."}
• {"endpoint_text":"- PHASE II: PFS, defined as the period from treatment initiation to the first occurrence of documented radiographic disease progression or death from any cause, whichever occurs first, as assessed by the Investigator per RECIST v.1.1 (Arm A).","definition_or_measurement_approach":"Progression-free survival (PFS) measured from treatment start to first documented radiographic progression or death; investigator assessment per RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- PHASE Ib: ORR, defined as the number of participants with CR or PR, divided by the number of participants in the analysis population, as assessed by the Investigator per RECIST v.1.1 (Cohort A and B)","definition_or_measurement_approach":"Objective response rate (ORR): proportion with complete response (CR) or partial response (PR) per Investigator assessment using RECIST v1.1."}
• {"endpoint_text":"- PHASE Ib: IC-ORR, defined as the percentage of participants with IC CR or PR, divided by the number of participants in the analysis population, assessed by the Investigator per RANO-BM criteria (Cohort A and B only in participants with BM).","definition_or_measurement_approach":"Intracranial objective response rate assessed by RANO-BM criteria for participants with brain metastases."}
• {"endpoint_text":"- PHASE Ib: PFS, defined as the period from Study treatment initiation to the first occurrence of documented radiographic disease progression or death from any cause, whichever occurs first, as assessed by the investigator using RECIST v.1.1. criteria (Cohort A and B).","definition_or_measurement_approach":"PFS measured from treatment initiation to radiographic progression or death per RECIST v1.1 by investigator."}
• {"endpoint_text":"- PHASE Ib: IC-PFS, defined as the period from treatment initiation to the first occurrence of documented radiographic intracranial progression or death from any cause, whichever occurs first, as assessed by the Investigator per RANO-BM criteria. (Cohort A and Bonly in participants with BM)","definition_or_measurement_approach":"Intracranial PFS measured from treatment start to intracranial radiographic progression or death per RANO-BM."}
• {"endpoint_text":"- PHASE II: IC-PFS, defined as the period from treatment initiation to the first occurrence of documented radiographic intracranial progression or death from any cause, whichever occurs first, as assessed by the Investigator per RANO-BM criteria (Arm A and B only in participants with BM).","definition_or_measurement_approach":"Intracranial PFS per RANO-BM for participants with brain metastases."}
• {"endpoint_text":"- PHASE II: IC-ORR at 3 months, defined as the percentage of participants with intracranial complete response (CR) or partial response (PR), divided by the number of participants in the analysis population, as assessed by the Investigator per RANO-BM criteria (Arm A and Arm B; only in participants with BM)..","definition_or_measurement_approach":"Intracranial ORR at 3 months per RANO-BM for participants with brain metastases."}
• {"endpoint_text":"- PHASE II: ORR, defined as the number of participants with CR or PR, divided by the number of participants in the analysis population, as assessed by the Investigator per RECIST v.1.1 (Arm A and Arm B).","definition_or_measurement_approach":"ORR per RECIST v1.1 by investigator for overall lesions."}
• {"endpoint_text":"- PHASE II: PFS, defined as the period from Study treatment initiation to the first occurrence of documented radiographic disease progression or death from any cause, whichever occurs first, as assessed by the investigator using RECIST v.1.1. criteria (Arm B).","definition_or_measurement_approach":"PFS per RECIST v1.1 by investigator."}
• {"endpoint_text":"- PHASE II: TTR, defined as the period from start of treatment to time of the first objective tumor response (tumor shrinkage of ≥ 30%) observed for participants who achieved a best overall response of CR or PR, based on local Investigator assessment as per RECIST v.1.1 overall lesions (Arm A and Arm B)","definition_or_measurement_approach":"Time to response measured from treatment start to first objective tumor response (≥30% shrinkage) per RECIST v1.1 by investigator."}
• {"endpoint_text":"- PHASE II: DoR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, based on local Investigator assessment as per RECIST v.1.1 overall lesions (Arm A and Arm B).","definition_or_measurement_approach":"Duration of response measured from first documented objective response to progression or death per RECIST v1.1 by investigator."}
• {"endpoint_text":"- PHASE II: CBR, defined as the rate of participants with an objective response (CR or PR), or stable disease for at least 24 weeks, based on local Investigator assessment as per RECIST v.1.1 overall lesions (Arm A and Arm B)..","definition_or_measurement_approach":"Clinical benefit rate: CR or PR or stable disease ≥24 weeks per RECIST v1.1 by investigator."}
• {"endpoint_text":"- PHASE II: Best percentage change from baseline in the size of target lesion (RECIST v.1.1 assessment performed by CT). The best percentage change is defined as the biggest decrease, or the smallest increase if no decrease (Arm A and Arm B)..","definition_or_measurement_approach":"Best percentage change from baseline in target lesion size measured by CT per RECIST v1.1."}

Methods

• K1 Recruitment arrangements (document present) - local site-based recruitment at hospital oncology centres in Spain
• K2_Recruitment material_Convive con el cancer_ES (patient-facing recruitment material) - advocacy/awareness channel
• K2_Recruitment material_Social networks digital compaings website_ES - digital recruitment via social networks and website

Spain

Earliest CTIS Part Ii Submission Date

15-04-2026

Latest Decision Or Authorization Date

05-05-2026

Processing Time Days

20

Number Of Sites

12

Number Of Participants

129

Primary sponsor

Full Name

Medica Scientia Innovation Research S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

Alcura Health Espana S.A.

Responsibilities

Duties codes: [{"id":1003496,"code":"14"}] (as listed in CTIS third party data); contact laia.novell@alcura-health.es

Name

Evidenze Health Espana S.L.

Responsibilities

Duties codes: [{"id":1003497,"code":"1"},{"id":1003498,"code":"12"},{"id":1003499,"code":"14"},{"id":1003500,"code":"2"},{"id":1003501,"code":"5"},{"id":1003502,"code":"7"}]; contact ensayosclinicos@evidenze.com

Third parties

• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"[{\"id\":1003496,\"code\":\"14\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Evidenze Health Espana S.L.","duties_or_roles":"[{\"id\":1003497,\"code\":\"1\"},{\"id\":1003498,\"code\":\"12\"},{\"id\":1003499,\"code\":\"14\"},{\"id\":1003500,\"code\":\"2\"},{\"id\":1003501,\"code\":\"5\"},{\"id\":1003502,\"code\":\"7\"}]","organisation_type":"Pharmaceutical company"}