Phase Ib/II Study of Zanidatamab Plus Tucatinib and Chemotherapy in HER2-Positive Advanced Breast Cancer

NCT07494448 | Not Yet Recruiting Phase 1 DMC

• 2 other identifiers: MEDOPP07762025-524613-89-00
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

The JAZMINE study is a multicenter, open-label, non-comparative, phase Ib/II clinical trial to evaluate safety and preliminary efficacy of zanidatamab in combination with tucatinib and chemotherapy (capecitabine or eribulin mesylate) in HER2-positive advanced breast cancer.

Conditions

HER 2 Positive Advanced Breast Cancer; Breast Cancer

Keywords

Advanced HER 2 positive; Zanidatamab; Tucatinib; JAZMINE; Chemotherapy

Outcome Measures

Primary Outcomes (2)

• To determine the recommended phase II dose (RP2D) of zanidatamab in combination with tucatinib and capecitabine in participants with HER2-positive ABC (Cohort A).

  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). Note: To identify the recommended dose, other available data from secondary endpoints may be taken into consideration.

  24 days

• To determine the recommended phase II dose (RP2D) of zanidatamab in combination with tucatinib and eribulin in participants with HER2-positive ABC (Cohort B).

  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).

  24 days

Secondary Outcomes (6)

• To assess the preliminary efficacy of capecitabine-based therapy (Cohort A) and eribulin-based therapy (Cohort B) in combination with zanidatamab and tucatinib in terms of Investigator-assessed ORR in participants with HER2-positive ABC.

  Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).

• To assess the preliminary efficacy of capecitabine-based therapy (Cohort A) and eribulin-based therapy (Cohort B) in combination with zanidatamab and tucatinib in terms of Investigator-assessed IC-ORR in participants with HER2-positive ABC.

  Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).

• To assess the preliminary efficacy of capecitabine-based therapy (Cohort A) and eribulin-based therapy (Cohort B) in combination with zanidatamab and tucatinib in terms of Investigator-assessed PFS in participants with HER2-positive ABC.

  Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).

• To assess the preliminary efficacy of capecitabine-based therapy (Cohort A) and eribulin-based therapy (Cohort B) in combination with zanidatamab and tucatinib in terms of Investigator-assessed IC-PFS in participants with HER2-positive ABC

  Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).

• To determine the safety and toxicity profile according to the NCI-CTCAE v.5.0 of capecitabine-based therapy in combination with zanidatamab and tucatinib in participants with HER2-positive ABC (Cohort A).

  Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).

Study Arms (2)

Zanidatamab and tucatinib in combination with capecitabine

EXPERIMENTAL

After confirmation of eligibility and enrollment into the clinical trial, participants will be assigned to one of the treatment cohorts based on local investigator assessment and slots availability. Participants will receive zanidatamab (1800 mg \[participants \<70 kg\] or 2400 mg \[participants ≥70 kg\] intravenous \[IV\] each three weeks \[Q3W\]), and tucatinib (300 mg per oral \[PO\] twice daily \[BID\]) plus increasing doses of capecitabine (750 mg/m2, or 1000 mg/m2 PO BID for the first 14 days of each 21-day cycle). If the 750 mg/m2 dose is not well tolerated, it will be de-escalated to 650 mg/m2. Treatment will continue until disease progression, participant's withdrawal, death, or discontinuation for any other reason unless premature discontinuation of the Study, whichever occurs first.

Drug: Zanidatamab; Drug: Tucatinib; Drug: Capecitabine

Zanidatamab and tucatinib in combination with eribulin

EXPERIMENTAL

After having confirmed eligibility and enrollment into the clinical trial, participants will receive zanidatamab and tucatinib at the same doses as Cohort A, plus increasing doses of eribulin (1.1 mg/m2, or 1.4 mg/m2 IV on days 1 and 8 of each 21-day cycle). If the 1.1 mg/m2 dose is not well tolerated, it will be de-escalated to 0.7 mg/m2. Treatment will continue until disease progression, participant's withdrawal, death, or discontinuation for any other reason unless premature discontinuation of the Study, whichever occurs first.

Drug: Zanidatamab; Drug: Tucatinib; Drug: Eribulin Mesilate injection

Interventions

Zanidatamab DRUG

Will be administered as an intravenous (IV) infusion on Day 1 of each 21-day treatment cycle (Q3W). The dose of zanidatamab will be weight-based: 1800 mg for participants weighing \<70 kg and 2400 mg for participants weighing ≥70 kg. During phase Ib, the dose of zanidatamab will remain constant.

Also known as: JZP598

Zanidatamab and tucatinib in combination with capecitabine; Zanidatamab and tucatinib in combination with eribulin

Tucatinib DRUG

Will be administered orally at a dose of 300 mg twice daily (BID) on a continuous basis throughout each 21-day treatment cycle. During phase Ib, the dose of tucatinib will remain constant.

Also known as: ONT-380, Tukysa

Zanidatamab and tucatinib in combination with capecitabine; Zanidatamab and tucatinib in combination with eribulin

Capecitabine DRUG

Will be administered orally twice daily (PO BID) on Days 1-14 of each 21-day treatment cycle during phase Ib. Dose escalation will be performed with a starting dose of 750 mg/m² PO BID, with escalation to 1000 mg/m² PO BID based on tolerability. If the 750 mg/m² dose is not well tolerated, capecitabine will be de-escalated to 650 mg/m² PO BID.

Zanidatamab and tucatinib in combination with capecitabine

Eribulin Mesilate injection DRUG

Will be administered intravenously on Days 1 and 8 of each 21-day treatment cycle during phase Ib. Dose escalation will be performed with a starting dose of 1.1 mg/m², with escalation to 1.4 mg/m² based on tolerability. If the 1.1 mg/m² dose is not well tolerated, eribulin will be de-escalated to 0.7 mg/m².

Zanidatamab and tucatinib in combination with eribulin

Eligibility Criteria

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

You may qualify if:

• Participants 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.
• Female or male participants ≥ 18 years of age at the time of signing the ICF.
• ECOG PS of 0-1.
• Minimum life expectancy of ≥ 12 weeks at screening.
• 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.
• 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.
• Evaluable disease by RECIST v.1.1.
• 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.
• Note: If no archived sample is available participant eligibility should be discussed with the Medical Monitor.
• Able to provide blood samples at the established time points.
• 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. Transfusion must be ≥ 14 days prior to starting therapy to establish adequate hematologic parameters independent of transfusion support. Participants with chronic anemia (other than autoimmune hemolytic anemia) that is supported by intermittent red blood cell transfusions are eligible.
• 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 (Note: Warfarin and other coumarin derivatives are prohibited).
• 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 calculated per institutional guidelines.

You may not qualify if:

• Participation in another clinical trial, interventional or observational, until the Study's safety visit.
• Note: Participation in retrospective studies or data analysis is allowed.
• 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.
• Note: For palliative non-CNS radiotherapy, a shorter washout period may be acceptable. This should be evaluated on a case-by-case basis and discussed with the medical monitor.
• Prior treatment with capecitabine and eribulin.
• Known or suspected leptomeningeal disease (LMD) as documented by the investigator.
• Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term (including massive uncontrolled effusions \[pleural, pericardial, peritoneal\] or pulmonary lymphangitis).
• Receipt of a live vaccine within 4 weeks prior to enrollment.
• History of prior allogeneic bone marrow, stem cell, or solid organ transplantation.
• 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.
• Requirement for ongoing therapy with any prohibited medications listed in the protocol.

Sponsors & Collaborators

• MedSIR: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

zanidatamab; tucatinib; Capecitabine; eribulin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

MEDSIR

CONTACT

+ 34 932 214 135; contact.trials@medsir.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A multicenter, open-label, non-comparative, phase Ib/II clinical trial. The phase Ib will be a non-randomized, two-cohort chemotherapy dose-ranging study with a Bayesian optimal interval (BOIN) design. The phase II will be a randomized (2:1), two-arm efficacy and safety study.

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: March 27, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): May 31, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share