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HER2+/HR+ Breast CancerPhase 2NCT04224272

Phase 2a Study of ZW25 in Combination With Palbociclib Plus Fulvestrant

A Phase 2 study testing ZW25 (Zanidatamab), Palbociclib and Fulvestrant in people with HER2+/HR+ Breast Cancer, run by Jazz Pharmaceuticals at 13 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multicenter, Phase 2a, open-label, 2-part study to investigate the safety, tolerability, and anti-tumor activity of ZW25 (zanidatamab) in combination with palbociclib plus fulvestrant. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HER2+/HR+ Breast Cancer
What is being tested?
ZW25 (Zanidatamab), Palbociclib and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
13 sitesin 3 countries
Study dates
10 Jun 2020to 30 Jun 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Pathologically-confirmed diagnosis of breast cancer with evidence of locally advanced (unresectable) and/or metastatic disease. All patients in both Parts 1 and 2 must have HER2-positive and HR-positive disease.
  • Received prior treatment with trastuzumab, pertuzumab, AND ado-trastuzumab emtansine (T-DM1); disease progression during or after the most recent prior therapy. Patients in any part of the study who did not receive pertuzumab or T-DM1 because of lack of access (e.g., due to insurance coverage or because they were treated prior to regulatory agency approval of the agent in a relevant indication) or due to medical ineligibility for treatment with T-DM1 (e.g., history of severe infusion reactions to trastuzumab, >/= Grade 2 peripheral neuropathy, or platelet count < 100 x 10^9/L) may be eligible for the study. Prior treatment with endocrine therapy in the neoadjuvant, adjuvant, and/or metastatic setting is permitted.
  • Sites of disease assessible per RECIST version 1.1 (both measurable and non-measurable disease allowed)
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
  • Adequate organ function
  • Adequate cardiac left ventricular function, as defined by left ventricular ejection fraction (LVEF) >/= institutional standard of normal

Who cannot join

  • Prior treatment with trastuzumab, pertuzumab, lapatinib, T-DM1, or other anti-HER2-targeted therapy </= 3 weeks before the first dose of ZW25
  • Prior treatment with chemotherapy, other anti-cancer therapy not otherwise specified, or hormonal cancer therapy </= 3 weeks before the first dose of ZW25
  • Prior treatment with palbociclib or any other CDK4/6 inhibitor, including experimental agents
  • History of myocardial infarction or unstable angina within 6 months prior to enrollment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, or any history of symptomatic congestive heart failure (CHF)
  • QTc Fridericia (QTcF) > 470 ms
  • Grade 2 or greater pneumonitis and/or interstitial lung disease, including pulmonary fibrosis, or other clinically significant infiltrative pulmonary disease not related to lung metastases
Show all 13Show fewer
  • Active hepatitis B or hepatitis C infection
  • Acute or chronic uncontrolled renal disease, pancreatitis, or severe liver disease (Child-Pugh Class C)
  • Known infection with Human Immunodeficiency Virus (HIV)-1 or HIV-2 (Exception: patients with well controlled-HIV [e.g., cluster of differentiation 4 (CD4)-positive T-cell count > 350 mm3 and undetectable viral load] are eligible.)
  • Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
  • Brain metastases: Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks of start of study treatment. Stable, treated brain metastases are allowed (defined as patients who are off steroids and anticonvulsants and are neurologically stable for at least 1 month at the time of screening).
  • History of or ongoing leptomeningeal disease
  • Grade 3 or greater peripheral neuropathy

Trial locations and contacts

13 sites in 3 countries.

13 sites in 3 countries

Spain6 sites

  • Hospital Universitario Vall d'Hebrón

    Barcelona, 08035

  • Hospital General Universitario de Elche

    Elche, Alicante, 03203

  • Hospital Ruber Internacional

    Madrid, 28034

  • Hospital Universitario Virgen de la Victoria

    Málaga, 29010

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

Canada4 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N4N2

  • Jewish General Hospital

    Montreal, Quebec, H3T1E2

  • The Ottawa Hospital Cancer Centre

    Ottawa, Ontario, K1H 8L6

  • Sunnybrook Research Institute

    Toronto, Ontario, M4N3M5

Other trials in Canada

United States3 sites

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • UCLA Hematology/Oncology Parkside

    Santa Monica, California, 90404

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Study of ZW25 (Zanidatamab) With Palbociclib Plus Fulvestrant in Patients With HER2+/HR+ Advanced Breast Cancer

This is a multicenter, Phase 2a, open-label, 2-part study to investigate the safety, tolerability, and anti-tumor activity of ZW25 (zanidatamab) in combination with palbociclib plus fulvestrant. Eligible patients include those with locally advanced (unresectable) and/or metastatic human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor (HR)-positive breast cancer.

Read the detailed description

Part 1 of the study will first evaluate the safety and tolerability of ZW25 in combination with palbociclib plus fulvestrant and will confirm the recommended doses (RDs) of ZW25 and palbociclib in this combination. Part 2 of the study will evaluate the anti-tumor activity of the combination of ZW25 with palbociclib plus fulvestrant at the RD level in patients with HER2-positive, HR-positive advanced breast cancer.

Being tested
ZW25 (Zanidatamab), Palbociclib, Fulvestrant
Keywords
HER2, HR, Bispecific antibody, Biparatopic antibody, Immunotherapy, Breast cancer, Chemotherapy, Palbociclib, Fulvestrant
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZW25 (Zanidatamab)Drug

    Administered intravenously

  • PalbociclibDrug

    Administered orally

  • FulvestrantDrug

    Administered as an intramuscular injection

Study groups in NCT04224272
Study groupRoleWhat they receive
ZW25 (zanidatamab) + palbociclib + fulvestrantExperimentalParticipants who received intravenous dose of 20 mg/kg ZW25 (zanidatamab) every 2 weeks (Q2W) in combination with an oral administration of 125 mg palbociclib once daily from Days 1 to 21, and an intramuscular injection of 500 mg fulvestrant Q2W for 3 doses (Cycle 1 Days 1 and 15 and Cycle 2 Day 1), and every 4 weeks (Q4W) thereafter.
Receives: Drug: ZW25 (Zanidatamab); Drug: Palbociclib; Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose-Limiting Toxicities

    Dose-limiting toxicities, defined using NCI CTCAE version 5.0, are events that 1) occur following administration of ZW25, palbociclib, and fulvestrant; and 2) meet the criteria as specified in the protocol.

    Measured: Cycle 1 Day 1 to Day 28 (each cycle is 28 days)

  2. Number of Participants Reporting Grade 3 or Higher Treatment-emergent Adverse Events

    A treatment-emergent adverse event occurs after the start of study treatment and is defined as any unfavorable or unintended symptom, sign, or disease (including abnormal lab) temporally associated with the use of treatment that may or may not be considered related to treatment. TEAEs were coded using MedDRA v24.0.

    Measured: From the start of dosing of any study drug up until 30 days after last study dose, up to approximately 5 years 20 days.

  3. Progression-free Survival 6

    The progression-free survival at 6 months (PFS6) is a binary endpoint variable based on the progression-free survival (PFS) time, defined as the proportion of participants having PFS time greater than or equal to 24 weeks (168 days).

    Measured: 6 months from first dose of all study drugs to the date of documented disease progression or death

Secondary outcomes (10)

  1. Number of Participants Reporting Any Treatment-emergent Adverse Event, Serious Adverse Event, and Adverse Event of Special Interest

    A treatment-emergent adverse events (TEAEs) was defined as an adverse event (AE) with onset on or after 1st dose of study treatment through 30 days after final dose of study treatment inclusive. An AE is classified as a serious adverse event (SAE) if fatal, life threatening, requires hospitalization, is disabling/incapacitating, causes congenital anomaly or birth defect, and medically significant.

    Adverse events of special interest (AESI) include absolute decrease in LVEF greater than or equal to 10 percentage points from baseline and LVEF value less than 50% post-baseline or LVEF value greater than or equal to 20% to less than or equal to 39% post baseline, symptomatic heart failure, infusion-related reactions, and all greater than or equal to Grade 2 events of pneumonitis and/or interstitial lung disease, including pulmonary fibrosis.

    Measured: From the start of dosing of any study drug up until 30 days after last study dose, up to approximately 5 years 20 days

  2. Maximum Serum Concentration Steady State of ZW25

    Pharmacokinetics (PK) were evaluated using noncompartmental analysis (NCA).

    Measured: End of ZW25 infusion on Cycle 4 Day 1 (steady state) (each cycle is 28 days)

  3. Trough Concentration Steady State of ZW25

    Pharmacokinetics (PK) were evaluated using noncompartmental analysis (NCA).

    Measured: Predose at Cycle 4 Day 1 (steady state) (each cycle is 28 days)

  4. Number of Participants With Anti-drug Antibodies (ADAs) Post-baseline

    Participants were considered to be ADA positive if they were initially ADA negative at baseline and tested positive for ADAs following study drug exposure ("treatment-induced ADA response"), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 4-fold greater than the titer of the baseline sample ("treatment-enhanced ADA response").

    Participants were considered to be ADA negative if they were ADA negative at baseline and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that was at least 4-fold greater than the titer of the baseline sample ("treatment-unaffected ADA").

    Measured: Predose at Cycle 1 Days 1 and 15; Cycle 2 Days 1 and 15; Cycle 4 Day 1 and subsequent ADA assessment visits; end of treatment; 30 days post last dose (safety FU); and every 8 weeks (efficacy FU) (each cycle, 28 days), up to approximately 5 years 20 days.

  5. Objective Response Rate

    Confirmed objective response rate is defined as the number of patients with confirmed complete response (CR) and confirmed partial response (PR). CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions as assessed by the Investigator per RECIST v1.1.

    Measured: From first dose of treatment up to end of study, approximately 5 years 20 days

  6. Duration of Response

    DOR is defined as the time from the first confirmed objective response (CR or PR) to documented PD per RECIST 1.1 or death within 30 days of last dose of study drug (ZW25, palbociclib, and/or fulvestrant) from any cause. Only participants who achieved a confirmed objective response were included in the analysis.

    Measured: From first dose of treatment up to end of study, approximately 5 years 20 days

  7. Disease Control Rate

    Disease control is defined as a best response of CR, PR, non-CR/non-PD (for participants who have only non-target lesions), or SD per RECIST 1.1. The proportion of participants who achieve a disease control response was calculated.

    Measured: From first dose of treatment up to end of study, approximately 5 years 20 days

  8. Progression-free Survival

    Progression-free survival (PFS) time is defined as the time from first dose of ZW25, palbociclib, and/or fulvestrant to the date of first documented disease progression (per RECIST 1.1) or death from any cause, whichever occurs first.

    Measured: From first dose of treatment up to end of study, approximately 5 years 20 days

  9. Overall Survival

    OS is defined as time from first dose of ZW25, palbociclib, and/or fulvestrant until death from any cause.

    Measured: From first dose of treatment up to end of study, approximately 5 years 20 days

  10. Incidence of Abnormal Hepatic Lab Values

    Measured: From first dose of treatment up to end of study, approximately 5 years 20 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2020
  2. Study start10 Jun 2020
  3. Primary completion28 Apr 2023
  4. Study completion30 Jun 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04224272
Sponsor's protocol ID
ZWI-ZW25-202
Other IDs
2019-002956-18, 2019
Status last verified
Aug 2026
First submitted
7 Jan 2020
Last updated
24 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Escriva-de-Romani S, Cejalvo JM, Alba E, Friedmann J, Rodriguez-Lescure A, Savard MF, Pezo RC, Gion M, Ruiz-Borrego M, Hamilton E, Pluard T, Webster M, Beeram M, Linden H, Saura C, Shpektor D, Salim B, Harvey P, Hurvitz SA. Zanidatamab plus palbociclib and fulvestrant in previously treated patients with hormone receptor-positive, HER2-positive metastatic breast cancer: primary results from a two-part, multicentre, single-arm, phase 2a study. Lancet Oncol. 2025 Jun;26(6):745-758. doi: 10.1016/S1470-2045(25)00140-8. Epub 2025 May 5.

    PubMed 40339592

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ZW25 (Zanidatamab), Palbociclib and Fulvestrant in people with HER2+/HR+ Breast Cancer, run by Jazz Pharmaceuticals at 13 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Spain, Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-Limiting Toxicities (time frame: Cycle 1 Day 1 to Day 28 (each cycle is 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04224272, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.

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