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Endometrial CancerPhase 2NCT04513665

ZW25 in Women With Endometrial Cancers

A Phase 2 study testing ZW25 in people with Endometrial Cancer and Carcinosarcoma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Completed

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

Official record
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Trial summary

This study is being done to test the drug ZW25 and look at whether this drug is effective in women with HER2-overexpressed endometrial cancer or carcinosarcoma that has been treated in the past. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Endometrial Cancer, Carcinosarcoma
What is being tested?
ZW25
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
7 sitesUnited States
Study dates
12 Aug 2020to 8 Mar 2024
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must be enrolled or agree to consent to the companion genomic profiling study MSKCC IRB# 12-245 Part A. Results are not required prior to initiating treatment on protocol, unless patients do not have other test results by IHC or FISH confirming HER2 overexpression.
  • Patients must have recurrent or persistent HER2 overexpressing endometrial cancer or endometrial carcinosarcoma. HER2 overexpression is defined as 3+ by IHC or 2+ with gene amplification by FISH (HER2/CEP17 ratio ≥ 2) or HER2 amplified (fold change ≥ 2) on MSK IMPACT.
  • Histologic documentation of diagnosis of endometrial carcinoma or carcinosarcoma is required.
  • Age ≥ 18 years
  • Patients must have had at least one but no more than two prior chemotherapeutic regimens for management of endometrial carcinoma (including neo-adjuvant and/or adjuvant chemotherapy). Initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen. Prior hormonal therapy will not count as a prior regimen. Prior treatment with trastuzumab is allowed.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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  • LVEF ≥ 50% on baseline screening ECHO.
  • Resolution of adverse effects of recent surgery, radiotherapy, or chemotherapy to Grade ≤ 1 prior to first study treatment (with the exception of alopecia or clinically insignificant laboratory values).
  • Patients must have measurable disease. Measurable disease is defined by RECIST (version 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each non-nodal lesion must be 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or 20 mm when measured by chest x-ray. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI.
  • No active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection).
  • All patients must consent to mandatory pre-treatment and post-treatment core needle biopsies.
  • Patients must have adequate hematological, liver, cardiac and kidney function within 14 days prior to first treatment:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)
  • Platelet ≥ 100 X 109/L (>100,000 per mm^3)
  • Hemoglobin ≥ 8.0 g/dL
  • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). (Unless Gilbert's Syndrome, for which Bilirubin ≤ 3 x institutional upper limit of normal (ULN), without concurrent clinically significant liver disease) AST (SGOT)/ALT (SGPT) ≤ 3 x institutional upper limit of normal (ULN) unless liver metastases are present, in which case it must be ≤ 5x ULN.
  • Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN).
  • For patients of childbearing potential, agreement to use two effective forms of contraception (e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants) and to continue its use for the duration of the study and for 12 weeks after the last ZW25 dose.
  • Agree to practice total abstinence when this is in line with the preferred and usual lifestyle of the subject.
  • A woman is considered to be of childbearing potential unless 1 of the following applies: She is considered to be permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, tubal ligation, and bilateral oophorectomy.
  • She is postmenopausal, defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to confirm a postmenopausal state.
  • Female patients of childbearing potential must have a negative serum pregnancy test result less than 3 day prior to administration of the first dose of study treatment.
  • Patients or their legally authorized representative (LAR) must be willing and able to sign the informed consent form, and to adhere to the study visit schedule and other protocol requirements.

Who cannot join

  • Women who are pregnant or lactating or women of childbearing potential (WCBP) not protected by highly-effective contraceptive methods.
  • > Grade 1 peripheral neuropathy.
  • History of hemorrhagic or ischemic stroke within the prior six months.
  • History of NYHA Class II-IV heart failure, no serious arrhythmia.
  • History of MI or unstable angina within 6 months of study initiation.
  • Patients with a lifetime cumulative dose of anthracycline >300 mg/m2 or who have received anthracycline treatment within 90 days of the expected first dose of ZW25 are not eligible for treatment.
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  • Prior hypersensitivity to monoclonal antibodies.
  • Active hepatitis B or hepatitis C infection. Patients with previously resolved hepatitis B infection are eligible. Presence of positive test results for hepatitis B infection who have resolved the infection (defined by positive for HB surface antibody (anti-HBs) and polymerase chain reaction (PCR) assay is negative for HBV DNA are eligible. Patients positive for HCV antibody are eligible only if testing for HCV RNA is negative.
  • Known HIV infection.
  • Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease).
  • Major surgical procedure or significant traumatic injury within 28 days prior to Day 1 or anticipation of the need for major surgery during the course of study treatment.
  • Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) leptomeningeal carcinomatosis.
  • Patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria:
  • Presence of measurable disease outside the CNS
  • No radiographic evidence of worsening upon the completion of CNSdirected therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
  • No history of intracranial hemorrhage or spinal cord hemorrhage
  • No ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants at a stable dose are allowed)
  • Absence of leptomeningeal disease
  • Inability to comply with study and follow-up procedures.
  • Known allergy or hypersensitivity to the components of ZW25 formulation.
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
  • Active or history of inflammatory bowel disease (IBD)
  • Severe infections within 4 weeks prior to initiation of study drug treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible for the study. Patients receiving antibiotic treatment for urinary tract infection are also eligible.
  • Administration of a live attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipated need for such a vaccine during study. Patients must agree not to receive live, attenuated influenza vaccine (e.g., Flumist®) within 4 weeks prior to treatment.)
  • Participation in another clinical study with receipt of an investigational product during the last 4 weeks.
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥ 2 years before the first dose of study drug and of low potential risk for recurrence. b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. c. Adequately treated carcinoma in situ without evidence of disease (e.g., cervical cancer in situ). d. Adequately treated stage 1 breast cancer.
  • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) < 21 days prior to the first dose of study drug. Receipt of the last dose of hormonal therapy within < 7 days prior to the first dose of study drug.
  • Any prior radiation therapy must be discontinued at least four weeks prior to registration.
  • QT interval corrected for heart rate (QTc) ≥ 470 ms on screening electrocardiograms (ECG) using QTC Federica.
  • History of small or large bowel obstruction within 3 months of registration, including subjects with palliative gastric drainage catheters. Subjects with palliative diverting ileostomy or colostomy are allowed if they have been symptom free for more than 3 months.
  • Subjects with refractory ascites, defined as ascites needing drainage catheter or therapeutic paracentesis more often than every 4 weeks.
  • Ongoing bowel perforation or presence of bowel fistula or abscess within 3 months of registration.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Memorial Sloan Kettering Basking Ridge (Limited protocol activities)

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (Limited protocol activities)

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester (Limited protocol activities)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (Limited protocol activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (Limited protocol activities)

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau (Limited protocol activities)

    Rockville Centre, New York, 11570

Other trials in United States

About this study

Official title: A Phase 2 Trial of ZW25 in HER2 Overexpressed Advanced Endometrial Cancers and Carcinosarcomas (ZW25-IST-2)

This study is being done to test the drug ZW25 and look at whether this drug is effective in women with HER2-overexpressed endometrial cancer or carcinosarcoma that has been treated in the past.

Being tested
ZW25
Keywords
Endometrial Cancer, Carcinosarcoma, ZW25, 20-162, Memorial Sloan Kettering Cancer Center
Medical subject headings
Endometrial Neoplasms, Carcinosarcoma

What participants receive

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

  • ZW25Drug

    ZW25 at 20mg/kg intravenously (IV) every two weeks.

Study groups in NCT04513665
Study groupRoleWhat they receive
Stage 1ExperimentalParticipants will have recurrent endometrial carcinoma or carcinosarcoma with HER2 overexpression and 1-2 prior lines of chemotherapy. 16 participants will be accrued. If 2 or greater responses are seen, Stage 2 will accrue additional participants.
Receives: Drug: ZW25
Stage 2ExperimentalIf 2 or greater responses are seen during Stage 1, Stage 2 will accrue an additional 9 participants. Participants will have recurrent endometrial carcinoma or carcinosarcoma with HER2 overexpression and 1-2 prior lines of chemotherapy.
Receives: Drug: ZW25

What is being measured

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

  1. Overall Response Rate/ORR of Participants

    ORR = Compete Response (CR) + Partial Response (PR) by RECIST v 1.1 </= 24 weeks from the start of treatment

    Measured: </= 24 weeks from the start of treatment

Timeline

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

  1. First posted14 Aug 2020
  2. Study start12 Aug 2020
  3. Primary completion8 Mar 2024
  4. Study completion8 Mar 2024

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
Non-randomised
Intervention model
Crossover
Model description
The study will be conducted in two stages. Stage 1 will accrue 16 patients and if two or greater responses are seen, Stage 2 will accrue an additional 9 patients.
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04513665
Sponsor's protocol ID
20-162
Status last verified
Mar 2024
First submitted
12 Aug 2020
Last updated
22 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Publications

  • Lumish M, Chui MH, Zhou Q, Iasonos A, Sarasohn D, Cohen S, Friedman C, Grisham R, Konner J, Kyi C, Rubinstein M, Troso-Sandoval T, Aghajanian C, Makker V. A phase 2 trial of zanidatamab in HER2-overexpressed advanced endometrial carcinoma and carcinosarcoma (ZW25-IST-2). Gynecol Oncol. 2024 Mar;182:75-81. doi: 10.1016/j.ygyno.2023.12.028. Epub 2024 Jan 22.

    PubMed 38262242

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ZW25 in people with Endometrial Cancer and Carcinosarcoma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

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 23 inclusion and 34 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 22 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in 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 21 Oct 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?

Overall Response Rate/ORR of Participants (time frame: </= 24 weeks from the start of treatment). 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 NCT04513665, 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 22 May 2025.

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