ZW25 in Women With Endometrial Cancers

NCT04513665 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 20-162
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Endometrial Cancer; Carcinosarcoma

Keywords

Endometrial Cancer; Carcinosarcoma; ZW25; 20-162; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (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

  </= 24 weeks from the start of treatment

Study Arms (2)

Stage 1

EXPERIMENTAL

Participants 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.

Drug: ZW25

Stage 2

EXPERIMENTAL

If 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.

Drug: ZW25

Interventions

ZW25 DRUG

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

Stage 1; Stage 2

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Zymeworks BC Inc.: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited protocol activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited protocol activities)

Montvale, New Jersey, 07645, United States

Location

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

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited protocol activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited protocol activities)

Rockville Centre, New York, 11570, United States

Location

Related Publications (1)

• 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.

  PMID: 38262242 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Endometrial Neoplasms; Carcinosarcoma

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue

Results Point of Contact

• Title: Dr. Vicky Makker, MD
• Organization: Memorial Sloan Kettering Cancer Center

makkerv@mskcc.org

646-888-4224

Study Officials

• Vikky Makker, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 12, 2020
• First Posted: August 14, 2020
• Study Start: August 12, 2020
• Primary Completion: March 8, 2024
• Study Completion: March 8, 2024
• Last Updated: May 22, 2025
• Results First Posted: October 21, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)