Ended Therapeutic exploratory (Phase II) Breast cancer patients including those with locally advanced (unresectable) or metastatic HER2-positive, HR-positive breast cancer

Study to evaluate the safety and tolerability of ZW25 in combination with palbociclib plus fulvestrant

EU CTIS ID: 2023-508135-30-00

What this study is testing

Part 1 To recommend a dose for ZW25 in combination with palbociclib plus fulvestrant for Part 2 by evaluating the safety and tolerability of ZW25 in combination with palbociclib plus fulvestrant in subjects with locally advanced (unresectable) and/or metastatic human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor (HR)-positive breast cancer Part 2 To evaluate the anti-tumor activity of ZW25 in combination with palbociclib plus fulvestrant in subjects with locally advanced (unresectable) and/or metastatic HER2 positive , HR positive breast cancer

Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1.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 as follows: •HER2 positive based on the HER2 Testing in Breast Cancer: American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Clinical Practice Guidelines (Wolff 2018). •HR positive defined as estrogen-receptor positive (ER positive) and/or progesterone-receptor positive (PgR positive) disease based on the ASCO/CAP Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer (Hammond 2010)."
4.Sites of disease assessable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (both measurable and non-measurable disease allowed)
5.Male and female subjects aged 18 years or older
6.An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
7.Life expectancy of at least 3 months in the opinion of the investigator
8.The following baseline laboratory data: a.Absolute neutrophil count (ANC) ≥ 1.5 x 10E9/L b.Platelet count ≥ 75 x 10E9/L c.Hemoglobin ≥ 9 g/dL d.Prothrombin time (PT) and/or International Normalized Ratio (INR) and partial thromboplastin time (PTT)/ a PTT /activated partial thromboplastin time)≤ 1.5 x upper limit of normal (ULN), unless on medication known to alter the INR or PTT e.Total bilirubin ≤ 1.5 x ULN per institutional values (subjects with known Gilbert's Syndrome may enroll with 2.5 x ULN provided the direct bilirubin is ≤ 1.5 mg/dL) f.Alanine transaminase (ALT) ≤ 3.0 x ULN per institutional values (if liver metastases are present, ≤ 5.0 x ULN) g.Aspartate transaminase (AST) ≤ 3.0 x ULN per institutional values (if liver metastases are present, ≤ 5.0 x ULN) h.Serum creatinine ≤ 1.5 X ULN or calculated glomerular filtration rate 50 mL/min

You likely can't join if

1.Prior treatment with trastuzumab, pertuzumab, lapatinib, T-DM1, or other anti-HER2-targeted therapy ≤ 3 weeks before the first dose of ZW25
3.Prior treatment with experimental biologic and non-biologic therapies ≤ 4 weeks before the first dose of ZW25
4.Prior treatment with radiation therapy other than for central nervous system (CNS) disease ≤ 3 weeks before the first dose of ZW25
5.Treatment with anthracyclines within 90 days before first dose of ZW25 and/or total lifetime load exceeding 360 mg/m2 Adriamycin or equivalent
6.Use of any medications or substances that are strong inhibitors or inducers of CYP3A isoenzymes within 7 days of first dose of any study drug
14.Acute or chronic uncontrolled renal disease, pancreatitis, or severe liver disease (Child-Pugh Class C)

See the full eligibility criteria

Who can join

1.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 as follows: •HER2 positive based on the HER2 Testing in Breast Cancer: American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Clinical Practice Guidelines (Wolff 2018). •HR positive defined as estrogen-receptor positive (ER positive) and/or progesterone-receptor positive (PgR positive) disease based on the ASCO/CAP Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer (Hammond 2010)."
4.Sites of disease assessable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (both measurable and non-measurable disease allowed)
5.Male and female subjects aged 18 years or older
6.An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
7.Life expectancy of at least 3 months in the opinion of the investigator
8.The following baseline laboratory data: a.Absolute neutrophil count (ANC) ≥ 1.5 x 10E9/L b.Platelet count ≥ 75 x 10E9/L c.Hemoglobin ≥ 9 g/dL d.Prothrombin time (PT) and/or International Normalized Ratio (INR) and partial thromboplastin time (PTT)/ a PTT /activated partial thromboplastin time)≤ 1.5 x upper limit of normal (ULN), unless on medication known to alter the INR or PTT e.Total bilirubin ≤ 1.5 x ULN per institutional values (subjects with known Gilbert's Syndrome may enroll with 2.5 x ULN provided the direct bilirubin is ≤ 1.5 mg/dL) f.Alanine transaminase (ALT) ≤ 3.0 x ULN per institutional values (if liver metastases are present, ≤ 5.0 x ULN) g.Aspartate transaminase (AST) ≤ 3.0 x ULN per institutional values (if liver metastases are present, ≤ 5.0 x ULN) h.Serum creatinine ≤ 1.5 X ULN or calculated glomerular filtration rate 50 mL/min
9.Adequate cardiac left ventricular function, as defined by LVEF ≥ institutional standard of normal
10.All toxicity related to prior cancer therapies must have resolved to ≤ XML File Identifier: 2LZ33yYQqmBiBGpwbnSiOMkiyFA= Page 32/51 Grade 1, with the exception of alopecia or ≤ Grade 2 neuropathy
11.If female and of child-bearing potential, must have a negative pregnancy test ≤ 3 days prior to the first dose of ZW25
12.For female subjects who are not surgically sterile or post-menopausal and for male subjects with a partner of child-bearing potential, willingness to use 2 methods of birth control with a failure rate of less than 1% per year during the study and for 12 months after the last dose of study drug (ZW25, palbociclib, and/or fulvestrant). These include, but are not limited to, established use of oral, implanted, or injected hormonal contraceptives; placement of intra-uterine device or intrauterine system; or use of barrier methods, such as condom or diaphragm together with a spermicidal product.
13.Female subjects must agree not to breastfeed or donate ova starting at screening and throughout the study period, and for at least 12 months after the last dose of study drug (ZW25, palbociclib, and/or fulvestrant)
14.Male subjects must not donate sperm starting at screening and throughout the study period, and for at least 12 months after the last dose of study drug (ZW25, palbociclib, and/or fulvestrant)
15.Signed informed consent prior to any study procedures not considered standard of care
2.Able to provide a new formalin-fixed, paraffin-embedded (FFPE) tumor sample (preferred) or archived tumor tissue (most recent sample available) for retrospective central review of HER2 status. Local assessments performed on a new tumor sample or archived tumor tissue in a Clinical Laboratory Improvements Amendments (CLIA)- certified lab using a combination of IHC and ISH/FISH methods may be used to determine HER2 and HR status for study eligibility. IHC must be used to determine HR status. Unless otherwise approved by the sponsor medical monitor, specimens should be provided for centralized retrospective review of HER2 status.
3.Received prior treatment with trastuzumab, pertuzumab, AND adotrastuzumab emtansine (T-DM9); disease progression during or after the most recent prior therapy. Subjects 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 10E9/L) may be eligible for the study after discussion with and approval from the sponsor medical monitor. Prior treatment with endocrine therapy in the neoadjuvant, adjuvant, and/or metastatic setting is permitted.

What rules you out

1.Prior treatment with trastuzumab, pertuzumab, lapatinib, T-DM1, or other anti-HER2-targeted therapy ≤ 3 weeks before the first dose of ZW25
3.Prior treatment with experimental biologic and non-biologic therapies ≤ 4 weeks before the first dose of ZW25
4.Prior treatment with radiation therapy other than for central nervous system (CNS) disease ≤ 3 weeks before the first dose of ZW25
5.Treatment with anthracyclines within 90 days before first dose of ZW25 and/or total lifetime load exceeding 360 mg/m2 Adriamycin or equivalent
6.Use of any medications or substances that are strong inhibitors or inducers of CYP3A isoenzymes within 7 days of first dose of any study drug
14.Acute or chronic uncontrolled renal disease, pancreatitis, or severe liver disease (Child-Pugh Class C)
15.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.)
16.Major surgery ≤ 3 weeks prior to the first dose of ZW25
17.Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
18.Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures
19.Females who are breastfeeding or pregnant, and females and males planning a pregnancy
7.History of life-threatening hypersensitivity to monoclonal antibodies, XML File Identifier: 2LZ33yYQqmBiBGpwbnSiOMkiyFA= Page 34/51 recombinant proteins, or excipients in the drug formulation
20.Brain metastases: Untreated 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 subjects who are off steroids and anticonvulsants and are neurologically stable for at least 1 month at the time of screening).
21.Poorly-controlled seizures
22.History of or ongoing leptomeningeal disease (LMD). If LMD has been reported radiographically on baseline magnetic resonance imaging (MRI), but is not suspected clinically by the investigator, the patient must be free of neurological symptoms of LMD
23.Grade 3 or greater peripheral neuropathy
8.Prior treatment with palbociclib or any other CDK4/6 inhibitors, including experimental agents
10.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)
9.Use of corticosteroids administered at doses equivalent to > 15 mg per day of prednisone within 2 weeks of first ZW25 dosing unless otherwise approved by the sponsor medical monitor. Topical, ocular, intra-articular, intranasal, and/or inhalational corticosteroids are permitted.
11.QTc Fridericia (QTcF) >470 ms
13.Active hepatitis B or hepatitis C infection
14.Acute or chronic uncontrolled renal disease, pancreatitis, or severe liver disease (Child-Pugh Class C)
2.Prior treatment with chemotherapy, other anti-cancer therapy not otherwise specified, or hormonal cancer therapy ≤ 3 weeks before the first dose of ZW25

The study team makes the final eligibility decision.

Where it's taking place

United States
Canada

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States; Canada. Enter your location above to see the nearest site and check your eligibility.

Explore other conditions

Obesity Type 2 diabetes Type 1 diabetes Prediabetes Weight loss Metabolic syndrome High cholesterol High triglycerides High blood pressure PCOS Hypothyroidism Thyroid disease Gout Fatty liver disease (NAFLD/NASH)Heart failure Coronary artery disease

BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.