HER2+/HR+ Breast Cancer Clinical Trial
Official title:
Phase 2a Study of ZW25 in Combination With Palbociclib Plus Fulvestrant
| Verified date | December 2023 |
| Source | Jazz Pharmaceuticals |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 51 |
| Est. completion date | October 26, 2025 |
| Est. primary completion date | April 28, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - 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 Exclusion Criteria: - 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 - 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 |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Tom Baker Cancer Centre | Calgary | Alberta |
| Canada | Jewish General Hospital | Montreal | Quebec |
| Canada | The Ottawa Hospital Cancer Centre | Ottawa | Ontario |
| Canada | Sunnybrook Research Institute | Toronto | Ontario |
| Spain | Hospital Universitario Vall d'Hebrón | Barcelona | |
| Spain | Hospital General Universitario de Elche | Elche | Alicante |
| Spain | Hospital Ruber Internacional | Madrid | |
| Spain | Hospital Universitario Virgen de la Victoria | Málaga | |
| Spain | Hospital Universitario Virgen del Rocío | Sevilla | |
| Spain | Hospital Clínico Universitario de Valencia | Valencia | |
| United States | Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | UCLA Hematology/Oncology Parkside | Santa Monica | California |
| United States | Seattle Cancer Care Alliance | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| Jazz Pharmaceuticals |
United States, Canada, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Incidence of dose-limiting toxicities (DLTs; Part 1) | Number of participants who experienced a DLT. DLTs include specifically defined adverse events (AEs) considered to be related to ZW25, including combination of ZW25 with palbociclib and/or fulvestrant | Up to 4 weeks | |
| Primary | Incidence of AEs (Part 1) | Number of participants who experienced AEs, serious adverse events (SAEs), or adverse events of special interest (AESIs) | Up to 3.5 years | |
| Primary | Incidence of lab abnormalities (Part 1) | Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline lab abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. | Up to 3.5 years | |
| Primary | Progression-free survival 6 (PFS6; Part 2) | Percent of modified intent to treat patients with PFS greater than or equal to 24 weeks | Up to 6 months | |
| Secondary | Maximum serum concentration of ZW25 (Parts 1 and 2) | Up to 9 months | ||
| Secondary | Trough concentration of ZW25 (Parts 1 and 2) | Minimum observed serum concentration (trough) | Up to 9 months | |
| Secondary | Incidence of anti-drug antibodies (ADAs) (Parts 1 and 2) | Number of participants who develop ADAs | Up to 10 months | |
| Secondary | Objective response rate (Part 2) | Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and as assessed by the investigator | Up to 3.5 years | |
| Secondary | Duration of response (Part 2) | Time from the first objective response (CR or PR) to documented progressive disease per RECIST 1.1 or death within 30 days of last dose of study drug (ZW25, palbociclib, and/or fulvestrant) from any cause | Up to 3.5 years | |
| Secondary | Disease control rate (Part 2) | Number of participants who achieved a best response of CR, PR, or stable disease during treatment according to the RECIST version 1.1 and as assessed by the investigator | Up to 3.5 years | |
| Secondary | Progression-free survival (PFS; Part 2) | Time from the first dose of ZW25, palbociclib, and/or fulvestrant to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause | Up to 3.5 years | |
| Secondary | Overall survival (Part 2) | Time from the first dose of ZW25, palbociclib, and/or fulvestrant until death from any cause | Up to 3.5 years | |
| Secondary | Incidence of AEs (Part 2) | Number of participants who experienced AEs, SAEs, or AESIs | Up to 3.5 years | |
| Secondary | Incidence of lab abnormalities (Part 2) | Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline lab abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's CTCAE, version 5.0. | Up to 3.5 years |