ZW25 in Subjects with Advanced or Metastatic HER2-Amplified Biliary Tract Cancer

Phase 1

• Conditions: Subjects with HER2-amplified, inoperable and advanced or metastatic Biliary Tract Cancer (BTC), ZW25 in Subjects with Advanced or Metastatic HER2-Amplified Biliary Tract Cancer; MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-000459-11-IT
• Lead Sponsor: Zymeworks Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-10-22
• Last Update Posted: 7 December 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1.Histologically- or cytologically-confirmed BTC, including ICC, ECC or GBC.
2.Locally advanced or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies.
3.Received at least 1 prior regimen of systemic therapy for advanced disease, including 1 gemcitabine containing regimen, and experienced disease progression after or developed intolerance to the most recent prior therapy. For subjects who have received prior adjuvant or neoadjuvant treatment, if progression has occurred <6 months from completion of the adjuvant or neoadjuvant therapy, this regimen will be considered as 1 prior line of therapy for advanced disease.
4.Subjects must have at least 1 measurable target lesion by RECIST 1.1. Subjects who have received prior local therapy (embolization, chemoembolization, radiofrequency ablation, or radiation therapy) are eligible provided measurable disease falls outside of the treatment field or is within the treatment field and has shown =20% growth in size since post-treatment assessments.
5.Subjects must test positive for HER2 amplification by in situ hybridization (ISH) assay at a central laboratory on a new biopsy or archival tissue. Note that fine needle aspirates (FNAs; cytology samples) and biopsies from sites of bone metastases are not acceptable. Testing may occur at any time after diagnosis of advanced or metastatic disease and before study enrollment.
6.Male or female, =18 years of age (or the legal age of adulthood per country-specific regulations).
7.Eastern Cooperative Oncology Group (ECOG) performance status (PS) =1.
8.Adequate hematologic function, defined as absolute neutrophil count (ANC) =1.5 x 109/L, platelet count =75 x 109/L (not requiring transfusion support), and hemoglobin (Hgb) =9 g/dL (subjects with chronic anemia that is supported by intermittent red blood cell [RBC] transfusions are eligible).
9.Liver function: serum bilirubin =1.5 x the upper limit of normal (ULN) or =3 x ULN for subjects with Gilbert's disease, aspartate aminotransferase (AST) =3 x ULN, and alanine aminotransferase (ALT) = 3 x ULN. For subjects with liver involvement, AST and ALT =5.0 x ULN is acceptable.
10.Adequate cardiac function, as defined by left ventricular ejection fraction (LVEF) =50%.
11.Kidney function: glomerular filtration rate (GFR) =30 mL/min as estimated by the Modification of Diet in Renal Disease (MDRD) equation .
12.Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (ß hCG) pregnancy test result within 3 days prior to the first dose of ZW25. Females with false positive urine test results can be enrolled if subsequent serum testing is negative.
13.For female subjects who are not surgically sterile or post-menopausal and for male subjects with a partner of child-bearing potential, willingness for the couple 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 ZW25. These include, but are not limited to, established use of oral, implanted, or injected hormonal contraceptives or placement of intra-uterine device or intra-uterine system
14.Male subjects must agree to not donate sperm and female subjects must agree to not donate oocytes starting at screening and throughout the study period, and for at least 12 months after the last dose of ZW25.
15.The subject or subject's legally acceptable representative must provide written informed consent. Subjects

Exclusion Criteria

1.Received systemic anti-cancer therapy within 3 weeks of the first dose of ZW25. Received radiotherapy within 2 weeks of the first dose of ZW25.
2.Had major surgery within 4 weeks of the first dose of ZW25.
3.Prior treatment with HER2-targeted agents.
4.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 subjects who are off steroids and anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks at the time of screening).
5.Known leptomeningeal disease (LMD). If LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the investigator, the subject must be free of neurological symptoms of LMD.
6.Concurrent uncontrolled or active hepatobiliary disorders or untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, unresolved biliary obstruction, biloma or abscess. Any complications should be resolved within 2 weeks prior to the first dose of ZW25.
7.Prior or concurrent invasive malignancy whose natural history or treatment has, in the opinion of the investigator or medical monitor, the potential to interfere with the safety or efficacy assessment of the investigational regimen.
8.Significant acute infection or chronic infections that have not stabilized with treatment.
9.Active hepatitis, including the following:
a.Acute or chronic hepatitis B (Exception: subjects who are hepatitis B surface antigen positive are eligible if they have HBV DNA less than 500 IU/mL)
b.Infection with hepatitis C (Exception: subjects who have no history of curative viral treatment and are documented to be viral load negative are eligible; subjects who have completed curative viral therapy =12 weeks prior to enrollment, and viral load is negative are eligible)
10.Infection with HIV-1 or HIV-2 (Exception: subjects with well-controlled HIV [e.g., CD4 >350/mm3 and undetectable viral load] are eligible).
11.Females who are breastfeeding or pregnant, and females and males planning a pregnancy.
12.History of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of ZW25.
13.Treatment with anthracyclines within 90 days before first dose of ZW25 and/or total lifetime load exceeding 360 mg/m2 Adriamycin® or equivalent.
14.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 medical monitor. Topical, ocular, intraarticular, intranasal, and/or inhalational corticosteroids are permitted.
15.Ongoing, clinically significant toxicity (Grade 2 or higher) associated with prior cancer therapies, with the following exceptions:
a.Alopecia
b.Congestive heart failure (CHF), which must have been = Grade 1 at the time of occurrence and which must have completely resolved
16.QTc Fridericia (QTcF) >470 ms.
17.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 CHF.
18.Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease.
19.Any

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified