HER2-amplified Biliary Tract Cancers Clinical Trial
— HERIZON-BTC-01Official title:
A Phase 2b, Open-label, Single-arm Study of ZW25 Monotherapy in Subjects With Advanced or Metastatic HER2-amplified Biliary Tract Cancers
| Verified date | May 2024 |
| Source | Jazz Pharmaceuticals |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This multicenter, open-label, single-arm trial will evaluate the anti-tumor activity of ZW25 (zanidatamab) monotherapy in subjects with human epidermal growth factor receptor 2 (HER2)-amplified, inoperable and advanced or metastatic biliary tract cancer (BTC), including intra-hepatic cholangiocarcinoma (ICC), extra-hepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC).
| Status | Active, not recruiting |
| Enrollment | 87 |
| Est. completion date | October 31, 2024 |
| Est. primary completion date | July 28, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Histologically- or cytologically-confirmed BTC, including ICC, ECC or GBC. - Locally advanced or metastatic BTC and not eligible for curative resection, transplantation, or ablative therapies. - Received at least 1 prior gemcitabine-containing systemic chemotherapy regimen for advanced disease, and experienced disease progression after or developed intolerance to the most recent prior therapy. For subjects who received gemcitabine in prior adjuvant or neoadjuvant treatment, if progression occurred < 6 months from the latter of primary surgical resection or completion of gemcitabine-containing adjuvant therapy, they will be considered as having received 1 prior line of therapy for advanced disease. - Subjects must test positive for HER2 amplification by 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. - Male or female, =18 years of age (or the legal age of adulthood per country-specific regulations). - Eastern Cooperative Oncology Group (ECOG) performance status = 1. - Adequate organ function. - Adequate cardiac function, as defined by left ventricular ejection fraction = 50%. Exclusion Criteria: - 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. - Prior treatment with HER2-targeted agents. - 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). - 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. - 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, infected biloma or abscess. Any complications must be resolved more than 2 weeks prior to the first dose of ZW25. - Prior or concurrent 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. - Active hepatitis - Infection with human immunodeficiency virus (HIV)-1 or HIV-2 - QTc Fridericia (QTcF) > 470 ms. - History of myocardial infarction or unstable angina within 6 months prior to enrollment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease. - Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease. |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Princess Margaret Hospital | Toronto | Ontario |
| Chile | Centro de Cáncer Nuestra Señora de la Esperanza | Santiago | |
| Chile | Radiomed (Clinica Alemana de Temuco) | Temuco | |
| China | Beijing Cancer Hospital | Beijing | |
| China | Peking Union Medical College Hospital | Beijing | |
| China | Jilin Cancer Hospital | Changchun | |
| China | Hunan Cancer Hospital | Changsha | |
| China | West China Hospital | Chengdu | |
| China | The First Affiliated Hospital, Sun Yat-sen University | Guangzhou | |
| China | Sir Run Run Shaw Hospital, Zhejiang University School of Medicine | Hangzhou | |
| China | The First Affiliated Hospital of Zhejiang University | Hangzhou | |
| China | Zhejiang Cancer Hospital | Hangzhou | |
| China | Zhejiang Provincial People's Hospital | Hangzhou | |
| China | Affiliated Tumor Hospital of Harbin Medical University | Harbin | |
| China | Anhui Provincial Hospital | Hefei | |
| China | Huzhou Central Hospital | Huzhou | |
| China | Jinhua Central Hospital | Jinhua | |
| China | The First Hospital Of Lanzhou University | Lanzhou | |
| China | Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School | Nanjing | |
| China | Shandong Provincial Third Hospital | Shandong | |
| China | Affiliated Zhongshan Hospital of Fudan University | Shanghai | |
| China | The Third Affiliated Hospital of the Chinese PLA | Shanghai | |
| China | Tianjin Medical University Cancer Institute and Hospital | Tianjin | |
| China | Weifang People's Hospital | Weifang | |
| China | Hubei Cancer Hospital | Wuhan | |
| China | The First Affiliated Hospital of Zhengzhou University | Zhengzhou | |
| France | Oncologie médicale Hopital Jean Minjoz | Besançon | |
| France | Institut de Cancerologie et d'Hematologie Hopital Morvan - CHRU de Brest | Brest | |
| France | Hopitaux de La Timone | Marseille | |
| France | Département Oncologie Gastro-entérologie CHRU de Poitiers La Miletrie | Poitiers | |
| France | Département De Médecine | Villejuif | |
| Italy | Fondazione del Piemonte per l'Oncologia (IRCCS) | Candiolo | |
| Italy | Istituto Clinico Humanitas | Milan | |
| Italy | Istituto Nazionale Dei Tumori | Milano | |
| Italy | Istituto Oncologico Veneto - I.R.C.C.S. | Padova | |
| Korea, Republic of | Gyeongsang National University Hospital | Jinju-si | |
| Korea, Republic of | Pusan National University Hospital | Pusan | |
| Korea, Republic of | Seoul National University Bundang Hospital | Seongnam | |
| Korea, Republic of | Asan Medical Center Hospital | Seoul | |
| Korea, Republic of | Samsung Medical Center | Seoul | |
| Korea, Republic of | Seoul National University Hospital | Seoul | |
| Korea, Republic of | Severance Hospital Yonsei University Health System | Seoul | |
| Korea, Republic of | The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | |
| Spain | Hospital Universitario Vall d'Hebron | Barcelona | |
| Spain | Universitario Germans Trias i Pujol | Barcelona | |
| Spain | Hospital Universitario Reina Sofia | Cordoba | |
| Spain | Hospital General Universitario Gregorio Marañón | Madrid | |
| Spain | Hospital Universitario Doce de Octubre | Madrid | |
| Spain | Corporacio Sanitaria Parc Tauli | Sabadell | |
| Spain | Hospital Miguel Servet | Zaragoza | |
| United Kingdom | Imperial College Healthcare NHS Trust | London | |
| United Kingdom | Royal Free London NHS Foundation Trust | London | |
| United Kingdom | University College London Hospitals (UCLH) | London | |
| United States | Winship Cancer Institute, Emory University | Atlanta | Georgia |
| United States | University of Maryland Greenebaum Cancer Center | Baltimore | Maryland |
| United States | University of Texas Southwestern Medical Center - Hospital | Dallas | Texas |
| United States | City of Hope National Medical Center | Duarte | California |
| United States | Banner MD Anderson Cancer Center | Gilbert | Arizona |
| United States | University of Texas MD Anderson Cancer Center | Houston | Texas |
| United States | Memorial Sloan Kettering Cancer Center | New York | New York |
| United States | Advent Health Cancer Institute | Orlando | Florida |
| United States | Oregon Health and Science University | Portland | Oregon |
| United States | Washington University School of Medicine | Saint Louis | Missouri |
| United States | University of California Los Angeles | Santa Monica | California |
| United States | Seattle Cancer Care Alliance | Seattle | Washington |
| United States | University of Arizona Cancer Center | Tucson | Arizona |
| United States | The Oncology Institute of Hope and Innovation | Whittier | California |
| Lead Sponsor | Collaborator |
|---|---|
| Jazz Pharmaceuticals | BeiGene, Ltd. |
United States, Canada, Chile, China, France, Italy, Korea, Republic of, Spain, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Confirmed objective response rate (ORR) by independent central review (ICR) | Number of subjects who achieved a confirmed best overall response (BOR) of either complete response (CR) or partial response (PR) during treatment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | Up to 2.5 years | |
| Secondary | Duration of response (DOR) by ICR | The time from the first objective response (CR or PR) to documented progressive disease (PD) per RECIST 1.1, clinical progression, or death from any cause | Up to 2.5 years | |
| Secondary | DOR at = 16 weeks by ICR | Proportion of subjects with a DOR = 16 weeks per RECIST 1.1 | 24 weeks to 2.5 years | |
| Secondary | Disease control rate (DCR) by ICR | Number of subjects who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1 | Up to 2.5 years | |
| Secondary | Progression-free survival (PFS) by ICR | The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause | Up to 2.5 years | |
| Secondary | ORR by investigator assessment | Number of subjects who achieved a BOR of either CR or PR during treatment per RECIST 1.1 | Up to 2.5 years | |
| Secondary | DOR by investigator assessment | The time from the first objective response (CR or PR) to documented PD per RECIST 1.1, clinical progression, or death from any cause | Up to 2.5 years | |
| Secondary | DOR at = 16 weeks by investigator assessment | Proportion of subjects with a DOR = 16 weeks per RECIST 1.1 | 24 weeks to 2.5 years | |
| Secondary | DCR by investigator assessment | Number of subjects who achieved a best response of CR, PR, or SD during treatment per RECIST 1.1 | Up to 2.5 years | |
| Secondary | PFS by investigator assessment | The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause | Up to 2.5 years | |
| Secondary | Overall survival | The time from the first dose of study treatment until the date of death from any cause | Up to 2.5 years | |
| Secondary | Incidence of adverse events (AEs) | Number of subjects who experienced AEs or serious adverse events | Up to 2.5 years | |
| Secondary | Incidence of laboratory abnormalities | Number of subjects who experienced a maximum severity of Grade 3 or higher post-baseline laboratory 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 2.5 years | |
| Secondary | Maximum serum concentration of ZW25 | Up to 2.5 years | ||
| Secondary | Trough concentration of ZW25 | Minimum observed serum concentration (trough) | Up to 2.5 years | |
| Secondary | Incidence of anti-drug antibodies (ADAs) | Number of subjects who develop ADAs | Up to 2.5 years |