HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer Clinical Trial
Official title:
Phase 2 Study of ZW25 Plus First-line Combination Chemotherapy in HER2-Expressing Gastrointestinal (GI) Cancers, Including Gastroesophageal Adenocarcinoma (GEA), Biliary Tract Cancer (BTC), and Colorectal Cancer (CRC)
| Verified date | June 2024 |
| Source | Jazz Pharmaceuticals |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is a multicenter, global, Phase 2, open-label, 2-part, first-line study to investigate the safety, tolerability, and anti-tumor activity of ZW25 (zanidatamab) plus standard first-line combination chemotherapy regimens for selected gastrointestinal (GI) cancers. Eligible patients include those with unresectable, locally advanced, recurrent or metastatic HER2-expressing gastroesophageal adenocarcinoma (GEA), biliary tract cancer (BTC), or colorectal cancer (CRC).
| Status | Active, not recruiting |
| Enrollment | 74 |
| Est. completion date | October 30, 2026 |
| Est. primary completion date | November 28, 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion: - Disease diagnosis: - Part 1: - GEA: Unresectable, locally advanced, recurrent or metastatic HER2-expressing GEA (IHC 3+ or 2+ with or without gene amplification based upon local assessment or central assessment) - BTC: Unresectable, locally advanced, recurrent or metastatic HER2-expressing BTC (including intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], or gallbladder cancer [GBC]) (IHC 3+ with or without gene amplification; or IHC 0, 1+ or 2+ with gene amplification, based upon central assessment) - CRC: Unresectable, locally advanced, recurrent or metastatic HER2-expressing CRC (IHC 3+ with or without gene amplification; or IHC 0, 1+ or 2+ with gene amplification, based upon central assessment). Patients will be required to be extended RAS (KRAS and NRAS) and BRAF wild-type based upon central assessment. - Part 2: - GEA: Unresectable, locally advanced, recurrent or metastatic HER2-expressing GEA (IHC 3+, or IHC 2+ and FISH+ by central assessment) - BTC: Same as Part 1 - CRC: Same as Part 1 - Tumor measurements as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1: - Part 1: Measurable or non-measurable disease - Part 2: Measurable disease - An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 - Adequate organ function - Adequate cardiac left ventricular function, as defined by a LVEF >/= institutional standard of normal Exclusion: - Prior treatment with a HER2-targeted agent - Prior systemic anti-cancer therapy (including investigational products) except prior adjuvant/neoadjuvant therapy, which must be completed at least 6 months prior to first study treatment dosing. For subjects with BTC and CRC the following additional exceptions apply: - BTC: patients may have started therapy for advanced disease but may not have received more than one cycle of any standard gemcitabine-based chemotherapy regimen. - CRC: patients may have started therapy for advanced disease but may not have received more than one cycle of 5-FU-based chemotherapy (< 1 month of therapy). - Patients with certain contraindications to bevacizumab cannot be enrolled on the mFOLFOX6-2 with bevacizumab arm. - Palliative radiotherapy is allowed if completed at least 2 weeks prior to first study treatment dosing - Untreated known brain metastases (patients with treated brain metastases who are off steroids, off antiseizure medications, and stable for at least 1 month at the time of screening are eligible) - Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF). Patients with known myocardial infarction or unstable angina within 6 months prior to randomization are also excluded. - QTc Fridericia (QTcF) > 470 ms. For patients with longer QTcF on initial electrocardiogram (ECG), follow-up ECG may be performed in triplicate to determine eligibility - Peripheral neuropathy > Grade 1 per NCI-CTCAE v5.0 - Clinically significant interstitial lung disease - Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen - Active hepatitis B or hepatitis C infection or infection with Human Immunodeficiency Virus (HIV)-1 or HIV-2 (Exception: patients with well controlled HIV [e.g., CD4 > 350/mm3 and undetectable viral load] are eligible) |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Princess Margaret Cancer Center | Toronto | Ontario |
| Chile | CECIM Biocinetic | Santiago | |
| Chile | Centro de Estudios Clinicos SAGA SpA | Santiago | |
| Chile | Icegclinic Research & Care | Santiago | |
| Chile | Meditek Ltda | Santiago | |
| Korea, Republic of | Pusan National University | Busan | |
| Korea, Republic of | Seoul National University Bundang Hospital | Seongnam-si | Gyeonggi-do |
| Korea, Republic of | Asan Medical Center | Seoul | |
| Korea, Republic of | Korea University Anam Hospital | Seoul | |
| Korea, Republic of | Seoul National University Hospital | Seoul | |
| Korea, Republic of | Severance Hospital | Seoul | |
| United States | University of Chicago | Chicago | Illinois |
| United States | MD Anderson Cancer Center | Houston | Texas |
| United States | Cancer and Hematology Centers of Western Michigan | Kalamazoo | Michigan |
| United States | USC/Norris Comprehensive Cancer Center | Los Angeles | California |
| United States | Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | Memorial Sloan Kettering Cancer Center | New York | New York |
| United States | Nebraska Methodist Hospital | Omaha | Nebraska |
| United States | Fox Chase Cancer Center | Philadelphia | Pennsylvania |
| United States | Virginia Mason Medical Center | Seattle | Washington |
| United States | H. Lee Moffitt Cancer Center | Tampa | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Jazz Pharmaceuticals |
United States, Canada, Chile, Korea, Republic of,
| 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 adverse events considered to be related to study treatment, including the evaluated dose level of ZW25, any component or combination of the components of a chemotherapy regimen, or the combination of ZW25 plus a chemotherapy regimen. | Up to 6 weeks | |
| Primary | Incidence of adverse events (Part 1) | Number of participants who experienced an adverse event | Up to 11 months | |
| Primary | Incidence of lab abnormalities (Part 1) | Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. | Up to 11 months | |
| Primary | Objective response rate (ORR) (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 | Up to 10 months | |
| Secondary | Objective response rate (ORR) (Part 1) | Number of participants who achieved a best response of either CR or PR during treatment per RECIST 1.1 | Up to 10 months | |
| Secondary | Disease control rate (Parts 1 and 2) | Number of participants who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1 | Up to 10 months | |
| Secondary | Duration of response (Parts 1 and 2) | Median duration of response (in months) and range (minimum, maximum) | Up to 2 years | |
| Secondary | Clinical benefit rate (Parts 1 and 2) | Number of participants with SD for = 24 weeks or a confirmed, best overall response of CR or PR per RECIST 1.1 | Up to 2 years | |
| Secondary | Progression-free survival (Parts 1 and 2) | Median progression-free survival (in months) and range (minimum, maximum) | Up to 2 years | |
| Secondary | Overall survival (Parts 1 and 2) | Median overall survival (in months) and range (minimum, maximum) | Up to 2 years | |
| Secondary | Incidence of anti-drug antibodies (ADAs) (Parts 1 and 2) | Number of participants who develop ADAs | Up to 11 months | |
| Secondary | End of infusion concentration of ZW25 (Parts 1 and 2) | Up to 11 months | ||
| Secondary | Maximum serum concentration of ZW25 (Parts 1 and 2) | Up to 11 months | ||
| Secondary | Trough concentration of ZW25 (Parts 1 and 2) | Up to 11 months | ||
| Secondary | Incidence of adverse events (Part 2) | Number of participants who experienced an adverse event | Up to 11 months | |
| Secondary | Incidence of lab abnormalities (Part 2) | Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's CTCAE, version 5.0. | Up to 11 months |