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A Safety and Efficacy Study of ZW25 (Zanidatamab) Plus Combination Chemotherapy in HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer

Trial Status: Active

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).

Inclusion Criteria

  • 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)

California

Los Angeles
Los Angeles County-USC Medical Center
Status: APPROVED
Contact: Charlean Ketchens
Phone: 323-865-3035
USC / Norris Comprehensive Cancer Center
Status: ACTIVE
Contact: Charlean Ketchens
Phone: 323-865-3035
Newport Beach
Hoag Memorial Hospital
Status: ACTIVE
Contact: Leila D. Andres
Phone: 949-764-8092

Florida

Tampa
Moffitt Cancer Center
Status: ACTIVE

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE

Pennsylvania

Philadelphia
Fox Chase Cancer Center
Status: ACTIVE
Contact: systems coordinator

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE
Contact: Alma DeLaGarza
Phone: 713-792-2073

Part 1 of the study will first evaluate the safety and tolerability of ZW25 plus standard

first-line combination chemotherapy (XELOX, FP, or mFOLFOX6 for GEA; mFOLFOX6 with or without

bevacizumab for CRC; and CisGem for BTC) and will confirm the recommended dosage (RD) of ZW25

when administered in combination with each of these multi-agent chemotherapy regimens. Then,

Part 2 of the study will evaluate the anti-tumor activity of ZW25 plus combination

chemotherapy in HER2-expressing GEA, BTC, and CRC.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Zymeworks Inc.

  • Primary ID ZWI-ZW25-201
  • Secondary IDs NCI-2019-03042
  • Clinicaltrials.gov ID NCT03929666