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

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)