Comparing Zanidatamab with Zolbetuximab for gastroesophageal adenocarcinoma

Exclusion

• −Formalin-fixed, paraffin-embedded (FFPE) tumor sample tested at a central laboratory confirming HER2-positive status.
• −HIV with CD4 \<350, active hepatitis B or C.
• −in the sub-protocolProtocolThe detailed plan a study must follow.Read more → for the treatment for which they will be later assigned
• −Additional inclusion criteriaInclusion criteriaThe things you must have or be for a study to consider you.Read more → for all sub-studies:
• −FFPE tumor sample tested at a central laboratory confirming PD-L1 Tumor Area Positivity (TAP) score ≥1%.
• −Additional inclusion criteria specific to HER2 sub-study:
• −Left ventricular ejection fraction (LVEF) ≥50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA).
• −Exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more →:
• −Unresectable disease, peritoneal dissemination, and/or positive cytology on laparoscopy.
• −Peripheral neuropathy ≥ Grade 2.
• −Active infection.
• −Chronic growth factor support for white blood cells or granulocytes.
• −≤14 days prior).
• −Local/systemic therapy for current gastroesophageal diagnosis (except one FLOX/ mFOLFOX6 dose during screeningScreeningThe checks done before joining, to see whether a study fits.Read more →).
• −Significant medical conditions compromising safety or protocol compliance.
• −Preexisting cardiac conditions.
• −Stroke, transient ischemic attack (TIA), or myocardial infarction within 6 months.
• −Prior checkpoint inhibitor therapy (anti-PD-1/PD- L1/PD-L2).
• −Malabsorption syndrome or inability to swallow oral medication.
• −History of stem cell or organ transplant.
• −Other malignancy within 3 years (exceptions: basal/squamous cell carcinoma, in situ malignancy, low-risk prostate cancer).
• −Systemic corticosteroids \>10 mg prednisone/ day or immunosuppressive therapy ≤14 days prior (exceptions: adrenal replacement, topical/ inhaled, short prophylactic courses).
• −Active or relapsing autoimmune disease (exceptions: controlled type I diabetes, hypothyroidism on replacement, controlled celiac disease, mild skin disease, other non- recurrent diseases).
• −Additional exclusion criteria for all sub-studies:
• −Poorly controlled seizures
• −Clinically significant bleeding (CTCAE ≥ Grade 3) from the gastrointestinal (GI) tract within 4 weeks prior to enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →.
• −Administered a live vaccine ≤ 4 weeks prior to enrollment
• −History of interstitial lung disease or non-infectious pneumonitis, or with severe dyspnea at rest or requiring supplementary oxygen therapy.
• −Treated with another investigational product within 28 days of enrolment.
• −Exclusion criteria specific to HER2 sub-study:
• −Total lifetime anthracycline load exceeding 360 mg/m² of doxorubicin or equivalent
• −QTc Fridericia (QTcF) \>470 ms. Note: For subjects with longer QTcF on initial electrocardiogram (ECG), follow-upFollow-upContinued check-ins after the treatment part is finished.Read more → ECG may be performed in triplicate to determine eligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more → (e.g., after correction of electrolyte abnormalities, or discontinuation of QT-prolonging drugs).
• −Ongoing Grade 2 or greater diarrhea
• −Pregnant or nursing women
• −Histologically confirmed diagnosis of resectable (i.e., radical surgery eligible), HER2-positive (defined as 3+ HER2 expression by IHC or 2+ HER2 expression by immunohistochemistry (IHC) with in situ hybridization (ISH)-positivity per central assessment) adenocarcinoma of the stomach or esophagus, including the gastroesophageal junction.
• −Concurrent anti-cancer therapy (exceptions: supportive care medications ≥1 month prior, low molecular weight heparin, prior adjuvant hormonal therapy \>3 years, palliative radiation
• −Prior FGFR-targeted therapy.
• −Prior HER2-targeted therapy (except \>5 years prior for breast cancer).
• −Conditions preventing safe surgery/biopsy.
• −Major surgery within 14 days.
• −History of hypersensitivity or contraindications to any active substance/active ingredient of any study medication, including chemotherapy components monoclonal antibodies, recombinant proteins, and/or any of the excipients listed in the ingredients of any drug formulation