A Study of IMU-131 (HER-Vaxx) in Combination With Chemotherapy or Pembrolizumab in Patients With Metastatic HER2/Neu Over-Expressing Gastric Cancer (nextHERIZON)

Who can take part

• Age ≥ 18 years with confirmed diagnosis of advanced or metastatic HER2/neu overexpressing gastric or GEJ adenocarcinoma
• Progressed on or after trastuzumab therapy
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy of a minimum of 3 months
• At least one measurable lesion as defined by RECIST 1.1 criteria and assessed by the local investigator
• HER2/neu overexpression assessed using post-progression fresh or archival tissue, or post-progression pathology report
• Adequate left ventricular ejection function at baseline, defined as left ventricular ejection fraction (LVEF) > 50% by echocardiogram or Multi Gated Acquisition (MUGA) scan
• Adequate hematologic, liver and renal function
• A female patient of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 120 days after the last dose of assigned treatment

Who cannot take part

• Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin
• Systemic chemotherapy or major surgery within 28 days before starting study treatment and recovered from all adverse events ≤ Grade 1 or baseline with possible exceptions for neuropathy and endocrine-related AEs
• Received prior radiotherapy within 2 weeks of start of study treatment and recovered from all radiation-related toxicities and not require corticosteroids; or history of radiation pneumonitis
• Previous treatment with trastuzumab-deruxtecan or any other anti-HER2 therapy (except trastuzumab)
• Prior organ transplantation, including allogenic stem-cell transplantation
• Chronic immunosuppressive therapy within 7 days prior the first dose of study drug
• Current participation or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
• Any vaccination within 30 days prior to starting study treatment
• Arm 2 only: Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Arm 2 only: Has received prior therapy with an ICI or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from treatment due to a grade 3 or higher adverse event
• Previous malignant disease (other than primary malignancy) within the last 5 years, except basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
• Clinically significant cardiovascular disease, or other diseases that in the Investigator's opinion may influence the patient's tolerance to study treatment
• Active, known, or suspected autoimmune disease
• History of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
• Positivity for human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or active hepatitis B (HBsAg reactive) or active hepatitis C (HCV ribonucleic acid [RNA] qualitative) infection
• Pleural effusion or ascites requiring more than weekly drainage
• Pregnant or lactating females