A Study of Lomvastomig (RO7121661) and Tobemstomig (RO7247669) Compared With Nivolumab in Participants With Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus

Exclusion Criteria

• •Pregnancy, lactation, or breastfeeding
• •Known hypersensitivity to any of the components of RO7121661, RO7247669, or nivolumab, including but not limited to, hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
• •Patients with significant malnutrition. Patients whose nutrition has been well controlled for ≥28 days prior to randomization may be enrolled
• •Evidence of complete esophageal obstruction not amenable to treatment
• •Higher risk of bleeding or fistula caused by esophageal lesions invading adjacent organs (aorta or tracheobronchial tree). Patients with manageable fistula may be included at the Investigator's discretion.
• •Symptomatic central nervous system (CNS) metastases
• •Spinal cord compression not definitively treated with surgery and/or radiation or without evidence that disease has been clinically stable for ≥14 days prior to randomization
• •Active or history of carcinomatous meningitis/leptomeningeal disease
• •Asymptomatic CNS primary tumors or metastases if they have requirement for steroids or enzyme inducing anticonvulsants in the last 28 days prior to randomization
• •Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry
• •Active second malignancy (with some exceptions)
• •Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, known autoimmune diseases or immune deficiency, or other diseases with ongoing fibrosis (such as scleroderma, pulmonary fibrosis, emphysema, neurofibromatosis, palmar/plantar fibromatosis, etc.).
• •Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
• •Significant cardiovascular/cerebrovascular disease within 6 months prior to randomization
• •Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis \[TB\] and typical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 28 days prior to randomization
• •Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease.
• •Major surgical procedure or significant traumatic injury (excluding biopsies) within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study
• •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications
• •Dementia or altered mental status that would prohibit informed consent
• •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (expected to occur once monthly or more frequently)
• •Active or history of autoimmune disease or immune deficiency
• •Positive human immunodeficiency virus (HIV) test at screening
• •Positive hepatitis B surface antigen (HBsAg) or positive total hepatitis B core antibody (HBcAb) test at screening
• •Positive hepatitis C virus (HCV) antibody test at screening
• •Prior cancer therapy with any immunomodulatory agents including checkpoint inhibitors (CPIs; such as anti-PDL1/PD1, anti-CTLA-4, anti-LAG3, anti-TIM3)
• •Vaccination with live vaccines within 28 days prior to randomization, or anticipation that a live attenuated vaccine will be required during the study
• •Treatment with therapeutic oral or IV antibiotics within 14 days prior to randomization
• •Concurrent therapy with any other investigational drug (defined as treatment for which there is currently no regulatory authority approved indication) 28 days or 5 half-lives of the drug (whichever is shorter) prior to randomization
• •Treatment with immune-modulating and immune suppressive agents/medication 5 half-lives or 28 days (whichever is shorter) prior to randomization
• •Regular immunosuppressive therapy (i.e., for organ transplantation, chronic rheumatologic disease)
• •Radiotherapy within the last 28 days before start of study drug treatment is not allowed, with the exception of limited palliative radiotherapy
• •Prior treatment with adoptive cell therapies, such as chimeric antigen receptor T cells (CAR-T) therapies