Inclusion Criteria:

          -  Major lesion was histologically confirmed esophageal squamous-cell carcinoma (ESCC)

          -  Patients who have previously received 1 line of treatment with either a
             fluoropyrimidine- and platinum- or a taxane- and platinum-based regimen in
             non-curative intention prior to randomization; or patients who received treatment with
             a fluoropyrimidine-/taxane- and platinum-based regimen in curative intention and had
             recurrence within 24 weeks after the last dose of the treatment

          -  Radiologically measurable disease according to RECIST v1.1. Previously irradiated
             lesions should not be counted as target lesions unless clearly progressed after the
             radiotherapy

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          -  A life expectancy of at least (≥)12 weeks

          -  Tissue samples must be provided for analysis of anti-programmed death ligand-1 (PD-L1)
             tumor positivity

          -  Adverse events from any prior radiotherapy, chemotherapy, or surgical procedure must
             have resolved to Grade ≤1, except alopecia (any grade), vitiligo, endocrinopathy
             managed with replacement therapy, and Grade 2 peripheral neuropathy

          -  Adequate cardiovascular, hematological, liver, and renal function

          -  Serum albumin ≥25 grams per liter (g/L),

          -  For participants not receiving therapeutic anticoagulation: prothrombin time (PT) and
             activated partial thromboplastin time ≤1.5 times (×) the upper limit of normal (ULN);
             for participants receiving therapeutic anticoagulation: stable anticoagulant regimen

          -  A female participant is eligible to participate if she is not pregnant, not
             breastfeeding, not a woman of childbearing potential (WOCBP), or a WOCBP who agrees to
             remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods
             during the treatment period and for at least 5 months after the final dose of study
             drug and have a negative pregnancy test (blood) within the 7 days prior to
             randomization.

          -  A male participant must remain abstinent (refrain from heterosexual intercourse) or
             use contraceptive measures such as a condom plus an additional contraceptive method
             and refrain from donating sperm during the treatment period and for at least 5 months
             after the final dose of study drug

        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)

          -  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