Mass General - Division of Clinical Research

General Inclusion Criteria: - Part A: Patient must have histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the patient - Eastern Cooperative Oncology Group Performance Status 0-1 - Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) - Fresh biopsies may be required - Negative HIV, hepatitis B, or hepatitis C test result - Women of childbearing potential and male participants must agree to remain abstinent or use contraceptive methods as defined by the protocol Additional Specific Inclusion Criteria for Participants with Melanoma: - Histologically confirmed, unresectable stage III or stage IV melanoma - Previously treated with approved anti-programmed death-ligand 1 (PD-L1)/anti-programmed death-1 (PD-1) agents with or without approved anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy and up to one additional treatment regimen Additional Specific Inclusion Criteria for Participants with Non-small Cell Lung Cancer (NSCLC) who Previously Received Treatment for Metastatic Disease: - Histologically confirmed advanced NSCLC - Previously treated with approved PD-L1/PD-1 inhibitors and platinum-based chemotherapy - Not more than 2 prior lines of treatment for metastatic disease are allowed prior to enrolling to the study - Participants must have experienced initial clinical benefit (stable disease or better) from most recent checkpoint inhibitor (CPI) therapy - Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening Additional Specific Inclusion Criteria for Participants with Non-small Cell Lung Cancer (NSCLC) who Previously Did Not Receive Treatment for Metastatic Disease: - Histologically confirmed advanced NSCLC - Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening Additional Specific Inclusion Criteria for Participants with Small Cell Lung Cancer (SCLC): - Histologically confirmed SCLC - Participants may have had prior chemotherapy, radiation therapy, or declined approved therapies for SCLC Additional Specific Inclusion Criteria for Participants with Esophageal Squamous Cell Carcinoma (ESCC): - Participants whose major lesion was histologically confirmed as squamous cell carcinoma or adenosquamous cell carcinoma of the esophagus - Patients who have previously received not more than 1 prior line of treatment for metastatic disease prior to enrolling to the study

General Exclusion Criteria: - Pregnancy, lactation, or breastfeeding - Known hypersensitivity to any of the components of RO7121661 - Active or untreated central nervous system (CNS) metastases - An active second malignancy - Evidence of concomitant diseases, metabolic dysfunction, physical examination findings, or clinical laboratory findings 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 - Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or other infection - Treatment with oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1 - Active or history of autoimmune disease or immune deficiency - Prior treatment with adoptive cell therapies, such as CAR-T therapies - Concurrent therapy with any other investigational drug <28 days or 5 half-lives of the drug, whichever is shorter, prior to the first RO7247669 administration - Regular immunosuppressive therapy - Radiotherapy within the last 4 weeks before start of study drug treatment, with the exception of limited palliative radiotherapy - Prior treatment with a T-cell immunoglobulin and mucin domain-3 (TIM-3) inhibitor Additional Specific Exclusion Criteria for Participants with NSCLC who Previously Received Treatment for Metastatic Disease: - Patients with the following mutations, rearrangements, translocations are not eligible: epidermal growth factor receptor (EGFR); anaplastic lymphoma kinase (ALK); ROS proto-oncogene 1 (ROS1), BRAFV600E, and neurotrophic receptor tyrosine kinase (NTRK) Additional Specific Exclusion Criteria for Participants with NSCLC who Did Not Previously Receive Treatment for Metastatic Disease: - Prior therapy for metastatic disease - Adjuvant anti-PD-1 or anti-PD-L1 therapy Additional Specific Exclusion Criteria for Participants with Small-Cell Lung Cancer (SCLC): - Prior therapy with any immune CPIs (such as anti-PD-L1/PD-1, CTLA-4) Additional Specific Exclusion Criteria for Participants with Esophageal Squamous Cell Carcinoma (ESCC): - Prior therapy with any immunomodulatory agents