PRIMARY OBJECTIVE:~I. Determine the proportion of activated CD8+ T cells at baseline and after treatment with atezolizumab and tiragolumab.~SECONDARY OBJECTIVES:~I. Determine the objective response rate (ORR) of patients with advanced rare cancers to the combination of atezolizumab and tiragolumab using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 and Immune-Modified (i)RECIST guidelines.~II. Measure progression-free survival (PFS) time (time frame: baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination).~III. Measure the proportion of patients with a clinically promising increase in CD8+ T cell infiltration following treatment with atezolizumab and tiragolumab.~EXPLORATORY OBJECTIVES:~I. Investigate immune activation markers and the immune composition (regulatory T [Treg], natural killer [NK], B-cells, macrophages, myeloid-derived suppressor cells [MDSC], tumor mutation burden [TMB], microsatellite instability [MSI]) in tumor microenvironment (TME) before and after study treatment.~II. Measure T cell receptor (TCR) signaling in tumor-infiltrating T cells in the TME as well as in circulating T cells in blood before and after study treatment using multiplex immunofluorescence assays (IFAs)-developed by the National Cancer Institute (NCI)-Frederick Pharmacodynamic Assay Development & Implementation Section (PADIS)-and use these measurements to evaluate the relationship between TCR signaling in circulating T cells and TME.~III. Evaluate potential associations between atezolizumab and tiragolumab activity and tumor genomic alterations, genomic expression, or TMB as determined from genomic analysis of biopsy samples.~IV. Evaluate genomic alterations in circulating tumor deoxyribonucleic acid (DNA) (ctDNA) and their potential association with therapy response or resistance.~V. Evaluate the pharmacodynamic effects of the treatment on biomarkers of cell death and epithelial-to-mesenchymal transition (EMT) in tumor tissue and circulating tumor cells (CTCs).~VI. Evaluate markers of immune response and the presence of tertiary lymphoid structures (TLS) in TME at baseline and following atezolizumab plus tiragolumab therapy.~OUTLINE:~Patients receive atezolizumab and tiragolumab intravenously (IV) on day 1 of a 21-day cycle on study. Patients also undergo echocardiography (ECHO) during screening, and computed tomography (CT) scans, tumor biopsy, and blood sample collection on study.
This phase II trial tests how well atezolizumab works in combination with tiragolumab in treating patients with rare solid tumors that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced stage). Immunotherapy with monoclonal antibodies, such as atezolizumab and tiragolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The study biopsy takes small pieces of cancer tissue from a tumor. The purpose of these biopsies is to compare the body's immune response against the tumor before and after treatment with the study drugs. Blood samples will also be collected for the study. The researchers will use the samples to learn more about how atezolizumab and tiragolumab work and which patients in the future might be most likely to respond to atezolizumab and tiragolumab. Using atezolizumab in combination with tiragolumab may help to shrink tumors in patients diagnosed with advanced stage rare solid-tumor cancers.