PRIMARY OBJECTIVE:~I. Determine the overall response rate (by Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1) for selinexor in combination with atezolizumab in immune checkpoint inhibitor (ICI)-naive patients with alveolar soft part sarcoma (ASPS).~SECONDARY OBJECTIVE:~I. Assess the number of activated CD8+ T cells infiltrating the tumor before and after atezolizumab + selinexor combination treatment, and correlate treatment-induced changes with clinical response.~EXPLORATORY OBJECTIVES:~I. Compare RECIST v 1.1 versus (vs) immune RECIST (iRECIST) in patients with ASPS on atezolizumab + selinexor.~II. Examine changes in PD-1/PD-L1 expression in the tumor microenvironment before and after atezolizumab + selinexor treatment, and correlate treatment-induced changes with clinical response.~III. Evaluate potential associations between atezolizumab + selinexor activity and tumor genomic alterations.~OUTLINE: This is a randomized phase 2 trial that incorporates a safety run-in of the selinexor in combination with atexolizumab. After the safety run-in phase, patients are randomized to 1 of 2 arms. Patients with advanced soft tissue sarcoma are assigned to Arm I.~ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 8 of cycle 1, and then on day 1 of subsequent cycles. Patients also receive selinexor orally (PO) once weekly (QW) on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy at baseline, cycle 1 day 8 and cycle 3 day 1, computed tomography (CT) and magnetic resonance imaging (MRI) at baseline, end of cycle 2, and every 2 cycles thereafter, magnetic resonance imaging (MRI), and collection of blood samples at baseline, at disease re-staging and at time of disease progression.~ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 8 of cycle 1, and then on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm I. Patients also undergo biopsy at baseline and cycle 1 day 8, CT and MRI at baseline, end of cycle 2, and every 2 cycles thereafter, and collection of blood samples at baseline, at disease re-staging and at time of disease progression.~After completion of study treatment, participants are followed up for 30 days.
This phase II trial tests whether atezolizumab alone or in combination with selinexor works to shrink tumors in patients with alveolar soft part sarcoma and whether the study drugs are better than the usual approach in treating this type of cancer. The usual approach is defined as care most people get for alveolar soft part sarcoma if they are not part of a clinical study, which includes treatment with radiation, kinase inhibitor drugs, immunotherapy drugs, or chemotherapy drugs. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by blocking a protein called CRM1, which may help keep cancer cells from growing and may kill them. Giving atezolizumab alone or in combination with selinexor may help shrink tumors and stabilize the cancer in patients with alveolar soft part sarcoma.