Background: Sarcomatoid mesothelioma is the most aggressive form of pleural mesothelioma and is associated with the worst prognosis of the histologic variants of this disease. In the Checkmate 743 clinical trial the patients with sarcomatoid mesothelioma who received ipilimumab and nivolumab had survival outcomes that were similar to those of patients with epithelioid mesothelioma. In comparison, the patients with sarcomatoid mesothelioma who received chemotherapy had the worst outcomes in this trial, highlighting the known limited efficacy of chemotherapy against this histologic variant. Checkmate 743 demonstrated that ipilimumab and nivolumab is a new standard of care for non-epithelioid mesothelioma. Surgery typically has not been offered to this group of patients given their historically poor outcomes. With the significant survival gains seen patients with sarcomatoid mesothelioma treated with immunotherapy, we hypothesized that surgery may extend the benefits seen with immunotherapy. Methods: Alliance for Clinical Trials in Oncology A082101 is a prospective, phase 2 nonrandomized clinical trial for patients with sarcomatoid mesothelioma. The co-primary objectives are to determine the percentage of patients with potentially resectable sarcomatoid mesothelioma able to proceed with surgery after neoadjuvant ipilimumab and nivolumab, and the progression-free survival (PFS) at 12 months (12-month PFS). For sample size determination, we assumed that if the true rate of surgery is 75% or greater, it would indicate that neoadjuvant immunotherapy is feasible to be given prior to surgery. On the other hand, if the true rate of surgery is 50% or less it would indicate that neoadjuvant immunotherapy is not worthy of further investigation. Twenty-six (26) eligible patients will be needed to receive neoadjuvant immunotherapy. If 16 or fewer of the 26 eligible patients proceed to surgery, it will be concluded that the experimental therapy is not worthy of further investigation. Otherwise, it will be concluded that the experimental therapy is worthy of further investigation. Safety monitoring will be done through a 6-week run-in for the first 10 patients to assess for pre-operative and post-operative toxicities and complications. Sequential boundaries will be used to monitor severe toxicity and complication rates. Accrual will be halted if excessive numbers of severe toxicity and complications in pre-operative and post-operative phases are seen. Tumor and blood-based biomarkers will be included as exploratory biomarkers. Clinical trial information: NCT05647265.