A multi-institutional open-label phase 1/2 trial of selumetinib in combination with Bromodomain Inhibitor and durvalumab in refractory/unresectable sarcomas including MPNST. The phase 1 portion will be separated in two parts and will be open to all patients with refractory/relapsed sarcomas. The phase 2 portion will be for patients with refractory/unresectable NF1-associated MPNST.~Part A will be a phase 1 dose escalation study of the combination with selumetinib and BI.~Part B will be phase 1 study combining the determined dose of selumetinib and BI from Part A with durvalumab.~Part C will be a phase 2 study combining selumetinib, BI with durvalumab in MPNST patients at the recommended doses from part B. A Simon's two-stage design will be used in the phase 2 trial to determine the clinical benefit in patients with unresectable or metastatic NF associated MPNST.~Statistical Plan Phase 1: Conventional dose escalation schema. Cohorts of 3 to 6 participants will be treated per dose level. At the RP2D or last dose level, the cohort may be expanded to up to an additional six participants for further pharmacokinetic and tolerability experience. The MTD/RP2D will be defined as the dose level immediately below the level at which ≥33% of participants in a cohort experience a DLT based on toxicities observed in the first drug therapy cycle.~Phase 2: A Simon's two-stage phase 2 trial of selumetinib, BI, and durvalumab to determine the safety and clinical benefit in patients with unresectable or metastatic MPNST Maximum Total Number of Subjects Phase 1: 6-24 participants Phase 2: 9 participants in first stage with additional 8 participants in stage 2.~Target Population Individuals ≥ 18 years of age with relapsed or refractory histologically confirmed sarcoma including MPNST. This may be amended when tolerability is established.~Anticipated Length of Study Maximum enrollment number for entire study is 41participants. It is expected that 15-25 participants will be enrolled per year, and enrollment is expected to be completed in 3 years with follow up after last participant accrual to be approximately 12 months.
A multi-institutional open-label phase 1/2 trial of selumetinib in combination with BI and durvalumab in refractory/unresectable sarcomas including MPNST. The phase 1 portion will be separated in two parts and will be open to all patients with refractory/relapsed sarcomas. The phase 2 portion will be for patients with refractory/unresectable NF1-associated MPNST.