A phase 1b investigation of safety/efficacy of nivolumab and ABI-009 (nab-rapamycin) in advanced undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), chondrosarcoma (CS), osteosarcoma (OS) and Ewing sarcoma

TPS45 Background: Immune checkpoint inhibitors that promote sustained T cell activation may have synergistic activity with an mTOR inhibitor. Objectives: (1) To investigate the maximum tolerated dose of ABI-009, an mTOR inhibitor, when given sequentially with nivolumab, a PD-1 inhibitor, in advanced UPS, LPS, CS, OS and Ewing sarcoma; (2) To investigate the disease control rate (DCR), progression free survival (PFS), recurrence-free survival (RFS) and overall survival using nivolumab/ABI-009 combination therapy in advanced UPS, LPS, CS, OS and Ewing sarcoma; (3) To correlate disease control rate (DCR) based on Immune-related Response Criteria (irRECIST) with that based on RECIST v1.1, and to correlate PFS with PD-L1 and other biomarker expression in patients’ tumors. Methods: Forty to fifty previously treated patients with UPS, LPS, CS, OS or Ewing sarcoma will be enrolled. This is a phase 1b study using a defined dose of nivolumab 240 mg and escalating doses of ABI-009 56,75,100 mg/m2 given i.v. I. Dose Escalation Phase 1 Part of Study: The study will employ the standard “cohort of three” design. The maximum tolerated dose is defined as the highest safely tolerated dose, where not more than one patient experienced DLT, with the next higher dose level having at least two patients who experienced DLT. II. Expansion Phase 1b Part of Study: An additional 22-28 patients will receive ABI-009 at the MTD and defined doses of nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients in the expansion phase of the study may continue treatment until significant disease progression or unacceptable toxicity occurs. Statistical Considerations: Categorical variables will be summarized by the n and percent in each category. Point estimates for efficacy endpoint incidences will be accompanied by a 2-sided 95% exact binomial CI. Time to event endpoints will be summarized descriptively using the KM method. Clinical trial information: NCT03190174.