Study of Nivolumab With or Without Pazopanib in Metastatic or Unresectable Soft Tissue Sarcomas

Phase II Randomized Study of Nivolumab With or Without Pazopanib in Metastatic or Unresectable Soft Tissue Sarcomas After One Prior Line of Systemic Therapy or Ineligible to Receive an Anthracycline-based Treatment

This trial will assess whether nivolumab alone or nivolumab combined with pazopanib will be associated with an improvement in progression free survival (PFS) at 6 months

The investigators hypothesize that the nivolumab alone or nivolumab plus pazopanib will be associated with an improvement in progression free survival (PFS) at 6 months compared to historical controls of placebo and pazopanib alone respectively.

This is a randomized, Phase 2 study of nivolumab alone or nivolumab plus pazopanib in adult (≥ 18 years old) male and female subjects with unresectable or metastatic soft tissue sarcoma either ineligible to receive an anthracycline-based first line treatment or after one prior systemic therapy. Up to 33 and 46 subjects will be randomized (1:1) in the nivolumab and nivolumab plus pazopanib cohorts respectively, with a Simon two-stage design. Preliminary endpoint analysis will be performed when at least 18 subjects in the nivolumab cohort and 16 subjects in the nivolumab plus pazopanib cohort, have completed the first 12 cycles of nivolumab (6 months). Accrual duration is expected to be around 2 years.

Inclusion Criteria:

• Histologic diagnosis of metastatic or unresectable soft tissue or bone sarcoma
• No prior therapy with nivolumab in either cohorts or with pazopanib in the combination cohort
• At least one line of systemic therapy or ineligibility for an anthracycline based chemotherapy
• At least 2 distinct measurable metastatic sites
• Adequate organ and marrow function as defined by initial laboratory tests
• Life expectancy > 3 months
• Stable brain metastases for at least 4 weeks and no steroid dependence

Exclusion Criteria:

• Autoimmune disease Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drugs hazardous or obscure the interpretation of adverse events
• Concomitant therapy with any non-study immunotherapy regimens, cytotoxic chemotherapy, immunosuppressive agents, other investigation therapies Chronic use of systemic corticosteroids greater than prednisone 10 mg daily or its equivalent
• Women of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 5 months after cessation of study drug, or have a positive pregnancy test at baseline, or are pregnant or breastfeeding;
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical illness.