A Study of Rucaparib and Nivolumab in People With Leiomyosarcoma

Exclusion Criteria

• •Uncontrolled intercurrent illness including current active or chronic infection requiring systemic therapy or the following cardiac criteria:
• •* Symptomatic congestive heart failure (NYHA classification III or IV) within 6 months
• •* Acute myocardial infarction ≤6 months prior to Day 1
• •* Grade ≥2 ventricular arrhythmia ≤6 months prior to Day 1
• •* History of cerebrovascular accident within 6 months before first dose of study drugs
• •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• •Evidence of clinically significant immunosuppression such as the following:
• •* Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
• •* Concurrent opportunistic infection
• •* Receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \> 10 mg/day of prednisone or equivalent within 7 days prior to enrollment. However, in the setting of non-immune mediated indications for steroid use, chronic/active low dose steroid use may be permitted at the discretion of the principal investigator. The dose of steroid allowed in this setting is also at the discretion of the principal investigator. (Use of inhaled or topical steroids is permitted.)
• •History or evidence of symptomatic autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other), or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past 2 years prior to enrollment. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease.
• •Known history of a positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• •History of non-viral hepatitis or cirrhosis
• •A history of alcohol abuse
• •Use of any live vaccines (e.g., against infectious diseases such as varicella) within 4 weeks (28 days) of initiation of study therapy
• •Has a known history of active TB (Bacillus Tuberculosis)
• •Prior therapy with a PARP inhibitor and/or PD-1/PD-L1 monoclonal antibody is not permitted.
• •* Patients who have not recovered from clinically significant adverse events of prior therapy to ≤ NCI CTCAE v5 Grade 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline. Except for AEs not considered a likely safety risk (e.g., alopecia, neuropathy)
• •* Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy events due to a previously administered agent.
• •Presence of a gastrointestinal condition that may affect drug absorption
• •Known allergy or reaction to any component of either study drug formulation
• •Has evidence of active, non-infectious pneumonitis.
• •Women who are pregnant or breast feeding
• •Subjects expecting to have a child within the projected duration of the trial, starting with the pre-screening or screening visit through 6 months after the last dose of study treatment(s) for women or 7 months for men.
• •Presence of any other concurrent malignancy requiring active therapy or thought to potentially interfere with the safe conduct or assessment of outcomes on this trial
• •Prior allogeneic stem cell transplantation or organ transplantation.