Study of Niraparib and TSR-042 in Recurrent Endometrial Cancer

Exclusion Criteria

• •Chemotherapy or biologic agents received within 4 weeks of starting study treatment.
• •Hormonal therapy within 2 weeks of starting study treatment.
• •Pelvic radiotherapy (as treatment of primary disease) within 4 weeks, or palliative radiotherapy encompassing \>20% of the bone marrow within 1 week of starting study treatment.
• •Previous treatment with a PARP inhibitor, or any other targeted therapy directed against the homologous recombination pathway.
• •Patients who are receiving any other investigational agents.
• •Ongoing ≥ Grade 2 toxicities related to prior cancer therapy, with the exceptions of alopecia, neuropathy, lymphopenia and skin depigmentation.
• •Received transfusion (platelets or red blood cells) ≤4 weeks of the first dose of study treatment.
• •Major surgery within 4 weeks of registration or ongoing clinically significant post-surgical complications. Study biopsy is not considered major surgery.
• •Known brain metastases, except if stable for greater than 28 days following definitive treatment. The patient must have no new or progressive signs or symptoms related to the CNS disease and must be either off or taking a stable dose of corticosteroids. A scan to confirm the absence of brain metastases is not required.
• •History of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).
• •History of bowel obstruction within 3 months, or other reason preventing effective oral administration of medication.
• •Immunocompromised patients e.g. Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C. Prior splenectomy is allowed.
• •Uncontrolled inter-current illness.
• •History of other malignancy ≤ 3 years prior to registration with the exceptions of a) cone-biopsied in situ carcinoma of the cervix uteri; b) basal or squamous cell carcinoma of the skin. All second malignancies in this context should be discussed with the Principal Investigator.
• •Previous treatment with anti PD-1, anti PD-L1, anti PD-L2, anti CTLA4 agents
• •History of fistula, or high-risk of developing a fistula.
• •Diagnosis of immunodeficiency or systemic steroid therapy or other form of immunosuppressive therapy within 7 days prior to initiating the protocol therapy.
• •Known history of human immunodeficiency virus (type 1 or 2 antibodies).
• •Known active hepatitis (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[qualitative\] is detected).
• •Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) Replacement therapy eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• •History of interstitial lung disease
• •Received a live vaccine within 14 days of initiating protocol therapy
• •History of ≥ Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.