Study to Estimate Efficacy of Combining Dostarlimab and Niraparib in Relapsed EOC After Treatment With PARPi

Exclusion Criteria

• •1. Highly symptomatic disease according to physician´s discretion, i.e. rapid remission is required.
• •2. Patients with mucinous endothelial ovarian cancer.
• •3. Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (e.g. germ cell tumors).
• •4. Ovarian tumors of low malignant potential (e.g. borderline tumors).
• •5. Malignancies other than ovarian cancer (EOC) within 5 years prior to registration, with the exception of those with a negligible risk of metastasis or death (e.g. 5-year OS rate \>90%) and treated with expected curative outcome (such as adequately treated non melanoma skin carcinoma, ductal carcinoma in situ, or stage I low grade uterine cancer).
• •6. More than two prior systemic anticancer regimens; maintenance therapies (e.g. with bevacizumab or PARPi) are not calculated as separate line.
• •7. More than two lines of PARPi therapies.
• •8. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted).
• •The following washout requirements for prior therapies/procedures must be observed:
• •g. surgery: ≥3 weeks prior to therapy
• •h. investigational therapy: within 4 weeks or within less than at least 5 half-lives, whichever is shorter, prior to therapy
• •i. radiation: radiation encompassing \>20% of bone marrow ≤2 weeks prior to therapy
• •9. Patient has any known history or current diagnosis of MDS or AML.
• •10. Prior treatment with immune checkpoint blockade therapies, anti-PD1, or anti-PD-L1 therapeutic antibodies or anti-CTLA4 or anti-TIM-3, or participating in AGO-OVAR 2.29 trial.
• •11. Treatment with systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-α) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to cycle 1, day 1.
• •12. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) within 2 weeks prior to cycle 1, day 1, or anticipated requirement for systemic immunosuppressive medications during the trial.
• •NOTE: The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g. fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
• •13. Administration of a live, attenuated vaccine within 30 days prior to cycle 1, day 1 or anticipation that such a live attenuated vaccine will be required during the study or within 5 months after the last dose of the investigational drugs. Influenza vaccination should be given during influenza season only. Patients must not receive live, attenuated influenza vaccination, for more information see section 5.9.2.
• •14. Current treatment with anti-viral therapy for HBV.
• •15. History of idiopathic pulmonary fibrosis (including pneumonitis), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) detected on screening chest CT scan is permitted.
• •16. Patients with a baseline QT prolongation \>470 milliseconds.
• •17. Patients that are receiving concomitant medications that prolong QTc and are unable to discontinue use for the duration of the study.
• •18. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to registration) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to registration) in case of suspected spinal cord compression.
• •19. History of autoimmune disease, including but not limited to dermatomyositis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• •20. Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV). Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
• •21. Persistent toxicities (≥CTCAE grade 2) with the exception of alopecia and neurotoxicity CTCAE grade 2.
• •22. Severe infection requiring oral or IV antibiotics within 4 days prior to registration, including but not limited to active tuberculosis or hospitalization for complications of infection, bacteraemia, or severe pneumonia. Patients receiving prophylactic antibiotics (e.g., to prevent urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• •23. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications.
• •24. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection and posterior reversible encephalopathy syndrome (PRES). This includes also any psychiatric disorder that prohibits obtaining informed consent.
• •25. Pregnancy, lactation, or intention to become pregnant and Women of childbearing potential (WOBCP) not protected by highly-effective contraceptive methods, including male contraception (e.g. condoms as a barrier method), during the study or within 6 months after the last dose of niraparib or dostarlimab.
• •26. Known hypersensitivity to infused protein products and to the components of niraparib or dostarlimab.
• •27. Participant has received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior to initiating protocol therapy.
• •28. Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \>4 weeks and was related to the most recent treatment.
• •29. Participant has received a transfusion (platelets or red blood cells) ≤4 weeks prior to initiating protocol therapy.