Patients will have tests and exams to see if they are eligible for the clinical trial. If
found eligible, the patient will receive treatment with Niraparib daily and TSR-042 by vein
every three weeks for 4 cycles then every six weeks.
This study has two parts in order to evaluate the efficacy of combination treatment with
Niraparib and TSR-042.
Patients will receive the study treatment as long as there is evidence that the tumor is not
growing or spreading and they are not having any unacceptable, bad side effects.
Patients will be monitored during treatment with tests and exams and after treatment
completion for up to 5 years.
1. Patient is female at least 18 years of age.
2. Patient has histologically proven recurrent or progressive cervix cancer
3. Patient has archival tumor tissue available or a fresh biopsy of recurrent or
persistent tumor must be obtained prior to study treatment initiation.
4. Patient has measurable lesions by RECIST v1.1.
5. Patient has an ECOG performance status of 0 to 1.
6. Patients must have received at least one or more prior systemic treatment regimen.
Chemotherapy with radiation is not considered systemic treatment.
7. Patient has adequate organ function, defined per protocol
8. Patient is able to take oral medications.
9. Participant receiving corticosteroids may continue as long as their dose is stable for
least 4 weeks prior to initiating protocol therapy.
10. Participant must agree to not donate blood during the study or for 90 days after the
last dose of study treatment.
11. If of childbearing potential, has a negative pregnancy test within 7 days prior to
taking study medication or agrees to abstain from activities that could result in
pregnancy from enrollment through 180 days after the last dose of study treatment, or
be of non-childbearing potential.
1. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Note: Patients with previously treated brain metastases may participate provided they
are stable for at least 4 weeks prior to the first dose of study treatment, and have
not been using steroids for at least 7 days prior to study treatment.
2. Known additional malignancy that required active treatment within the last 2 years.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
3. Patient is considered a poor medical risk that would interfere with cooperation with
the requirements of the study.
4. Received a transfusion (platelets or red blood cells) ≤4 weeks prior to initiating
5. Received colony stimulating factors (eg, granulocyte colony-stimulating factor,
granulocyte macrophage colony stimulating factor, or recombinant erythropoietin)
within 4 weeks prior initiating protocol therapy.
6. 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.
7. Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
8. Serious, uncontrolled medical disorder, nonmalignant systemic disease, or active,
9. Pregnant or breastfeeding, or expecting to conceive children within the projected
duration of the study and for 180 days after the last dose of study treatment.
10. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of study
11. Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
12. Known active hepatitis B or hepatitis C.
13. Active autoimmune disease that has required systemic treatment in the past 2 years
(i.e., 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.
14. Not recovered to ≤Grade 1 or to baseline from chemotherapy induced AEs. Note: Patient
with ≤ Grade 1 neuropathy or ≤ Grade 2 alopecia is an exception to this criterion and
may qualify for the study.
15. Currently participating and receiving study therapy or has participated in a study of
an investigational agent and received study therapy or used an investigational device
within 4 weeks of the first dose of treatment.
16. Prior cytotoxic chemotherapy, anticancer targeted small molecules (e.g., tyrosine
kinase inhibitors), hormonal agents within 5 half-lives, or monoclonal antibodies
(mAb) within 5 half-lives or 4 weeks (whichever is shorter) of that treatment prior to
study Day 1 or radiation therapy encompassing > 20% of the bone marrow within 2 weeks
or any radiation therapy within 4 weeks prior to study Day 1.
17. Major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have
recovered from any surgical effects.
18. Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
19. Received a live vaccine within 14 days of planned start of study therapy.
20. Prior treatment with a known PARP inhibitor.
21. Known hypersensitivity to niraparib or TSR-042 components or excipients.
22. Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the
exception of non-clinically significant lab abnormalities.
23. History of interstitial lung disease.