A Randomized, Double-Blind, Phase 3 Comparison Of Platinum-Based Therapy With TSR-042 And Niraparib Versus Standard Of Care Platinum-Based Therapy As First-Line Treatment Of Stage III Or IV Nonmucinous Epithelial Ovarian Cancer

Ovarian cancer is a heterogeneous disease, characterized by complex molecular and genetic
changes. The high expression of vascular endothelial growth factor (VEGF) receptor,
programmed death receptor ligands 1 (PD-L1) expression, and deoxyribonucleic acid (DNA)
damage in ovarian tumors provide several targets for treatment and maintenance of disease
response. Given the unmet medical need of participants with advanced or metastatic ovarian
cancer, this study design will enable investigators to provide participants with current SOC
for ovarian cancer for the duration of the study. This is a global, multicenter, randomized,
double-blind, controlled Phase 3 study that will primarily compare the progression-free
survival (PFS) for participants receiving dostarlimab with SOC chemotherapy +/- bevacizumab
followed by niraparib and dostarlimab maintenance +/- bevacizumab versus participants
receiving SOC with chemotherapy followed by niraparib maintenance. This comparison will be
investigated both in the PD-L1 positive and overall population of newly diagnosed stage III
or IV advanced non-mucinous epithelial ovarian cancer participants and also to compare PFS of
all participants with Stage III or IV high-grade non-mucinous epithelial ovarian cancer
treated with platinum-based combination therapy, dostarlimab (TSR-042), and niraparib to SOC
platinum-based combination therapy. The currently recommended SOC therapy for the first line
treatment of Stage III or IV ovarian cancer is the combination of paclitaxel and carboplatin,
with or without concurrent and maintenance bevacizumab. Participants will receive SOC during
the chemotherapy Run-In period (cycle 1) before randomization to study treatment (cycle 2).
Concurrent bevacizumab use must be determined prior to randomization at cycle 2.

Inclusion criteria:

- Participants must be female, >=18 years of age, able to understand the study
procedures, and agree to participate in the study by providing written informed
consent.

- Participants with a histologically confirmed diagnosis of high-grade nonmucinous
epithelial ovarian (serous, endometrioid, clear cell, carcinosarcoma, and mixed
pathologies), fallopian tube, or peritoneal cancer that is Stage III or IV according
to the International Federation of Gynecology and Obstetrics (FIGO) or tumor, node and
metastasis staging criteria.

- All participants with Stage IV disease are eligible. This includes those with
inoperable disease, those who undergo primary debulking surgery (PDS) (R0 or
macroscopic disease), or those for whom neoadjuvant chemotherapy (NACT) is planned.

- Participants with Stage III are eligible if they meet protocol defined criteria.

- Participants must provide a blood sample for circulating tumor deoxyribonucleic acid
(ctDNA) homologous recombinant repair (HRR) testing at pre-screening or screening.

- Participant must provide a minimum of 1 formalin-fixed paraffin embedded (FFPE) block
slide at pre-screening or screening for PD-L1, homologous recombinant deficiency (HRD)
testing.

- Participants of childbearing potential must have a negative serum or urine pregnancy
test (beta human chorionic gonadotropin) within 3 days prior to receiving the first
dose of study treatment.

- Participants must be postmenopausal, free from menses for >1 year, surgically
sterilized, or willing to use highly effective contraception to prevent pregnancy or
must agree to abstain from activities that could result in pregnancy throughout the
study, starting with enrollment through 180 days after the last dose of study
treatment.

- Participants must have adequate organ function: Absolute neutrophil count (ANC)
>=1500/micro liter (μL;) Platelet count >=100000/μL; Hemoglobin >=9 grams per
deciliter (g/dL); Serum creatinine <=1.5 × upper limit of normal (ULN) or calculated
creatinine clearance >=60 milliliters per minute (mL/min) using the Cockcroft-Gault
equation; total bilirubin <=1.5 × ULN or direct bilirubin <=1.5 × ULN; AST and ALT
<=2.5 × ULN unless liver metastases are present, in which case they must be <=5 × ULN.

- Participants must have an ECOG score of 0 or 1.

- Participants must have normal blood pressure (BP) or adequately treated and controlled
hypertension (systolic BP <=140 millimeters of mercury (mmHg) and/or diastolic BP <=90
mmHg).

- Participants must agree to complete health related quality of life (HRQoL)
questionnaires throughout the study.

- Participants must be able to take oral medication.

Exclusion Criteria:

- Participant has mucinous, germ cell, transitional cell, or undifferentiated tumor.

- Participant has low-grade or Grade 1 epithelial ovarian cancer.

- Participant has not adequately recovered from prior major surgery.

- Participant is pregnant or is expecting to conceive children while receiving study
drug or for up to 180 days after the last dose of study drug. Participant is
breastfeeding or is expecting to breastfeed within 30 days of receiving the final dose
of study drug (women should not breastfeed or store breastmilk for use, during
niraparib treatment and for 30 days after receiving the final dose of study
treatment).

- Participant has known active central nervous system metastases, carcinomatous
meningitis, or both.

- Participant has clinically significant cardiovascular disease.

- Participant has a bowel obstruction by clinical symptoms or computed tomography (CT)
scan, subocclusive mesenteric disease, abdominal or gastrointestinal fistula,
gastrointestinal perforation, or intra-abdominal abscess.

- Participant has any known history or current diagnosis of myelodysplastic syndrome
(MDS) or acute myeloid leukemia (AML).

- Participant has been diagnosed and/or treated with any therapy for invasive cancer <5
years from study enrollment, completed adjuvant chemotherapy and/or targeted therapy
(example, trastuzumab) less than 3 years from enrollment, or completed adjuvant
hormonal therapy less than 4 weeks from enrollment.

- Participants with definitively treated non-invasive malignancies such as cervical
carcinoma in situ, ductal carcinoma in situ, Grade 1 or 2, Stage I endometrial cancer,
or non-melanomatous skin cancer are allowed.

- Participant is at increased bleeding risk due to concurrent conditions (example, major
injuries or major surgery within the past 28 days prior to start of study treatment
and/or history of hemorrhagic stroke, transient ischemic attack, subarachnoid
hemorrhage, or clinically significant hemorrhage within the past 3 months).

- Participant is immunocompromised.

- Participant has known active hepatitis B (example, hepatitis B surface antigen
reactive) or hepatitis C (example, hepatitis C virus ribonucleic acid [qualitative] is
detected).

- Participant is considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease, or uncontrolled infection.

- Participant has had investigational therapy administered within 4 weeks or within a
time interval less than at least 5 half-lives of the investigational agent, whichever
is longer, prior to the first scheduled day of dosing in this study.

- Participant has received a live vaccine within 14 days of planned start of study
therapy. Seasonal influenza vaccines that do not contain live viruses are allowed.

- Participant has a known contraindication or uncontrolled hypersensitivity to the
components of paclitaxel, carboplatin, niraparib, bevacizumab, dostarlimab, or their
excipients.

- Prior treatment for high-grade nonmucinous epithelial ovarian, fallopian tube, or
peritoneal cancer (immunotherapy, anti-cancer therapy, radiation therapy).

- Participant has an active autoimmune disease that has required systemic treatment in
the past 2 years. Replacement therapy is not considered a form of systemic therapy
(example, thyroid hormone or insulin).

- Participant has a diagnosis of immunodeficiency or is receiving systemic steroid
therapy or any other form of systemic immunosuppressive therapy within 7 days prior to
the first dose of study treatment.