• Part 1 and 2: Overall survival (OS) [ Time Frame: Up to 6 years and 9 months ]
  OS is defined as the time from randomization to the date of death by any cause.
• Part 1 and 2: Progression free survival (PFS) - Investigator assessment [ Time Frame: Up to 6 years and 9 months ]
  PFS based on Investigator Assessment is defined as the time from the date of randomization to the earliest date of assessment of PD or death by any cause in the absence of PD whichever occurs first per RECIST v.1.1.
• Part 1 and 2: Objective response rate (ORR) - BICR and Investigator assessment [ Time Frame: Up to 6 years and 9 months ]
  ORR based on BICR and Investigator assessment is defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR).
• Part 1 and 2: Duration of response (DOR) - BICR and Investigator assessment [ Time Frame: Up to 6 years and 9 months ]
  DOR based on BICR and Investigator assessment is defined as the time from first documentation of CR or PR until the time of first documentation of subsequent PD per RECIST v.1.1 or death by any cause in the absence of PD per RECIST v.1.1, whichever occurs first.
• Part 1 and 2: Disease control rate (DCR) - BICR and Investigator assessment [ Time Frame: Up to 6 years and 9 months ]
  DCR based on BICR and Investigator assessment is defined as the proportion of participants who have achieved a BOR of CR, PR, or stable disease (SD) per RECIST v.1.1.
• Part 1 and 2: Patient-reported outcomes (PROs) in the European Quality of Life scale, 5-Dimensions, 5-Levels (EQ-5D-5L) [ Time Frame: Up to 6 years and 9 months ]
  EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases.
• Part 1 and 2: PROs in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30 [Core]) [ Time Frame: Up to 6 years and 9 months ]
  EORTC QLQ-C30 is validated questionnaire to assess overall health-related quality of life in participants with cancer.
• Part 1 and 2: PROs in the EORTC Quality of Life Questionnaire (QLQ-EN24 [Endometrial Cancer Module]) [ Time Frame: Up to 6 years and 9 months ]
  EORTC QLQ-EN24 is a validated questionnaire to assess the overall health-related quality of life in participants with all stages of endometrial cancer.
• Part 1 and 2: Progression-free survival 2 (PFS2) [ Time Frame: Up to 6 years and 9 months ]
  PFS2 is defined as the time from treatment randomization to the date of assessment of progression on the first subsequent anticancer therapy following study treatment or death by any cause, whichever is earlier.
• Part 1 and 2: Number of participants with adverse events (AEs), Serious adverse events (SAEs), adverse event of special interests (AESIs), suspected unexpected serious adverse reaction (SUSAR) and treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 6 years and 9 months ]
• Part 1 and 2: Number of participants with clinically significant changes in clinical laboratory parameters, vital signs, physical examination, electrocardiogram (ECG) and participants reporting the intake of concomitant medication [ Time Frame: Up to 6 years and 9 months ]
• Part 1 and 2: Number of participants with Eastern Cooperative Oncology Group (ECOG) Performance Status Scores [ Time Frame: Up to 6 years and 9 months ]
  Performance status will be assessed using the ECOG scale, with Grades ranging from 0 to 5.
• Part 1 and 2: Minimum observed concentration (Cmin) and maximum observed concentration (Cmax) of dostarlimab (micrograms per milliliter) [ Time Frame: Predose (Day 1) and postdose (Day 1) of Cycles 1, 2, 6, 7, 10, 15, and 20 (Cycle 1, 2, 6 is 21 days and Cycle 7, 10, 15, 20 is 42 days) ]
  Blood samples to be collected predose (within 1 hour prior to infusion) and postdose (within 1 hour after the end of infusion) on Day 1 of Cycles 1, 2, 6, 7, 10, 15, and 20.
• Part 1 and 2: Cmin and Cmax at steady state of dostarlimab (micrograms per milliliter) [ Time Frame: Predose (Day 1) and postdose (Day 1) of Cycles 1, 2, 6, 7, 10, 15, and 20 (Cycle 1, 2, 6 is 21 days and Cycle 7, 10, 15, 20 is 42 days) ]
  Blood samples to be collected predose (within 1 hour prior to infusion) and postdose (within 1 hour after the end of infusion) on Day 1 of Cycles 1, 2, 6, 7, 10, 15, and 20.
• Part 2: Cmin and Cmax of niraparib (micrograms per milliliter) [ Time Frame: Predose (Day 1) and 3 hours postdose (Day 1) of Cycles 7 and 8 and Predose (Day 1) of Cycles 10 and 14 (each cycle is 42 days) ]
  Blood samples for niraparib PK to be collected predose (within 30 minutes before scheduled dose) and 3 hours postdose (+/-30 minutes) on Day 1 of Cycle 7 and Cycle 8. Additional blood samples for PK on Day 1 of Cycle 10 and Cycle 14 will be collected at predose (within 30 minutes before scheduled dose).
• Part 2: Cmin and Cmax at steady state of niraparib (micrograms per milliliter) [ Time Frame: Predose (Day 1) and 3 hours postdose (Day 1) of Cycles 7 and 8 and Predose (Day 1) of Cycles 10 and 14 (each cycle is 42 days) ]
  Blood samples for niraparib PK to be collected predose (within 30 minutes before scheduled dose) and 3 hours postdose (+/-30 minutes) on Day 1 of Cycle 7 and Cycle 8. Additional blood samples for PK on Day 1 of Cycle 10 and Cycle 14 will be collected at predose (within 30 minutes before scheduled dose).
• Part 1 and 2: Number of participants with anti-drug antibodies (ADA) against dostarlimab [ Time Frame: Predose (Day 1) ]
  All the predose samples collected for Dostarlimab PK analysis to be evaluated for the presence of ADAs and neutralizing antibody in a tiered approach using electrochemiluminescence.

• PFS based on blinded independent central review (BICR) [ Time Frame: Up to 5 years ]
• Overall survival (OS) [ Time Frame: Up to 5 years ]
• Objective response rate (ORR) [ Time Frame: Up to 5 years ]
• Duration of response (DOR) [ Time Frame: Up to 5 years ]
• Disease control rate (DCR) [ Time Frame: Up to 5 years ]
• Patient-reported outcomes (PROs) in the European Quality of Life scale, 5-Dimensions, 5-Levels (EQ-5D-5L) [ Time Frame: Up to 5 years ]
  EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in patients across diseases. EQ-5D-5L consists of a descriptive section of 5 questions, one related to each of: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Questions use a 5-point scale ("no problems", "slight problems", "moderate problems", "severe problems", "unable/extreme problems"). Scores are converted to an index value based on country-specific value sets, with a value of 0 representing "death" and 1 representing "perfect health"). The EQ-5D-5L also includes a visual-analogue scale of overall health on a 100-point scale (from "Worst imaginable health state" to "Best imaginable health state").
• Patient-reported outcomes (PROs) in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30 [Core]) [ Time Frame: Up to 5 years ]
  EORTC QLQ-C30 is a validated questionnaire to assess the overall health-related quality of life in patients with cancer and is composed of 30 questions including multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a global health status/quality of life scale (GHS/QOL), and six single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The QLQ-C30 employs a week recall period for all items and a 4-point scale for the functional and symptom scales/items with response categories "Not at all", "A little", "Quite a bit" and "Very much". The two items assessing GHS/QOL utilize a 7-point scale ranging from 1 ("Very Poor") to 7 ("Excellent"). Scores are averaged, and transformed to a 0-100 scale. A higher score on functional scales represents better function, and on symptom scales represents more severe symptoms.
• Patient-reported outcomes (PROs) in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-EN24 [Endometrial Cancer Module]) [ Time Frame: Up to 5 years ]
  EORTC QLQ-EN24 is a validated questionnaire to assess the overall health-related quality of life in patients with all stages of endometrial cancer, and consists of 24 questions including multi-item scales and single item measures. These include three functional scales (sexual interest, activity, and enjoyment), five symptom scales (lymphoedema, urological symptoms, GI symptoms, poor body image, and sexual/vaginal problems), and five single items (back/pelvis pain, tingling/numbness, muscular pain, hair loss, and taste change). Questions use a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to a 0-100 scale; a higher score represents a more severe overall side effect of treatment.
• Number and percentage of participants experiencing treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 5 years ]
• Number and percentage of participants with drug-related adverse events (AEs) [ Time Frame: Up to 5 years ]
• Number and percentage of participants discontinuing study drug due to an adverse event (AE) [ Time Frame: Up to 5 years ]

• Biological: Dostarlimab
  Participants will be administered dostarlimab
  Other Name: TSR-042
• Drug: Placebo
  Participants will be administered placebo
• Drug: Carboplatin
  Participants will be administered carboplatin
• Drug: Paclitaxel
  Participants will be administered paclitaxel
• Drug: Niraparib
  Participants will be administered niraparib

• Active Comparator: Arm 1: Participants receiving dostarlimab + Carboplatin-paclitaxel followed by dostarlimab
  Interventions:

  • Biological: Dostarlimab
  • Drug: Carboplatin
  • Drug: Paclitaxel
• Placebo Comparator: Arm 2: Participants receiving placebo + carboplatin-paclitaxel followed by placebo
  Interventions:

  • Drug: Placebo
  • Drug: Carboplatin
  • Drug: Paclitaxel
• Active Comparator: Arm 3: Participants receiving dostarlimab + carboplatin-paclitaxel followed by dostarlimab+niraparib
  Interventions:

  • Biological: Dostarlimab
  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Niraparib
• Placebo Comparator: Arm 4: Participants receiving placebo + carboplatin-paclitaxel followed by placebo
  Interventions:

  • Drug: Placebo
  • Drug: Carboplatin
  • Drug: Paclitaxel

Inclusion Criteria:

Part 1 and Part 2:

• Female participant is at least 18 years of age
• Participant has histologically or cytologically proven endometrial cancer with recurrent or advanced disease.
• Participant must have primary Stage III or Stage IV disease or first recurrent endometrial cancer with a low potential for cure by radiation therapy or surgery alone or in combination and meet at least one of the following criteria; a) Participant has primary Stage IIIA to IIIC1 disease with presence of evaluable or measurable disease per RECIST v.1.1 based on Investigator's assessment. Lesions that are equivocal or can be representative of post-operative change should be biopsied and confirmed for the presence of tumor; b) Participant has primary Stage IIIC1 disease with carcinosarcoma, clear cell, serous, or mixed histology (containing >=10 percent carcinosarcoma, clear cell, or serous histology) regardless of presence of evaluable or measurable disease on imaging; c) Participant has primary Stage IIIC2 or Stage IV disease regardless of the presence of evaluable or measurable disease; d) Participant has first recurrent disease and is naïve to systemic anticancer therapy; e) Participant has received prior neo-adjuvant/adjuvant systemic anticancer therapy and had a recurrence or PD >=6 months after completing treatment (first recurrence only).
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Participant has adequate organ function.
• Part 2 only:
• Participants must have normal blood pressure (BP) or adequately treated and controlled hypertension (systolic BP <=140 millimeter of mercury (mmHg) and diastolic BP <=90 mmHg).
• Participants must be able to take medication orally, by mouth (PO).

Exclusion Criteria:

• Part 1 and Part 2:
• Participant has received neo-adjuvant/adjuvant systemic anticancer therapy for primary Stage III or IV disease and: a) has not had a recurrence or PD prior to first dose on the study OR b) has had a recurrence or PD within 6 months of completing systemic anticancer therapy treatment prior to first dose on the study.
• Participant has had >1 recurrence of endometrial cancer.
• Participant has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-ligand 1 (anti-PD-L1), or anti-PD-ligand 2 (anti-PD-L2) agent.
• Participant has received prior anticancer therapy (chemotherapy, targeted therapies, hormonal therapy, radiotherapy, or immunotherapy) within 21 days or <5 times the half-life of the most recent therapy prior to Study Day 1, whichever is shorter.
• Participant has a concomitant malignancy, or participant has a prior non-endometrial invasive malignancy who has been disease-free for <3 years or who received any active treatment in the last 3 years for that malignancy. Non-melanoma skin cancer is allowed.
• Participant has known uncontrolled central nervous system metastases, carcinomatosis meningitis, or both.
• Participant has not recovered (i.e., to Grade <=1 or to Baseline) from cytotoxic therapy induced AEs or has received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin) within 21 days prior to the first dose of study drug.
• Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection requiring systemic therapy.
• Participant has received, or is scheduled to receive, a live vaccine within 30 days before first dose of study treatment, during study treatment, and for up to 180 days after receiving the last dose of study treatment.
• Part 2 only:
• Participant has clinically significant cardiovascular disease
• Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• Participant is at increased bleeding risk due to concurrent conditions.
• Participant has participated in Part 1 of this study.

• European Network of Gynaecological Oncological Trial Groups (ENGOT)
• GOG Foundation