A Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial Cancer (RUBY)

• ClinicalTrials.gov Identifier: NCT03981796
• Recruitment Status: Active, not recruiting
• First Posted: June 11, 2019
• Last Update Posted: August 12, 2022
• Sponsor: Tesaro, Inc.
• Collaborators: European Network of Gynaecological Oncological Trial Groups (ENGOT); GOG Foundation
• Information provided by (Responsible Party): Tesaro, Inc.

Tracking Information

• First Submitted Date: May 31, 2019
• First Posted Date: June 11, 2019
• Last Update Posted Date: August 12, 2022
• Actual Study Start Date: July 18, 2019
• Estimated Primary Completion Date: September 28, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 10, 2022)

• Parts 1 and 2: Progression-Free Survival (PFS) - investigator assessment [ Time Frame: Up to 6 years ]
• Part 1: Overall survival [ Time Frame: Up to 6 years ]

Original Primary Outcome Measures (submitted: June 7, 2019)

To compare the progression-free survival (PFS) of treatment with dostarlimab plus carboplatin-paclitaxel to treatment with placebo plus carboplatin-paclitaxel, as assessed by the Investigator per RECIST v.1.1, in the following: [ Time Frame: Up to 5 years ]

• All subjects with recurrent or primary advanced endometrial cancer
• Subjects with microsatellite instability-high (MSI-H) recurrent or primary advanced endometrial cancer

Current Secondary Outcome Measures (submitted: June 10, 2022)

• Part 2: Overall survival [ Time Frame: Up to 6 years ]
• Parts 1 and 2: Progression free survival (PFS) blinded independent central review (BICR) [ Time Frame: Up to 6 years ]
• Parts 1 and 2: Objective response rate (ORR) - BICR and Investigator assessment [ Time Frame: Up to 6 years ]
• Parts 1 and 2: Duration of response (DOR) - BICR and Investigator assessment [ Time Frame: Up to 6 years ]
• Parts 1 and 2: Disease control rate (DCR) - BICR and Investigator assessment [ Time Frame: Up to 6 years ]
• Parts 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 ]
  EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases.
• Parts 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 ]
  EORTC QLQ-C30 is validated questionnaire to assess overall health-related quality of life in participants with cancer.
• Parts 1 and 2: PROs in the EORTC Quality of Life Questionnaire (Endometrial Cancer Module [QLQ-EN24]) [ Time Frame: Up to 6 years ]
  EORTC QLQ-EN24 is a validated questionnaire to assess the overall health-related quality of life in participants with all stages of endometrial cancer.
• Parts 1 and 2: Progression-free survival 2 (PFS2) [ Time Frame: Up to 6 years ]
• Parts 1 and 2: Number of participants with adverse events (AEs), Serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 6 years ]
• Parts 1 and 2: Number of participants with clinically significant changes in clinical laboratory parameters, physical examination, electrocardiogram (ECG) and participants reporting the intake of concomitant medication [ Time Frame: Up to 6 years ]
• Parts 1 and 2: Change from Baseline in vital sign: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (Millimeters of mercury) [ Time Frame: Baseline and up to 6 Years ]
• Parts 1 and 2: Change from Baseline in vital sign: Heart Rate [ Time Frame: Baseline and up to 6 Years ]
• Parts 1 and 2: Change from Baseline in vital sign: Respiratory rate [ Time Frame: Baseline and up to 6 Years ]
• Parts 1 and 2: Change from Baseline in vital sign: Body temperature [ Time Frame: Baseline and up to 6 Years ]
• Parts 1 and 2: Number of participants with Eastern Cooperative Oncology Group (ECOG) Performance Status Scores [ Time Frame: Up to 6 years ]
  Performance status will be assessed using the ECOG scale, with status score ranging from 0 to 5.
• Parts 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) ]
• Parts 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) ]
• Part 2: Cmin and Cmax of niraparib (nanograms 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) ]
• Part 2: Cmin and Cmax at steady state of niraparib (nanograms 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) ]
• Parts 1 and 2: Number of participants with anti-drug antibodies (ADA) against dostarlimab [ Time Frame: Predose (Day 1) ]

Original Secondary Outcome Measures (submitted: June 7, 2019)

• 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial Cancer
• Official Title: A Phase 3, Randomized, Double-blind, Multicenter Study of Dostarlimab (TSR-042) Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Patients With Recurrent or Primary Advanced Endometrial Cancer (RUBY)
• Brief Summary: This is a 2 part study. Part 1 is to evaluate the efficacy and safety of dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus placebo plus carboplatin-paclitaxel followed by placebo; and Part 2 is to evaluate the efficacy and safety of dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo in participants with recurrent or primary advanced (Stage III or IV) endometrial cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The participant, Investigator, study staff, and the Sponsor study team and its representatives will be blinded to the assigned treatment.

Primary Purpose: Treatment

• Condition: Neoplasms

Intervention

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

Study Arms

• 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 matching dostarlimab
  • 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 matching dostarlimab
  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Placebo matching Niraparib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 10, 2022): 785
• Original Estimated Enrollment (submitted: June 7, 2019): 470
• Estimated Study Completion Date: December 23, 2026
• Estimated Primary Completion Date: September 28, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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;

  1. Participant has primary Stage IIIA to IIIC1 disease with presence of evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (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;
  2. Participant has primary Stage IIIC1 disease with carcinosarcoma, clear cell, serous, or mixed histology (containing greater than or equal to [>=] 10 percent carcinosarcoma, clear cell, or serous histology) regardless of presence of evaluable or measurable disease on imaging;
  3. Participant has primary Stage IIIC2 or Stage IV disease regardless of the presence of evaluable or measurable disease;
  4. Participant has first recurrent disease and is naïve to systemic anticancer therapy;
  5. Participant has received prior neo-adjuvant/adjuvant systemic anticancer therapy and had a recurrence or progression of disease (PD) >=6 months after completing treatment (first recurrence only).
• Participant has an 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 lesser than or equal to [<=] 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:

  1. has not had a recurrence or PD prior to first dose on the study OR
  2. 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 (that is [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 has not recovered adequately from AEs or complications from any major surgery prior to starting therapy.
• Participant is currently participating and receiving study treatment or has participated in a study of an investigational agent and received study treatment or used an investigational device within 4 weeks of the first dose of treatment.
• 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 received prior therapy with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor.
• 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

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belarus, Belgium, Canada, Czechia, Denmark, Finland, Germany, Greece, Hungary, Israel, Italy, Netherlands, Norway, Poland, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT03981796
• Other Study ID Numbers: 213361; ENGOT-EN6 ( Other Identifier: ENGOT ); GOG-3031 ( Other Identifier: GOG ); 4010-03-001 ( Other Identifier: Tesaro )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Tesaro, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Tesaro, Inc.
• Original Study Sponsor: Same as current

Collaborators

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

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: Tesaro, Inc.
• Verification Date: August 2022