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

Neoplasms Clinical Trial

— RUBY  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03981796
• Other study ID #: 213361
• Secondary ID: ENGOT-EN6GOG-303
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 18, 2019
• Est. completion date: November 26, 2026

Study information

• Verified date: May 2024
• Source: Tesaro, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 785
• Est. completion date: November 26, 2026
• Est. primary completion date: September 28, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endometrial Neoplasms
• Neoplasms

Intervention

Biological:
• Dostarlimab
Participants will be administered dostarlimab

Drug:
• Placebo matching dostarlimab
Participants will be administered placebo matching dostarlimab
• Carboplatin
Participants will be administered carboplatin
• Paclitaxel
Participants will be administered paclitaxel
• Niraparib
Participants will be administered niraparib
• Placebo matching Niraparib
Participants will be administered placebo matching Niraparib

Locations

Country	Name	City	State
Belarus	GSK Investigational Site	Grodno
Belarus	GSK Investigational Site	Minsk
Belgium	GSK Investigational Site	Aalst
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Liège
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montréal	Quebec
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Québec
Canada	GSK Investigational Site	Sault Ste. Marie	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Winnipeg	Manitoba
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Prague
Denmark	GSK Investigational Site	Aalborg
Denmark	GSK Investigational Site	Copenhagen
Denmark	GSK Investigational Site	Dk-2730 Herlev
Denmark	GSK Investigational Site	Odense
Finland	GSK Investigational Site	Kuopio
Finland	GSK Investigational Site	Tampere
Finland	GSK Investigational Site	Turku
Germany	GSK Investigational Site	Amberg	Bayern
Germany	GSK Investigational Site	Bad Homburg	Hessen
Germany	GSK Investigational Site	Dessau	Sachsen-Anhalt
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Giessen	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Jena	Thueringen
Germany	GSK Investigational Site	Karlsruhe	Baden-Wuerttemberg
Germany	GSK Investigational Site	Kiel	Schleswig-Holstein
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Offenbach	Hessen
Germany	GSK Investigational Site	Ravensburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Rosenheim	Bayern
Germany	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Ulm	Baden-Wuerttemberg
Germany	GSK Investigational Site	Wiesbaden	Hessen
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Thessaloniki
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Debrecen
Israel	GSK Investigational Site	Ashkelon
Israel	GSK Investigational Site	Beer Sheva
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Petach Tikva
Israel	GSK Investigational Site	Rehovot
Israel	GSK Investigational Site	Tel Aviv
Italy	GSK Investigational Site	Candiolo	Piemonte
Italy	GSK Investigational Site	Carpi (MO)	Emilia-Romagna
Italy	GSK Investigational Site	Lecce	Puglia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Ponderano
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Sassuolo	Emilia-Romagna
Italy	GSK Investigational Site	Trento	Trentino-Alto Adige
Italy	GSK Investigational Site	Udine	Friuli-Venezia-Giulia
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Eindhoven
Netherlands	GSK Investigational Site	Enschede
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Maastricht
Netherlands	GSK Investigational Site	Rotterdam
Norway	GSK Investigational Site	Bergen
Norway	GSK Investigational Site	Oslo
Norway	GSK Investigational Site	Stavanger
Norway	GSK Investigational Site	Tromso
Norway	GSK Investigational Site	Trondheim
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Gdynia
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Olsztyn
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Szczecin
Poland	GSK Investigational Site	Warszawa
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Cordoba
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid	Navarra
Spain	GSK Investigational Site	Málaga
Spain	GSK Investigational Site	San Sebastián
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Valencia
Sweden	GSK Investigational Site	Linköping
Sweden	GSK Investigational Site	Lund
Sweden	GSK Investigational Site	Stockholm
Sweden	GSK Investigational Site	Uppsala
Turkey	GSK Investigational Site	Adapazari
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Istanbul
Turkey	GSK Investigational Site	Istanbul
Turkey	GSK Investigational Site	Istanbul
Ukraine	GSK Investigational Site	Chernihiv
Ukraine	GSK Investigational Site	Kharkiv
United Kingdom	GSK Investigational Site	Brighton
United Kingdom	GSK Investigational Site	Cambridge
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Truro	Cornwall
United States	GSK Investigational Site	Albany	New York
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Augusta	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Charlottesville	Virginia
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Covington	Louisiana
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Deerfield Beach	Florida
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	Fort Wayne	Indiana
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Hinsdale	Illinois
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Kernersville	North Carolina
United States	GSK Investigational Site	Knoxville	Tennessee
United States	GSK Investigational Site	Lebanon	New Hampshire
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Mount Airy	North Carolina
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Newport Beach	California
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Palo Alto	California
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Providence	Rhode Island
United States	GSK Investigational Site	Rio Rancho	New Mexico
United States	GSK Investigational Site	Roanoke	Virginia
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	Savannah	Georgia
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Shreveport	Louisiana
United States	GSK Investigational Site	Springfield	Massachusetts
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Tulsa	Oklahoma
United States	GSK Investigational Site	Willow Grove	Pennsylvania
United States	GSK Investigational Site	Winston-Salem	North Carolina
United States	GSK Investigational Site	Zion	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Tesaro, Inc.	European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation

Countries where clinical trial is conducted

United States,  Belarus,  Belgium,  Canada,  Czechia,  Denmark,  Finland,  Germany,  Greece,  Hungary,  Israel,  Italy,  Netherlands,  Norway,  Poland,  Spain,  Sweden,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (1)

Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novak Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, Powell MA; RUBY Investigators. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-2158. doi: 10.1056/NEJMoa2216334. Epub 2023 Mar 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parts 1 and 2: Progression-Free Survival (PFS) - investigator assessment		Up to 6 years
Primary	Part 1: Overall survival		Up to 6 years
Secondary	Part 2: Overall survival		Up to 6 years
Secondary	Parts 1 and 2: Progression free survival (PFS) blinded independent central review (BICR)		Up to 6 years
Secondary	Parts 1 and 2: Objective response rate (ORR) - BICR and Investigator assessment		Up to 6 years
Secondary	Parts 1 and 2: Duration of response (DOR) - BICR and Investigator assessment		Up to 6 years
Secondary	Parts 1 and 2: Disease control rate (DCR) - BICR and Investigator assessment		Up to 6 years
Secondary	Parts 1 and 2: Patient-reported outcomes (PROs) in the European Quality of Life scale, 5-Dimensions, 5-Levels (EQ-5D-5L)	EQ-5D-5L is a validated questionnaire to assess the overall health-related quality of life in participants across diseases.	Up to 6 years
Secondary	Parts 1 and 2: PROs in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30 [Core])	EORTC QLQ-C30 is validated questionnaire to assess overall health-related quality of life in participants with cancer.	Up to 6 years
Secondary	Parts 1 and 2: PROs in the EORTC Quality of Life Questionnaire (Endometrial Cancer Module [QLQ-EN24])	EORTC QLQ-EN24 is a validated questionnaire to assess the overall health-related quality of life in participants with all stages of endometrial cancer.	Up to 6 years
Secondary	Parts 1 and 2: Progression-free survival 2 (PFS2)		Up to 6 years
Secondary	Parts 1 and 2: Number of participants with adverse events (AEs), Serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs)		Up to 6 years
Secondary	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		Up to 6 years
Secondary	Parts 1 and 2: Change from Baseline in vital sign: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (Millimeters of mercury)		Baseline and up to 6 Years
Secondary	Parts 1 and 2: Change from Baseline in vital sign: Heart Rate		Baseline and up to 6 Years
Secondary	Parts 1 and 2: Change from Baseline in vital sign: Respiratory rate		Baseline and up to 6 Years
Secondary	Parts 1 and 2: Change from Baseline in vital sign: Body temperature		Baseline and up to 6 Years
Secondary	Parts 1 and 2: Number of participants with Eastern Cooperative Oncology Group (ECOG) Performance Status Scores	Performance status will be assessed using the ECOG scale, with status score ranging from 0 to 5.	Up to 6 years
Secondary	Parts 1 and 2: Minimum observed concentration (Cmin) and maximum observed concentration (Cmax) of dostarlimab (micrograms per milliliter)		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)
Secondary	Parts 1 and 2: Cmin and Cmax at steady state of dostarlimab (micrograms per milliliter)		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)
Secondary	Part 2: Cmin and Cmax of niraparib (nanograms per milliliter)		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)
Secondary	Part 2: Cmin and Cmax at steady state of niraparib (nanograms per milliliter)		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)
Secondary	Parts 1 and 2: Number of participants with anti-drug antibodies (ADA) against dostarlimab		Predose (Day 1)