Clinical trial NCT03981796: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Neoplasms
Keywords: Dostarlimab
Carboplatin
Paclitaxel
Niraparib
Recurrent or primary advanced endometrial cancer
TSR-042
Lead sponsor: Tesaro, Inc.
Sponsor class: INDUSTRY
Collaborators: name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
name: GOG Foundation
First posted: 2019-06-11
Enrollment: 785
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Parts 1 and 2: Progression-Free Survival (PFS) - investigator assessment
timeFrame: Up to 6 years
measure: Part 1: Overall survival
timeFrame: Up to 6 years
Secondary outcomes:
measure: Part 2: Overall survival
timeFrame: Up to 6 years
measure: Parts 1 and 2: Progression free survival (PFS) blinded independent central review (BICR)
timeFrame: Up to 6 years
measure: Parts 1 and 2: Objective response rate (ORR) - BICR and Investigator assessment
timeFrame: Up to 6 years
measure: Parts 1 and 2: Duration of response (DOR) - BICR and Investigator assessment
timeFrame: Up to 6 years
measure: Parts 1 and 2: Disease control rate (DCR) - BICR and Investigator assessment
timeFrame: Up to 6 years
measure: Parts 1 and 2: Patient-reported outcomes (PROs) in the European Quality of Life scale, 5-Dimensions, 5-Levels (EQ-5D-5L)
timeFrame: Up to 6 years
measure: Parts 1 and 2: PROs in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30 [Core])
timeFrame: Up to 6 years
measure: Parts 1 and 2: PROs in the EORTC Quality of Life Questionnaire (Endometrial Cancer Module [QLQ-EN24])
timeFrame: Up to 6 years
measure: Parts 1 and 2: Progression-free survival 2 (PFS2)
timeFrame: Up to 6 years
measure: Parts 1 and 2: Number of participants with adverse events (AEs), Serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs)
timeFrame: Up to 6 years
measure: 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
timeFrame: Up to 6 years
measure: Parts 1 and 2: Change from Baseline in vital sign: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (Millimeters of mercury)
timeFrame: Baseline and up to 6 Years
measure: Parts 1 and 2: Change from Baseline in vital sign: Heart Rate
timeFrame: Baseline and up to 6 Years
measure: Parts 1 and 2: Change from Baseline in vital sign: Respiratory rate
timeFrame: Baseline and up to 6 Years
measure: Parts 1 and 2: Change from Baseline in vital sign: Body temperature
timeFrame: Baseline and up to 6 Years
measure: Parts 1 and 2: Number of participants with Eastern Cooperative Oncology Group (ECOG) Performance Status Scores
timeFrame: Up to 6 years
measure: Parts 1 and 2: Minimum observed concentration (Cmin) and maximum observed concentration (Cmax) of dostarlimab (micrograms per milliliter)
timeFrame: 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)
measure: Parts 1 and 2: Cmin and Cmax at steady state of dostarlimab (micrograms per milliliter)
timeFrame: 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)
measure: Part 2: Cmin and Cmax of niraparib (nanograms per milliliter)
timeFrame: 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)
measure: Part 2: Cmin and Cmax at steady state of niraparib (nanograms per milliliter)
timeFrame: 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)
measure: Parts 1 and 2: Number of participants with anti-drug antibodies (ADA) against dostarlimab
timeFrame: Predose (Day 1)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tempe
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Palo Alto
country: United States
facility: GSK Investigational Site
state: California
city: Deerfield Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Augusta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Savannah
country: United States
facility: GSK Investigational Site
state: Georgia
city: Savannah
country: United States
facility: GSK Investigational Site
state: Georgia
city: Hinsdale
country: United States
facility: GSK Investigational Site
state: Illinois
city: Zion
country: United States
facility: GSK Investigational Site
state: Illinois
city: Fort Wayne
country: United States
facility: GSK Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Iowa City
country: United States
facility: GSK Investigational Site
state: Iowa
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Covington
country: United States
facility: GSK Investigational Site
state: Louisiana
city: New Orleans
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Shreveport
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Lebanon
country: United States
facility: GSK Investigational Site
state: New Hampshire
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Rio Rancho
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Albany
country: United States
facility: GSK Investigational Site
state: New York
city: Bronx
country: United States
facility: GSK Investigational Site
state: New York
city: Mineola
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Kernersville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Mount Airy
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Hilliard
country: United States
facility: GSK Investigational Site
state: Ohio
city: Tulsa
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Wexford
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Willow Grove
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Providence
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Knoxville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Charlottesville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Roanoke
country: United States
facility: GSK Investigational Site
state: Virginia
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Grodno
country: Belarus
facility: GSK Investigational Site
city: Minsk
country: Belarus
facility: GSK Investigational Site
city: Aalst
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: LiEge
country: Belgium
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Winnipeg
country: Canada
facility: GSK Investigational Site
state: Manitoba
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sault Ste Marie
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: QuEbec
country: Canada
facility: GSK Investigational Site
city: Brno
country: Czechia
facility: GSK Investigational Site
city: Praha 2
country: Czechia
facility: GSK Investigational Site
city: Aalborg
country: Denmark
facility: GSK Investigational Site
city: Copenhagen
country: Denmark
facility: GSK Investigational Site
city: Herlev
country: Denmark
facility: GSK Investigational Site
city: Odense C
country: Denmark
facility: GSK Investigational Site
city: Roskilde
country: Denmark
facility: GSK Investigational Site
city: Kuopio
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Amberg
country: Germany
facility: GSK Investigational Site
city: Bad Homburg
country: Germany
facility: GSK Investigational Site
city: Dessau
country: Germany
facility: GSK Investigational Site
city: Dresden
country: Germany
facility: GSK Investigational Site
city: Essen
country: Germany
facility: GSK Investigational Site
city: Essen
country: Germany
facility: GSK Investigational Site
city: Frankfurt
country: Germany
facility: GSK Investigational Site
city: Giessen
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hannover
country: Germany
facility: GSK Investigational Site
city: Jena
country: Germany
facility: GSK Investigational Site
city: Karlsruhe
country: Germany
facility: GSK Investigational Site
city: Kiel
country: Germany
facility: GSK Investigational Site
city: Koeln
country: Germany
facility: GSK Investigational Site
city: Luebeck
country: Germany
facility: GSK Investigational Site
city: Mainz
country: Germany
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
city: Offenbach
country: Germany
facility: GSK Investigational Site
city: Ravensburg
country: Germany
facility: GSK Investigational Site
city: Rosenheim
country: Germany
facility: GSK Investigational Site
city: Tuebingen
country: Germany
facility: GSK Investigational Site
city: Ulm
country: Germany
facility: GSK Investigational Site
city: Wiesbaden
country: Germany
facility: GSK Investigational Site
city: Marousi
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Budapest
country: Hungary
facility: GSK Investigational Site
city: Debrecen
country: Hungary
facility: GSK Investigational Site
city: Ashkelon
country: Israel
facility: GSK Investigational Site
city: Beer-Sheva
country: Israel
facility: GSK Investigational Site
city: Haifa
country: Israel
facility: GSK Investigational Site
city: Jerusalem
country: Israel
facility: GSK Investigational Site
city: Petach Tikva
country: Israel
facility: GSK Investigational Site
city: Rehovot
country: Israel
facility: GSK Investigational Site
city: Tel Aviv
country: Israel
facility: GSK Investigational Site
city: Biella
country: Italy
facility: GSK Investigational Site
city: Candiolo
country: Italy
facility: GSK Investigational Site
city: Carpi MO
country: Italy
facility: GSK Investigational Site
city: Lecce
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Naples
country: Italy
facility: GSK Investigational Site
city: Rome
country: Italy
facility: GSK Investigational Site
city: Sassuolo
country: Italy
facility: GSK Investigational Site
city: Trento
country: Italy
facility: GSK Investigational Site
city: Udine
country: Italy
facility: GSK Investigational Site
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Eindhoven
country: Netherlands
facility: GSK Investigational Site
city: Enschede
country: Netherlands
facility: GSK Investigational Site
city: Groningen
country: Netherlands
facility: GSK Investigational Site
city: Maastricht
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Bergen
country: Norway
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Stavanger
country: Norway
facility: GSK Investigational Site
city: Troms
country: Norway
facility: GSK Investigational Site
city: Trondheim
country: Norway
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Gdynia
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Olsztyn
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Szczecin
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: MAlaga
country: Spain
facility: GSK Investigational Site
city: MAlaga
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: San SebastiAn
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Linkoping
country: Sweden
facility: GSK Investigational Site
city: Lund
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Uppsala
country: Sweden
facility: GSK Investigational Site
city: Adapazari
country: Turkey
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: Istanbul
country: Turkey
facility: GSK Investigational Site
city: Istanbul
country: Turkey
facility: GSK Investigational Site
city: Istanbul
country: Turkey
facility: GSK Investigational Site
city: Chernihiv
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Brighton
country: United Kingdom
facility: GSK Investigational Site
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Truro
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Mansoor R Mirza, Dana M Chase, Brian M Slomovitz, René dePont Christensen, Zoltán Novák, Destin Black, Lucy Gilbert, Sudarshan Sharma, Giorgio Valabrega, Lisa M Landrum, Lars C Hanker, Ashley Stuckey, Ingrid Boere, Michael A Gold, Annika Auranen, Bhavana Pothuri, David Cibula, Carolyn McCourt, Francesco Raspagliesi, Mark S Shahin, Sarah E Gill, Bradley J Monk, Joseph Buscema, Thomas J Herzog, Larry J Copeland, Min Tian, Zangdong He, Shadi Stevens, Eleftherios Zografos, Robert L Coleman, Matthew A Powell, . Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. The New England journal of medicine. 2023-Jun-08;388(23): 2145-2158. DOI : 10.1056/NEJMoa2216334 PMID: 36972026