A Study of Dostarlimab (TSR-042) Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Patients With Recurrent or Primary Advanced Endometrial Cancer

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.
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Parts 1 and 2: Progression-Free Survival (PFS) - investigator assessment

Secondary Outcome

 Part 2: Overall survival

Condition

Neoplasms

Intervention

Dostarlimab

Study Arms / Comparison Groups

 Arm 1: Participants receiving dostarlimab + Carboplatin-paclitaxel followed by dostarlimab

Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Biological

Estimated Enrollment

785

Start Date

July 18, 2019

Completion Date

December 23, 2026

Primary Completion Date

September 28, 2022

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
      

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

GSK Clinical Trials, , 

Location Countries

Belarus

Location Countries

Belarus

NCT ID

NCT03981796

Organization ID

213361

Secondary IDs

ENGOT-EN6

Responsible Party

Sponsor

Study Sponsor

Tesaro, Inc.

Collaborators

 European Network of Gynaecological Oncological Trial Groups (ENGOT)

Study Sponsor

GSK Clinical Trials, Study Director, GlaxoSmithKline

Verification Date

August 2022