Clinical Trial ID: NCT03981796
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)
Endometrial cancer accounts for greater than 90 percent (%) of all uterine cancer. The majority of participants with endometrial cancer are diagnosed in early stages (Stage I or II) and receive surgery with curative intent; however, approximately 20% are diagnosed with advanced or metastatic disease (Stage III or IV) for which a surgical cure is not possible. Paclitaxel in combination with carboplatin has been shown to be efficacious against a variety of different tumor types, including non-small-cell-lung-carcinoma (NSCLC), ovarian cancer, endometrial cancer, and head and neck cancer. This study will evaluate the efficacy and safety of dostarlimab in combination with carboplatin-paclitaxel, the standard of care for participants with recurrent or primary advanced endometrial cancer. This study consists of a Screening Period, Treatment Period, an End of Treatment (EOT) Visit, a Safety Follow-up Visit, and a Survival Assessment Period. Participants will be randomized in a 1:1 ratio to receive either dostarlimab plus carboplatin paclitaxel or placebo plus carboplatin-paclitaxel.
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 Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V.1.1), in the following:
- All subjects with recurrent or primary advanced endometrial cancer
- Subjects with microsatellite instability-high (MSI-H) recurrent or primary advanced endometrial cancer.
Active Comparator: Dostarlimab plus Carboplatin-paclitaxel
Participants will be administered dostarlimab 500 milligram (mg) every 3 weeks (Q3W) as 30-minute infusion intravenously (IV) from Cycle 1 (each cycle is 21 days) to Cycle 6 and dostarlimab 1000 mg every 6 weeks (Q6W) (Cycle 7 until progression of disease, toxicity, withdrawal of consent, Investigator's decision, or death, whichever occurs first); followed by Carboplatin 5 mg/milliliter (mL)/minute (min) and paclitaxel 175 mg per square meter (mg/m^2) Q3W as 30-minute infusion IV from Cycle 1 to Cycle 6.
Placebo Comparator: Placebo plus carboplatin-paclitaxel
Participants will be administered placebo Q3W as 30-minute infusion IV from Cycle 1 to Cycle 6 and placebo Q6W (Cycle 7 until progression of disease, toxicity, withdrawal of consent, Investigator's decision, or death, whichever occurs first); followed by carboplatin 5mg/mL/min and paclitaxel 175 mg/m^2 Q3W as 30-minute infusion IV from Cycle 1 to Cycle 6.
Cervix; Other Female Genital; Ovary
Baptist MD Anderson Cancer Center
Female participant is at least 18 years of age, able to understand the study procedures, and agrees to participate in the study by providing written informed consent.
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 postoperational 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% 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; d) Participant has first recurrent disease and is chemotherapy naïve; e) Participant has received prior neo-adjuvant/adjuvant systemic chemotherapy 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 as follows: a) Absolute neutrophil count >= 1,500 cells/micro Liters (mcL); b) Platelets >= 100,000 cells/mcL; c) Hemoglobin >= 9 grams per deciliter (g/dL) or >= 5.6 millimoles per Liter (mmol/L); d) Serum creatinine <= 1.5× upper limit of normal (ULN) or calculated creatinine clearance >= 50 milliliter per minute (mL/min) using the Cockcroft-Gault equation for participants with creatinine levels > 1.5× institutional ULN; e) Total bilirubin <= 1.5× ULN and direct bilirubin <= 1× ULN; f) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5× ULN unless liver metastases are present, in which case they must be <= 5× ULN; g) International normalized ratio or prothrombin time (PT) <=1.5× ULN and activated partial thromboplastin time <=1.5× ULN. Participants receiving anticoagulant therapy must have a PT or partial thromboplastin within the therapeutic range of intended use of anticoagulants.
Participant must have a negative serum pregnancy test within 72 hours of the first dose of study medication, unless they are of nonchildbearing potential. Nonchildbearing potential is defined as follows: a) Participant is >= 45 years of age and has not had menses for > 1 year; b) A follicle-stimulating hormone value in the postmenopausal range upon screening evaluation if amenorrheic for < 2 years without a hysterectomy and oophorectomy; c) Posthysterectomy, postbilateral oophorectomy, or posttubal ligation.
Participants of childbearing potential must agree to use 2 adequate methods of contraception with their partners starting with the screening visit through 180 days after the last dose of study treatment.
Participant has received neo-adjuvant/adjuvant systemic chemotherapy for primary Stage III or IV disease and: a) has not had a recurrence or PD prior to entering the study OR b) has had a recurrence or PD within 6 months of completing chemotherapy treatment prior to entering the study.
Participant has had at least 1 recurrence of endometrial cancer.
Participant has received prior therapy with an anti-PD-1, anti-PD-L1, or 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 known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
Nct ID Number
Secondary Trial ID Number