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A study to determine whether the addition of Dostarlimab (TSR-042) delays recurrence of advanced endometrial cancer
EU CTIS ID: 2023-506551-23-00
What this study is testing
Part 1: To compare the progression-free survival (PFS) of subjects treated with dostarlimab plus carboplatin-paclitaxel followed by dostarlimab to subjects treated with placebo plus carboplatin-paclitaxel followed by placebo, 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 dMMR/MSI-H recurrent or primary advanced endometrial cancer To compare the overall survival (OS) of subjects treated with dostarlimab plus carboplatin paclitaxel followed by dostarlimab to subjects treated with placebo plus carboplatin-paclitaxel followed by placebo, in subjects with recurrent or primary advanced endometrial cancer. Part 2: To compare the PFS of subjects treated with dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib to subjects treated with placebo plus carboplatin-paclitaxel followed by placebo, as assessed by the Investigator per RECIST v.1.1, in the following: - All subjects with recurrent or primary advanced endometrial cancer. - Subjects with MMRp/MSS recurrent or primary advanced endometrial cancer. MMRp/MSS status will be determined by the MMR/MSI status entered at randomization.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- (Part 1 and Part 2): 1. Female subject at least 18 years of age, who is able to understand the study procedures and agrees to participate in the study by providing written informed consent.
- (Part 1 and Part 2): 2. Subject has histologically or cytologically proven endometrial cancer with recurrent or advanced disease.
- (Part 1 and Part 2): 3. Subject must provide adequate tumor tissue sample at Screening for MMR/MSI status testing. Note: The quality of the tumor tissue sample must be confirmed by the central laboratory during screening. Subjects should not be randomized without central laboratory confirmation.
- (Part 1 and Part 2): 4. Subject 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 1 of the following criteria: a) Subject 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 post-operative change should be biopsied and confirmed for the presence of tumor. b) Subject 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) Subject has primary Stage IIIC2 or Stage IV disease regardless of presence of evaluable or measurable disease. d) Subject has first recurrent disease and is naïve to systemic anticancer therapy. e) Subject has received prior neo-adjuvant/adjuvant systemic anticancer therapy and had a recurrence or PD ≥ 6 months after completing treatment (first recurrence). Note: Subjects with uterine sarcoma are not allowed.
- (Part 1 and Part 2): 5. Subject has an ECOG performance status of 0 or 1.
- (Part 1 and Part 2): 6. Subject has adequate organ function, defined as follows: a) Absolute neutrophil count ≥1,500 cells/μL b) Platelets ≥100,000 cells/μL c) Hemoglobin ≥9 g/dL or ≥5.6 mmol/L d) Serum creatinine ≤1.5× upper limit of normal (ULN) or calculated creatinine clearance ≥50 mL/min using the Cockcroft-Gault equation for subjects with creatinine levels >1.5 × institutional ULN e) Total bilirubin ≤1.5× ULN and direct bilirubin ≤1× ULN f) Aspartate aminotransferase and alanine aminotransferase ≤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. Subjects receiving anticoagulant therapy must have a PT or partial thromboplastin within the therapeutic range of the intended use of anticoagulants.
You likely can't join if
- (Part 1 and Part 2) 1. Subject has received neo-adjuvant/adjuvant systemic anticancer therapy for primary Stage III or IV disease and: a. has not had a recurrence or PD prior to first dose on the study OR b. has had a recurrence or PD within 6 months of completing anticancer therapy treatment prior to first dose on the study Note: Low-dose cisplatin given as a radiation sensitizer or hormonal therapies do not exclude subjects from study participation.
- (Part 1 and Part 2) 10. Subject has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- (Part 1 and Part 2) 11. Subject has not recovered (ie, 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. Note: Subjects with Grade ≤2 neuropathy, Grade ≤2 alopecia, or Grade ≤2 fatigue are an exception to this criterion and may qualify for the study.
- (Part 1 and Part 2) 12. Subject has not recovered adequately from AEs or complications from any major surgery prior to starting therapy.
- (Part 1 and Part 2) 13. Subject has a known hypersensitivity to carboplatin, paclitaxel, or dostarlimab components or excipients.
- (Part 1 and Part 2) 14. Subject 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.
See the full eligibility criteria
Who can join
- (Part 1 and Part 2): 1. Female subject at least 18 years of age, who is able to understand the study procedures and agrees to participate in the study by providing written informed consent.
- (Part 1 and Part 2): 2. Subject has histologically or cytologically proven endometrial cancer with recurrent or advanced disease.
- (Part 1 and Part 2): 3. Subject must provide adequate tumor tissue sample at Screening for MMR/MSI status testing. Note: The quality of the tumor tissue sample must be confirmed by the central laboratory during screening. Subjects should not be randomized without central laboratory confirmation.
- (Part 1 and Part 2): 4. Subject 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 1 of the following criteria: a) Subject 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 post-operative change should be biopsied and confirmed for the presence of tumor. b) Subject 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) Subject has primary Stage IIIC2 or Stage IV disease regardless of presence of evaluable or measurable disease. d) Subject has first recurrent disease and is naïve to systemic anticancer therapy. e) Subject has received prior neo-adjuvant/adjuvant systemic anticancer therapy and had a recurrence or PD ≥ 6 months after completing treatment (first recurrence). Note: Subjects with uterine sarcoma are not allowed.
- (Part 1 and Part 2): 5. Subject has an ECOG performance status of 0 or 1.
- (Part 1 and Part 2): 6. Subject has adequate organ function, defined as follows: a) Absolute neutrophil count ≥1,500 cells/μL b) Platelets ≥100,000 cells/μL c) Hemoglobin ≥9 g/dL or ≥5.6 mmol/L d) Serum creatinine ≤1.5× upper limit of normal (ULN) or calculated creatinine clearance ≥50 mL/min using the Cockcroft-Gault equation for subjects with creatinine levels >1.5 × institutional ULN e) Total bilirubin ≤1.5× ULN and direct bilirubin ≤1× ULN f) Aspartate aminotransferase and alanine aminotransferase ≤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. Subjects receiving anticoagulant therapy must have a PT or partial thromboplastin within the therapeutic range of the intended use of anticoagulants.
- (Part 1 and Part 2): 7. Contraceptive use by subjects should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a) A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: • The participant is a woman of nonchildbearing potential. OR • The participant is a WOCBP, using a contraceptive method that is highly effective (with a failure rate of <1% per year and, preferably, with low user dependency) during the Treatment Period and for at least 180 days after the last dose of study treatment and agrees not to donate eggs (ova or oocytes) for the purpose of reproduction during this period. (Note: Duration of contraceptive use may be longer than 180 days in order to comply with local requirements and local approved product labels). Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. The Investigator should evaluate the potential for contraceptive method failure (eg, noncompliance and recently initiated) in relationship to the first dose of study treatment. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as required by local guidelines) within 72 hours before the first dose of study treatment. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Note: The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Note: Additional requirements for pregnancy testing during and after study treatment are located in (Section 12.2.6.7).
- Part 2 only: 8. Subjects must have normal BP or adequately treated and controlled hypertension (systolic BP ≤140 mmHg and diastolic BP ≤90 mmHg).
- Part 2 only: 9. Subjects must be able to take medication PO.
What rules you out
- (Part 1 and Part 2) 1. Subject has received neo-adjuvant/adjuvant systemic anticancer therapy for primary Stage III or IV disease and: a. has not had a recurrence or PD prior to first dose on the study OR b. has had a recurrence or PD within 6 months of completing anticancer therapy treatment prior to first dose on the study Note: Low-dose cisplatin given as a radiation sensitizer or hormonal therapies do not exclude subjects from study participation.
- (Part 1 and Part 2) 10. Subject has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- (Part 1 and Part 2) 11. Subject has not recovered (ie, 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. Note: Subjects with Grade ≤2 neuropathy, Grade ≤2 alopecia, or Grade ≤2 fatigue are an exception to this criterion and may qualify for the study.
- (Part 1 and Part 2) 12. Subject has not recovered adequately from AEs or complications from any major surgery prior to starting therapy.
- (Part 1 and Part 2) 13. Subject has a known hypersensitivity to carboplatin, paclitaxel, or dostarlimab components or excipients.
- (Part 1 and Part 2) 14. Subject 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.
- (Part 1 and Part 2) 15. Subject is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, noninfectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent).
- (Part 1 and Part 2) 16. Subject is pregnant or breastfeeding or is expecting to conceive children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of study treatment.
- (Part 1 and Part 2) 17. Subject 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: 18. Subject has received prior therapy with a PARP inhibitor.
- Part 2 only: 19. Subject has clinically significant cardiovascular disease (eg, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, uncontrolled cardiac arrhythmia or unstable angina <6 months to enrollment, New York Heart Association Grade ≥2 congestive heart failure, serious cardiac arrhythmia requiring medication, Grade ≥2 peripheral vascular disease, and history of cerebrovascular accident within 6 months).
- (Part 1 and Part 2) 2. Subject has had >1 recurrence of endometrial cancer.
- Part 2 only: 20. Subject has any known history or current diagnosis of myelodysplastic syndrome or acute myeloid leukemia.
- Part 2 only: 21. Subject is at increased bleeding risk due to concurrent conditions (eg, major injuries or major surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
- Part 2 only: 22. Subject has a known hypersensitivity to niraparib components or excipients.
- Part 2 only: 23. Subject has participated in Part 1 of this study.
- (Part 1 and Part 2) 3. Subject has received prior therapy with an anti-PD-1, anti PD-L1, or anti programmed cell death-ligand 2 agent.
- (Part 1 and Part 2) 4. Subject 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. Note: Palliative radiation therapy to a small field ≥1 week prior to Day 1 of study treatment may be allowed.
- (Part 1 and Part 2) 5. Subject has a concomitant malignancy, or subject 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.
- (Part 1 and Part 2) 6. Subject has known uncontrolled central nervous system metastases, carcinomatosis meningitis, or both. Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of PD by imaging [using the identical imaging modality for each assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not been using steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a subject from study participation regardless of clinical stability.
- (Part 1 and Part 2) 7. Subject has a known history of HIV (HIV 1/2 antibodies).
- (Part 1 and Part 2) 8. Subject has known active hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid [qualitative] is detected).
- (Part 1 and Part 2) 9. Subject has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic therapy (eg, thyroid hormone or insulin)
The study team makes the final eligibility decision.
Where it's taking place
- Israel
- United Kingdom
- Turkey
- Ukraine
- Canada
- Belarus
- United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling female, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Israel; United Kingdom; Turkey; Ukraine; Canada; Belarus and 1 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.