endometrial adenocarcinoma
Conditions
Interventions
Patients will be randomized 1:1 to receive either 4 cycles of dostarlimab followed by dostarlimab as maintenance
up to 2 years or 6 cycles of carboplatin-paclitaxel:
Arm A: Dostarlimab 500 mg, every
Sponsors
Hasegawa Kosei
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 1. Female patient is at least 18 years of age, 2. Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements. 3. Patient with histologically proven endometrial adenocarcinoma with recurrent or advanced disease. 4. Patient with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 5. Patient must have primary Stage IIIA to C2 or Stage IV disease or first recurrent endometrial cancer (see International Federation of Gynecology and Obstetrics staging FIGO Staging 18.1) without curative treatment by radiation therapy or surgery alone or in combination, and meet at least one of the following situations: a) Patient has primary Stage IIIA-IIIC1 with not amenable curative intent surgery or radiation b) Patient has primary Stage IIIC2 (with nodes involvement from the outset, not allowing a curative radiotherapy, or with remaining lumbo-aortic nodes after lumbo-aortic dissection, which cannot be treated by curative radiotherapy) or Stage IV disease. c) Patient has recurrent disease and is chemotherapy naive for recurrence or advanced / metastatic setting. d) Patient may have received prior irradiation for advanced endometrial cancer with or without radiosensitizing chemotherapy if > 2 weeks before the start of the study 6. Patient with evaluable disease (measurable and not measurable disease) according RECIST 1.1 criteria 7. Patient may have received prior neo-adjuvant/adjuvant systemic chemotherapy or loco-regional concomitant radio-chemotherapy for the primary cancer and had a recurrence >= 6 months after completing treatment (first recurrence only). 8. All histologic subtypes of endometrial adenocarcinoma could be included if MMRd/MSI-H, 9. Patient with MMRd/MSI-H status (first diagnosed by routine local IHC performed either on primitive tumour tissue or on relapse/metastatic tumour sample) is mandatory for inclusion. A central confirmation will be done before inclusion; in case of ambiguous result of central IHC (lack of positive internal control, heterogeneous loss of MMR protein expression), the MSI-H status will be assessed by PCR/NGS. 10. Availability of 1 block for MMR/MSI status centralized confirmation for IHC or NGS/PCR, and additional block(s) for Translational Research 11. Patient could have been previously treated with hormone therapy, for the metastatic/advanced disease 12. Patient may have received pelvic and lombo-aortic external beam +/- vaginal brachytherapy 13. Patient has adequate organ function, defined as follows: a) Absolute neutrophil count >= 1,500 cells/uL b) Platelets >= 100,000 cells/uL c) Hemoglobin >= 9 g/dL or >= 5.6 mmol/L d) Serum creatinine == 50 mL/min using the Cockcroft-Gault equation for patients with creatinine levels > 1.5 x institutional ULN e) Total bilirubin =< 1.5 x ULN (=< 2.0 x ULN in patients with known Gilberts syndrome) or direct bilirubin =< 1 x ULN f) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN unless liver metastases are present, in which case they must be =< 5 x ULN g) International normalized ratio or prothrombin time (PT) =<1.5 x ULN and activated partial thromboplastin time =<1.5 x ULN. Patients receiving anticoagulant therapy must have a PT or partial thromboplastin within the therapeutic range of intended use of anticoagulants. 14. Patient must have a negative serum pregnancy test within 72 hours prior to the fir
Exclusion criteria
Exclusion criteria: 1. Patient has received neoadjuvant/adjuvant systemic chemotherapy for primary Stage III or IV disease and has had a recurrence or PD within 6 months of completing this chemotherapy treatment prior to entering the study. Note: Low-dose cisplatin given as a radiation sensitizer or hormonal therapies do not exclude patients from study participation. 2. Patient has had > 1 recurrence of endometrial cancer, treated with chemotherapy. Surgery of the recurrence is allowed. 3. Patient previously treated with systemic chemotherapy for noncurable advanced disease or metastatic disease 4. Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 5. Patient has received prior anticancer therapy for advanced or metastatic disease (targeted therapies, hormonal therapy, radiotherapy) 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 greater than or equal to 1 week prior to Day 1 of study treatment may be allowed. 6. Patient with contraindication to chemotherapy or checkpoint inhibitor treatments 7. Patient has a concomitant malignancy, or patient has a prior nonendometrial 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. 8. Patient has known uncontrolled central nervous system metastases, carcinomatosis meningitis, or both. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of disease progression 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 patient from study participation regardless of clinical stability. 9. Patient has a known history of human immunodeficiency virus (HIV; HIV 1 or 2 antibodies). 10. Patient has known active viral infection of hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid qualitative detection). 11. Patient 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). 12. Patient 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. 13. Patient has not recovered (ie, to Grade less than or equal to 1 or to baseline) from cytotoxic therapy-induced adverse events (AEs). Note: Patients with Grade less than or equal to 2 neuropathy, Grade less than or equal to 2 alopecia, or Grade less than or equal to 2 fatigue are an exception to this criterion and may qualify for the study. 14. Patient has not recovered adequately from AEs or complications from any major surgery prior to starting therapy. 15. Patient has a known hypersensitivity to carboplatin, paclitaxel, or dostarlimab components or excipients. Patient is currently participating and receiving study treatment or has participated in a study of an investigational agent and received study treatment or us
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) assessed per BICR (Blinded Independent Central Review) defined as the time from the date of randomization until objective tumor progression based on RECIST 1.1 by BICR (Blinded Independent Central Review), or death due to any cause, whichever occurs first. Patients alive and free of progression will be censored at the last disease assessment date. | — |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Japan, Singapore, South Korea, Spain, Switzerland, Turkiye, United Kingdom
Contacts
Public ContactClinical Trial Coordinating Office
CMIC Co., Ltd.
Outcome results
None listed