Comparing Dostarlimab with Bevacizumab for gynecological tumours

Exclusion

• −Has known sensitivity to study intervention components, Mo-Rez (antibody-drug conjugate, antibody, free cytotoxin GSK5757810A) and combination partner, or its excipients or other allergy that, in the opinion of the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →, contraindicates participation in the study.
• −Has untreated brain or CNS metastases or brain/CNS metastases rapidly progressing requiring urgent medical intervention.
• −Participants with known history of Human immunodeficiency virus (HIV).
• −Has a positive HCV antibody test result at screeningScreeningThe checks done before joining, to see whether a study fits.Read more → or within 3 months prior to the first dose of study intervention.
• −Has a second malignancy (except disease under study) that has progressed or required active treatment within the past 24 months except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas \[e.g., breast, cervix, bladder\] that have been resected with no evidence of metastatic disease.
• −Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant.
• −Has any following cardiological examination abnormality:
• −history in prior year of clinically significant or uncontrolled cardiac disease, acute myocardial infarction, NYHA Class III or IV congestive heart failure or clinically significant arrhythmia not controlled by standard of careStandard of careThe treatment normally given for a condition outside a study.Read more → therapy.
• −Corrected QT Interval (QTcF) \>450 millisecond (msec) or QTcF \>480 msec for participants with bundle branch block
• −Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis.
• −Has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is not considered a form of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis or insulin is not exclusionary).
• −Clinically significant bleeding symptoms, significant bleeding tendency, or bleeding tumors within 1 month prior to the first dose of study treatment.
• −Serious or poorly controlled hypertension, including history of hypertensive crisis, hypertensive encephalopathy; adjustment of antihypertensive medications due to poor blood pressure controlControl groupThe group a new treatment is measured against.Read more → within 2 weeks prior to the first dose of study treatment;
• −Has any active renal condition (e.g., infection, requirement for dialysis, or any other active significant renal condition or dehydrated condition that could affect the participant's safety). Note: renal obstruction successfully managed by stenting is permitted.
• −Has any serious and/or unstable medical condition (such as clinical symptoms of intestinal obstruction) or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant's safety, obtainment of informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more →, or compliance to the study procedures.
• −Exclusion criteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → of participants under armArmOne of the groups in a study, each receiving something different.Read more → Module 1 (Mo-Rez +Dostarlimab) Endometrial Cancer:
• −Has mesenchymal tumor of the uterus (uterine sarcoma).
• −Exclusion criteria of participants under arm Module 2 (Mo-Rez +/-Bevacizumab) Ovarian Cancer:
• −Participants with wound healing complications or incompletely healed wounds.
• −Participants with history or evidence of gastrointestinal perforation, tracheoesophageal fistula, or any grade 4 fistula; participants with gastrointestinal fistula, visceral fistula, or abdominal abscess within 6 months prior to the first dose, participants with history of osteonecrosis of the jaw.
• −Participants who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.
• −Participants with congenital bleeding diathesis, acquired coagulopathy, recent pulmonary haemorrhage/ haemoptysis (\> 2.5 mL of red blood or ½ teaspoon) within the last 3 months. Participants receiving treatment for thromboembolism are permitted as long as they have been on a stable dose of anticoagulation for at least 1 month.
• −Participant has history of congestive heart failure (CHF) or baselineBaselineYour starting measurements, taken before treatment begins.Read more → LVEF \<50% or institutional lower limits of normal.
• −Participant with history of nephrotic syndrome or grade 3 proteinuria. Participants has proteinuria as demonstrated by urine dipstick for proteinuria ≥2 (participants discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate ≤1 g of protein in 24 hours to be eligible).
• −Has an Alanine transaminase (ALT) value \>2.5x Upper Limit of Normal (ULN) and for participants with documented liver metastases/tumor infiltration has an ALT value \>5x ULN.
• −Has a total bilirubin value \>1.5x ULN.
• −Has documented presence of HBsAg and/or HBcAb, or HBsAb (except for presence of HBsAb attributable to previous vaccination) at screening or within 3 months prior to the first dose of study intervention.
• −Use of inhibitors of P-gp, breast cancer resistance protein (BCRP) or OATP1B1/1B3 within 7 days prior to the first dose of study drug. P-gp inducers should be discontinued for at least 14 days before the start of the study.
• −Has serious infections within 4 weeks prior to the first dose, including but not limited to infectious complications, bacteremia, severe pneumonia treated with intravenous antibiotics for ≥2 weeks.
• −Has had any major surgery within 28 days prior to enrolmentEnrolmentThe number of participants a study plans to include, or has included.Read more →.
• −Has experienced symptomatic pericarditis of any etiology within 6 months of study treatment or any of the following with prior immunotherapy: any imAE ≥ Grade 3, immune-mediated severe neurologic events of any-grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (SJS, TEN, or DRESS syndrome), or myocarditis of any grade.
• −Has received prior therapy with topoisomerase-1 inhibitors or ADC with topoisomerase-1 inhibitor warhead, or B7H4 targeted therapy.
• −Has received treatment with any cytotoxic chemotherapy drugs or other anti-tumor drugs (including endocrine therapy, molecular targeted therapy, immunotherapy, biotherapy, and investigational drug) within 30 days or 5 half-lives, whichever is shorter of a medicinal product prior to the first dose of study drug; or need to continue these drugs during the study.
• −Have received locoregional radiation therapy within 2 weeks prior to the first dose of study drug; more than 30% of bone marrow irradiation or wide-field radiation therapy within 4 weeks prior to the first dose of study treatment.