A Three-arm Randomized Phase II Study of Dostarlimab Alone or With Bevacizumab Versus Nonplatinum Chemotherapy in Recurrent Gynecological Clear Cell Carcinoma: DOVE (APGOT-OV7/​ ENGOT-ov80 Study) (DOVE)

NCT 06023862

Brief Summary

Multicenter, randomized, open-label, phase II clinical study comparing Dostarlimab +/- Bevacizumab with standard chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells in patients with gynecological clear cell carcinomacancer arising from tissues that line organs.

198 subjects will be enrolled in this study and will be assigned to three groups in a 1:1:1 ratio.

1. Group A: Dostarlimab monotherapy
   • First 3 cycles: Dostalimab 500mg every 3 weeks, IV
   • 4 cycles ~ up to 24 months: Dostalimab 1000mg every 6 weeks, IV
2. Group B: Dostarlimab + Bevacizumab combination therapy
   • First 3 cycles: Dostalimab 500mg every 3 weeks, IV
   • 4 cycles ~ up to 24 months: Dostalimab 1000mg every 6 weeks, IV
   • Bevacizumab administered IV at 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity
3. Group C: General chemotherapy (one of Pegylated liposomal doxorubicin, Doxorubicin, Paclitaxel, and Gemcitabine)

Intervention/Treatment

• Drug: Dostarlimab
• Drug: Bevacizumab
• Drug: Doxorubicin
• Drug: Gemcitabine
• Drug: Paclitaxel
• Drug: Pegylated liposomal doxorubicin

Inclusion Criteria

1. Female patient is at least 18 years of age,
2. Patient has signed the Informed Consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. (ICF) and is able to comply with protocol requirements.
3. Patient with histologically proven confirmed recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, and vulva
   • Local review by gynecologic pathologista doctor who specialises in the study and diagnosis of disease through the examination and testing of body tissue required
   • ≥50% clear cell histology in case of mixed carcinoma
   • WT-1 neg (Only in case of ovarian cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs) Note: In the case of including non-ovarian clear cell carcinoma with more than 20 cases, the decision is made through discussion with the SPONSOR.
4. Patient with an Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status score of 0 or 1.
5. Disease progression within 12 months of completing platinum-based chemotherapy
6. 1-5 prior lines of therapies
7. Patient with measurable disease according RECIST 1.1 criteria
8. Availability of Tumor tissuea group of cells that work together to perform a function for translational research . – A formalin-fixed paraffin-embedded (FFPE) tumor block(preferred) or at least 20 slides (unstained, freshly cut, serial sections) must be submitted.
9. Patients who consent to fresh tumor biopsies
   • Confirmed with at least one lesion with location accessible to safely biopsyremoval of a section of tissue to analyse for cancer cells per the clinical judgement of the investigator
   • Note: If mandatory biopsies cannot be performed as per investigator’s clinical judgement, discussion and agreement between investigator and Sponsor are required.
10. Patient has adequate organ function, defined as follows:
    1. Absolute neutrophil count ≥ 1,500 cellsthe basic structural and functional unit of all living things/μL
    2. Plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding ≥ 100,000 cells/μL
    3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
    4. Serum creatinine ≤ 1.5× upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional ULN
    5. Total bilirubin ≤ 1.5× ULN (≤ 2.0 x ULN in patients with known Gilbert’s syndrome) or direct bilirubin ≤ 1× ULN
    6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN unless liver metastases are present, in which case they must be ≤ 5× ULN
    7. International normalized ratio or prothrombin time (PT) ≤1.5× ULN and activated partial thromboplastin time ≤1.5× ULN.Participants taking anticoagulants may be included on a stable dosethe amount of medication taken with a therapeutic INR <3.5. .
11. Patient must have a negative serum pregnancy test within 72 hours of the first dose of study medication, unless they are of non-childbearing potential. If a negative result cannot be confirmed by a urine test, a serum pregnancy test is required. Non-childbearing potential is defined as follows:
    1. Patient is ≥ 45 years of age and has not had menses for > 1 year.
    2. A follicle-stimulating hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body value in the postmenopausal range upon screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening evaluation if amenorrhoeic for < 2 years without a hysterectomycomplete or partial removal of the uterus and oophorectomyremoval of one (unilateral) or both (bilateral) ovaries.
    3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation:
       • Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body  , MRI, or CT scan.
       • Tubal ligation must be confirmed with medical records of the actual procedure.
       • Information must be captured appropriately within the site’s source documents.
12. Patient of childbearing potential must agree to use a highly effective method of contraception with their partners starting from time of consent through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient (Information must be captured appropriately within the site’s source documents).