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)

Recruiting now · Phase 2

Conditions studied: Ovarian Neoplasms, Endometrial Neoplasms, Uterine Cervical Neoplasms, Vulvar Cancer, Vagina Neoplasm, Clear Cell Carcinoma

In brief

Multicenter, randomized, open-label, phase II clinical study comparing Dostarlimab +/- Bevacizumab with standard chemotherapy in patients with gynecological clear cell carcinoma. 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)

Key facts

Study ID: NCT06023862
Run by: Yonsei University
People needed: 198
Starts: 2024-01-22
Expected to finish: 2029-12-31
Last updated by the study team: 2026-05-06

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

Female patient is at least 18 years of age,
Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements.
Patient with histologically proven confirmed recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, and vulva
Local review by gynecologic pathologist required
≥50% clear cell histology in case of mixed carcinoma
WT-1 neg (Only in case of ovarian cancer) 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.
Patient with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
Disease progression within 12 months of completing platinum-based chemotherapy
1-5 prior lines of therapies
Patient with measurable disease according RECIST 1.1 criteria
Availability of Tumor tissue 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.
Patients who consent to fresh tumor biopsies
Confirmed with at least one lesion with location accessible to safely biopsy 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.
Patient has adequate organ function, defined as follows:
Absolute neutrophil count ≥ 1,500 cells/μL
Platelets ≥ 100,000 cells/μL
Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
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
Total bilirubin ≤ 1.5× ULN (≤ 2.0 x ULN in patients with known Gilbert's syndrome) or direct bilirubin ≤ 1× ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN unless liver metastases are present, in which case they must be ≤ 5× ULN
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 dose with a therapeutic INR <3.5. .
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:
Patient is ≥ 45 years of age and has not had menses for > 1 year.
A follicle-stimulating hormone value in the postmenopausal range upon screening evaluation if amenorrhoeic for < 2 years without a hysterectomy and oophorectomy.

You may not qualify if…

Patient has had ≥ 6 prior lines of chemotherapy. Surgery of the recurrence is allowed.
Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Patient has received prior anticancer therapy (chemotherapy, 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 ≥ 1 week prior to Day 1 of study treatment may be allowed after discussion with the SPONSOR.
Patient with contraindication to chemotherapy or immune checkpoint inhibitor treatments or anti-angiogenic inhibitor
Patients with uncontrolled hypertension (defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥100 mmHg) based on an average of ≥ 3 BP readings on ≥ 2 sessions.
Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
Patients with current abdominal/pelvic fistula
Patient has a concomitant malignancy, or patient has a prior non-gynecological 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.
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.
Patient has a known history of human immunodeficiency virus (HIV; HIV ½ antibodies). Participants with known human immunodeficiency virus(HIV) are allowed if they meet all of the following criteria:
Cluster of differentiation 4(CD4) ≥350/μL and viral load <50 copies/mL.
No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months before enrollment.
No history of HIV-associated malignancy for the past 5 years.
Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV started >4 weeks before study enrollment.
Patient with presence of hepatitis B surface antigen or a positive hepatitis C antibody test result at screening or within 3 months before first dose of dostarlimab treatment.
Participants who are hepatitis B surface antigen positive may be enrolled if their HBV-DNA level is below the institutional lower limit.
Participants with chronic hepatitis B virus (HBV) infection who meet the criteria for anti-HBV therapy may be eligible if the participant is on a suppressive antiviral therapy before initiation of cancer therapy.
Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA polymerase chain reaction is obtained. Hepatitis C participants may be eligible if they both have completed curative therapy and have a hepatitis C viral load <quantifiable limit.
Patient has an active autoimmune disease that required systemic treatment in the past 2 years. Replacement therapy is not considered a form of (eg, thyroid hormone or insulin).
diagnosis immunodeficiency receiving steroid any other immunosuppressive within 7 days prior to first dose study treatment. Patients who have received acute and>/or low-dose systemic immunosuppressive medications (e.g,, a one-time dose of dexamethasone for nausea or chronic use of ≤ 10 mg/day of prednisone or dose equivalent corticosteroid) may be enrolled in the study after discussion with and approval by the Sponsor. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.
Patient has not recovered (to Grade ≤ 1) from previous anti-cancer therapy-induced adverse events (AEs).
Note: Patients with Grade ≤ 2 neuropathy, Grade ≤ 2 alopecia, or Grade ≤ 2 fatigue are an exception to this criterion and may qualify for the study.
Patient has not recovered adequately from AEs or complications from any major surgery prior to starting therapy. Major surgical procedures, other than for diagnosis, within 4 weeks prior to initiation of study treatment
Patient has a known hypersensitivity to bevacizumab or dostarlimab components or excipients.

Where it is running

National Cancer Center — Goyang-si, South Korea (enrolling)
Bundang Seoul National University Hospital — Seongnam-si, South Korea (enrolling)
Asan Medical Center — Seoul, South Korea (enrolling)
Korea University Guro Hospital — Seoul, South Korea (enrolling)
Samsung Medical Center — Seoul, South Korea (enrolling)
Seoul National University — Seoul, South Korea (enrolling)
Mie University Hospital — Tsu, Mie-ken, Japan (enrolling)
Tohoku University Hospital — Sendai, Miyagi, Japan (enrolling)
Niigata Cancer Center Hospital — Niigata, Niigata, Japan (enrolling)
Saitama Medical University International Medical Center — Hidaka, Saitama, Japan (enrolling)
Tokushima University Hospital — Tokushima, Tokushima, Japan (enrolling)
The Jikei University Hospital — Tokyo, Tokyo, Japan (enrolling)
The Cancer Institute Hospital Of JFCR — Tokyo, Tokyo, Japan (enrolling)
University of Tsukuba Hospital — Tsukuba, ㅊ Ibaraki, Japan (enrolling)
Kurume University Hospital — Kurume, Fukuoka, Japan (enrolling)
Fukushima Medical University Hospital — Fukushima, Fukushima, Japan (enrolling)
Severance Hospital, Yonsei Health System — Seoul, Seoul, South Korea (enrolling)
Guy's and St Thomas' NHS Foundation Trust — London, Monkton, United Kingdom
Calvary Mater Newcastle — Waratah, Edith Saint, Australia
Peter MacCallum Cancer Centre — Melbourne, Grattan Saint, Australia
University of Hong Kong — Hong Kong, Pok Fu Ram, Hong Kong
National University Hospital — Singapore, Kent Ridge Rd, Singapore
National University Hospital — Singapore, Singapore
Taipei Veterans General Hospital — Taipei, Beitou District, Taiwan
Chang Gung Memorial Hospital — Taipei, Songshan District, Taiwan

Full record on ClinicalTrials.gov

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