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)

NCT06023862 | Recruiting Phase 2 DMC

• 1 other identifier: 4-2023-0794
• Study Type: interventional
• Target: 198
• Locations: 7 countries
• Sites: 27

Brief Summary

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.

• First 3 cycles: Dostalimab 500mg every 3 weeks, IV
• 4 cycles \~ up to 24 months: Dostalimab 1000mg every 6 weeks, IV
• 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
• Group C: General chemotherapy (one of Pegylated liposomal doxorubicin, Doxorubicin, Paclitaxel, and Gemcitabine)

Conditions

Ovarian Neoplasms; Endometrial Neoplasms; Uterine Cervical Neoplasms; Vulvar Cancer; Vagina Neoplasm; Clear Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  The time from the date of randomization until first documentation of disease progression, as determined by investigator assessment based on RECIST 1.1, or death due to any cause, whichever occurs first.

  Up to approximately 48 months

Secondary Outcomes (9)

• Objective Response Rate

  Up to approximately 48 months

• Disease control rate

  Up to approximately 48 months

• Clinical benefit rate

  Up to approximately 48 months

• Progression Free Survival 2

  Up to approximately 72 months

• Overall survival

  Up to approximately 72 months

Other Outcomes (2)

• Disease-related or Treatment-related Biomarkers

  At the end of study, Up to approximately 72 months

• Comparison of RECIST1.1 and i-RECIST assessment

  Throughout duration of study, Up to 48 months

Study Arms (3)

Group A

EXPERIMENTAL

Dostarlimab monotherapy

Drug: Dostarlimab

Group B

EXPERIMENTAL

Dostarlimab + Bevacizumab combination therapy

Drug: Dostarlimab; Drug: Bevacizumab

Group C

ACTIVE COMPARATOR

General chemotherapy (one of Pegylated liposomal doxorubicin, Doxorubicin, Paclitaxel, and Gemcitabine)

Drug: Doxorubicin; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Pegylated liposomal doxorubicin

Interventions

Dostarlimab DRUG

Intravenous (IV) infusion

Also known as: Jemperli

Group A; Group B

Bevacizumab DRUG

Intravenous (IV) infusion

Group B

Doxorubicin DRUG

Intravenous (IV) infusion

Group C

Gemcitabine DRUG

Intravenous (IV) infusion

Group C

Paclitaxel DRUG

Intravenous (IV) infusion

Group C

Pegylated liposomal doxorubicin DRUG

Intravenous (IV) infusion

Group C

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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
• 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:

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.

Sponsors & Collaborators

• Yonsei University: lead
• GlaxoSmithKline: collaborator

Study Sites (27)

Monash Medical Centre

Clayton, Clayton Rd., Australia

ACTIVE NOT RECRUITING

Calvary Mater Newcastle

Waratah, Edith Saint, Australia

ACTIVE NOT RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Grattan Saint, Australia

ACTIVE NOT RECRUITING

University of Hong Kong

Hong Kong, Pok Fu Ram, Hong Kong

ACTIVE NOT RECRUITING

Kurume University Hospital

Kurume, Fukuoka, 830-0011, Japan

RECRUITING

Fukushima Medical University Hospital

Fukushima, Fukushima, 960-1295, Japan

RECRUITING

Mie University Hospital

Tsu, Mie-ken, 514-8507, Japan

RECRUITING

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

RECRUITING

Niigata Cancer Center Hospital

Niigata, Niigata, 951-8566, Japan

RECRUITING

Saitama Medical University International Medical Center

Hidaka, Saitama, 1397-1, Japan

RECRUITING

Tokushima University Hospital

Tokushima, Tokushima, 770-8501, Japan

RECRUITING

The Jikei University Hospital

Tokyo, Tokyo, 105-0003, Japan

RECRUITING

The Cancer Institute Hospital Of JFCR

Tokyo, Tokyo, 135-8550, Japan

RECRUITING

University of Tsukuba Hospital

Tsukuba, ㅊ Ibaraki, 305-8576, Japan

RECRUITING

National University Hospital

Singapore, Kent Ridge Rd, Singapore

ACTIVE NOT RECRUITING

National University Hospital

Singapore, Singapore

NOT YET RECRUITING

Severance Hospital, Yonsei Health System

Seoul, Seoul, 03722, South Korea

RECRUITING

National Cancer Center

Goyang-si, South Korea

RECRUITING

Bundang Seoul National University Hospital

Seongnam-si, South Korea

RECRUITING

Asan Medical Center

Seoul, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, South Korea

RECRUITING

Samsung Medical Center

Seoul, South Korea

RECRUITING

Seoul National University

Seoul, South Korea

RECRUITING

Taipei Veterans General Hospital

Taipei, Beitou District, Taiwan

ACTIVE NOT RECRUITING

Chang Gung Memorial Hospital

Taipei, Songshan District, Taiwan

ACTIVE NOT RECRUITING

National Taiwan University Hospital

Taipei, Zhongzheng, Taiwan

ACTIVE NOT RECRUITING

Guy's and St Thomas' NHS Foundation Trust

London, Monkton, United Kingdom

ACTIVE NOT RECRUITING

Related Publications (1)

• Lee JY, Tan D, Ray-Coquard I, Lee JB, Kim BG, Van Nieuwenhuysen E, Huang RY, Tse KY, Gonzalez-Martin A, Scott C, Hasegawa K, Wilkinson K, Yang EY, Lheureux S, Kristeleit R. Phase II randomized study of dostarlimab alone or with bevacizumab versus non-platinum chemotherapy in recurrent gynecological clear cell carcinoma (DOVE/APGOT-OV7/ENGOT-ov80). J Gynecol Oncol. 2025 Jan;36(1):e51. doi: 10.3802/jgo.2025.36.e51. Epub 2024 Dec 16.

  PMID: 39710508 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms; Uterine Cervical Neoplasms; Vulvar Neoplasms; Vaginal Neoplasms; Adenocarcinoma, Clear Cell

Interventions

dostarlimab; Bevacizumab; Doxorubicin; Gemcitabine; Paclitaxel; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Uterine Cervical Diseases; Vulvar Diseases; Vaginal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• JUNGYUN LEE, Ph.D.

  Severance Hospital, Yonsei University Health System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

JUNGYUN LEE, Ph.D.

CONTACT

82)2-2228-2237; JUNGYUNLEE@yuhs.ac

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 23, 2023
• First Posted: September 5, 2023
• Study Start: January 22, 2024
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-04

Locations

AU (3); TW (3); GB (1); JP (10); KR (7); SG (2); HK (1)