Ovarian NeoplasmsPhase 2DOVENCT06023862
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)
A Phase 2 study testing Dostarlimab, Bevacizumab and Doxorubicin in people with Ovarian Neoplasms and Endometrial Neoplasms, run by Yonsei University at 27 sites in 7 countries.
Trial 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. 1. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Neoplasms, Endometrial Neoplasms, Uterine Cervical Neoplasms
- What is being tested?
- Dostarlimab, Bevacizumab and Doxorubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 198 participants
- Where
- 27 sitesin 7 countries
- Study dates
- 22 Jan 2024to 31 Dec 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 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 ultrasound, 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.
- 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).
Who cannot join
- 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.
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- 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 <!-- Not Allowed Tag Filtered --><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.
- Patient is currently participating and receiving study treatment or has participated in a study of an investigational agent and received study treatment or used an investigational device within 4 weeks of the first dose of treatment.
- Patient is considered a poor medical condition due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent).
- Patients with known history of non-infectious pneumonitis that required steroids or has current pneumonitis.
- Use of any of the following immunomodulatory agents within 28 days prior to the first dose of study drug:
- Interferons
- Interleukins
- Live vaccine Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. mRNA and adenoviral-based COVID-19 vaccines are considered non-live and are not exclusionary. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed as other killed vaccines, if done at least 2 weeks prior the first dose of study drug; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Patient who are pregnant or lactating, or plan to become pregnant or lactate during the expected duration of the study, from screening through 180 days after the last dose of study drug.
Trial locations and contacts
27 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
27 sites in 7 countries
Japan10 sites, 10 recruiting
- Recruiting
Fukushima Medical University Hospital
Fukushima, Fukushima, 960-1295
Soeda Shu, +81-(24)-547-1111, s-soeda@fmu.ac.jp
- Recruiting
Saitama Medical University International Medical Center
Hidaka, Saitama, 1397-1
Hasegawa Kosei, ＋81-(42)-984-4111, koseih@saitama-med.ac.jp
Kosei Hasegawa, Ph.D
- Recruiting
Kurume University Hospital
Kurume, Fukuoka, 830-0011
Nishio Shin, +81-(942)-35-3311, shinshin@med.kurume-u.ac.jp
- Recruiting
Niigata Cancer Center Hospital
Niigata, Niigata, 951-8566
Kikuchi Akira, +81-(25)-266-5111, akirak@niigata-cc.jp
- Recruiting
Tohoku University Hospital
Sendai, Miyagi, 980-8574
Shimada Muneaki, +81-(22)-717-7000, mshimada1221@yahoo.co.jp
- Recruiting
Tokushima University Hospital
Tokushima, Tokushima, 770-8501
Inui Hiroaki, +81-(88)-631-3111, hiroaki.inui@tokushima-u.ac.jp
- Recruiting
The Jikei University Hospital
Tokyo, Tokyo, 105-0003
Nishikawa Tadaaki, +81-(570)-03-2222, oh.brother.com@gmail.com
- Recruiting
The Cancer Institute Hospital Of JFCR
Tokyo, Tokyo, 135-8550
Yunokawa Mayu, +81-(3)-3520-0111, mayu.yunokawa@jfcr.or.jp
- Recruiting
Mie University Hospital
Tsu, Mie-ken, 514-8507
Kondo Eiji, +81-(59)-232-1111, eijikon@clin.medic.mie-u.ac.jp
- Recruiting
University of Tsukuba Hospital
Tsukuba, ㅊ Ibaraki, 305-8576
Satoh Toyomi, +81-(29)-853-3900, toyomi-s@md.tsukuba.ac.jp
South Korea7 sites, 7 recruiting
- Recruiting
National Cancer Center
Goyang-si
Myong Cheol Lim, Ph.D, mclim@ncc.re.kr
- Recruiting
Bundang Seoul National University Hospital
Seongnam-si
Dong Hoon Suh, Ph.D, sdhwcj@snubh.org
- Recruiting
Severance Hospital, Yonsei Health System
Seoul, Seoul, 03722
Jung-Yun Lee, Ph.D, JUNGYUNLEE@yuhs.ac
- Recruiting
Asan Medical Center
Seoul
Jeong-Yeol Park, Ph.D, obgyjypark@amc.seoul.kr
- Recruiting
Korea University Guro Hospital
Seoul
Hyun Woong Cho, Ph.D, limpcho82@korea.ac.kr
- Recruiting
Samsung Medical Center
Seoul
Byoung-Gie Kim, Ph.D, bksong.kim@samsung.com
- Recruiting
Seoul National University
Seoul
Jae-Won Kim, Ph.D, kjwksh@snu.ac.kr
Australia3 sites
- Active, not recruiting
Monash Medical Centre
Clayton, Clayton Rd.
- Active, not recruiting
Peter MacCallum Cancer Centre
Melbourne, Grattan Saint
- Active, not recruiting
Calvary Mater Newcastle
Waratah, Edith Saint
Taiwan3 sites
- Active, not recruiting
Taipei Veterans General Hospital
Taipei, Beitou District
- Active, not recruiting
Chang Gung Memorial Hospital
Taipei, Songshan District
- Active, not recruiting
National Taiwan University Hospital
Taipei, Zhongzheng
Singapore2 sites, 1 recruiting
- Active, not recruiting
National University Hospital
Singapore, Kent Ridge Rd
- Not yet recruiting
National University Hospital
Singapore
David Tan Shao Peng, Ph.D, David_sp_tan@nuhs.edu.sg
Hong Kong1 site
- Active, not recruiting
University of Hong Kong
Hong Kong, Pok Fu Ram
United Kingdom1 site
- Active, not recruiting
Guy's and St Thomas' NHS Foundation Trust
London, Monkton
About this study
Official title: A Three-arm Randomized Phase II Study of Dostarlimab Alone or With Bevacizumab Versus Nonplatinum Chemotherapy in Recurrent Gynecological Clear Cell Carcinoma: DOVE (APGOT-OV07/ ENGOT-ov80 Study)
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.
Read more
- 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
- 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
- Being tested
- Dostarlimab, Bevacizumab, Doxorubicin, Gemcitabine, Paclitaxel
- Medical subject headings
- Ovarian Neoplasms, Endometrial Neoplasms, Uterine Cervical Neoplasms, Vulvar Neoplasms, Vaginal Neoplasms, Adenocarcinoma, Clear Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DostarlimabDrug
Also called Jemperli
Intravenous (IV) infusion
BevacizumabDrug
Intravenous (IV) infusion
DoxorubicinDrug
Intravenous (IV) infusion
GemcitabineDrug
Intravenous (IV) infusion
PaclitaxelDrug
Intravenous (IV) infusion
Pegylated liposomal doxorubicinDrug
Intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Dostarlimab monotherapy Receives: Drug: Dostarlimab |
| Group B | Experimental | Dostarlimab + Bevacizumab combination therapy Receives: Drug: Dostarlimab; Drug: Bevacizumab |
| Group C | Active comparator | General chemotherapy (one of Pegylated liposomal doxorubicin, Doxorubicin, Paclitaxel, and Gemcitabine) Receives: Drug: Doxorubicin; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Pegylated liposomal doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to approximately 48 months
Secondary outcomes (9)
Objective Response Rate
the proportion of patients who have best overall response of either complete response (CR) or partial response (PR), as investigator assessment based on RECIST 1.1
Measured: Up to approximately 48 months
Disease control rate
the proportion of patients who have best overall response of CR, PR, or stable disease (SD) by investigator assessment per RECIST 1.1 . SD must be achieved at ≥ 7 weeks after randomization to be considered best overall response.
Measured: Up to approximately 48 months
Clinical benefit rate
the proportion of patients who have best overall response of CR, PR, or stable disease (SD) by investigator assessment per RECIST 1.1 . (duration of SD ≥ 23 weeks after randomization)
Measured: Up to approximately 48 months
Progression Free Survival 2
the time from initial randomization to the second objective disease progression (ie, after the first subsequent therapy) or death.
Measured: Up to approximately 72 months
Overall survival
the time from the date of randomization until death due to any cause
Measured: Up to approximately 72 months
Duration of Response Rate
Measured from the time of initial response until documented tumor progression.
Measured: Up to approximately 48 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Assessed by CTCAE v5.0 (by investigators).
Measured: Up to approximately 72 months
Time to first and second Subsequent Treatment
the time from the date of randomization to date of the first and second subsequent anticancer therapy or death.
Measured: Up to approximately 72 months
Response rate of subsequent therapies
the proportion of patients who have best overall response of either complete response (CR) or partial response (PR), as investigator assessment based on RECIST 1.1
Measured: Up to approximately 72 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2023
- Study start22 Jan 2024
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian NeoplasmsStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 198 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, JUNGYUN LEE, Yonsei University
- Investigators
- JUNGYUN LEE, Ph.D., Principal investigator, Severance Hospital, Yonsei University Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06023862
- Sponsor's protocol ID
- 4-2023-0794
- Acronym
- DOVE
- Status last verified
- Apr 2026
- First submitted
- 23 Aug 2023
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 39710508