A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer

NCT ID: NCT06072781

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

270 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-18

Study Completion Date

2031-02-09

Brief Summary

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This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with defactinib versus Investigator's choice of treatments (ICT) in subjects with recurrent LGSOC who have progressed on a prior platinum-based therapy.

Detailed Description

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This international, randomized, open-label, Phase 3 study will compare the investigational combination of avutometinib plus defactinib versus Investigator's Choice of Treatments (ICT) in patients with recurrent LGSOC who have progressed on a prior platinum-based therapy. Avutometinib and defactinib are both types of drugs called kinase inhibitors. Kinase inhibitors block cancer cell growth. The study will compare the progression-free survival (PFS) of the combination of avutometinib plus defactinib versus ICT. The study will also evaluate the effect of the combination on safety, overall survival, other efficacy endpoints, and health-related quality of life and disease related symptoms. The study is being conducted by gynecological cancer specialists. Patients who are eligible and agree to participate in this study will be treated with either a combination of avutometinib with defactinib, or with one of four standard of care NCCN and ESMO treatment recommendations for recurrent LGSOC, and then with subsequent follow up appointments. Patients who originally received one of the standards of care treatments who are determined to have progressive disease may be eligible to crossover to receive the investigational combination avutometinib plus defactinib.Avutometinib and defactinib are investigational drugs that have not been approved by the U.S. Food and Drug Administration (FDA)

Conditions

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Low Grade Serous Ovarian Cancer

Keywords

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Low Grade Serous Ovarian Cancer KRAS KRAS wt KRAS mt

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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avutometinib + defactinib

Avutometinib 3.2 mg, PO, twice weekly for 21 days on, 7 days off in a 28-day (4 weeks) cycle in combination with defactinib 200 mg, PO, twice daily for 21 days on, 7 days off in a 28-day(4 week) cycle.

Group Type EXPERIMENTAL

avutometinib

Intervention Type DRUG

Avutometinib: administered orally

Defactinib

Intervention Type DRUG

Defactinib: administered orally

Investigator Choice of Treatment (ICT)

Patients will receive one of the following therapies as determined by the Investigator:

* Pegylated liposomal doxorubicin: 40 mg/m2 IV on Day 1 of each 28-day (4 week) cycle.
* Paclitaxel: 80 mg/m2 IV on Days 1, 8, and 15 of each 28-day (4 week) cycle.
* Anastrozole: 1 mg, PO, once daily of each 28-day (4 week) cycle.
* Letrozole: 2.5 mg, PO, once daily of each 28-day (4 week) cycle.

Group Type ACTIVE_COMPARATOR

Paclitaxel

Intervention Type DRUG

administered intravenously

Letrozole

Intervention Type DRUG

administered orally

Anastrozole

Intervention Type DRUG

administered orally

Pegylated liposomal doxorubicin

Intervention Type DRUG

administered intravenously

Interventions

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Paclitaxel

administered intravenously

Intervention Type DRUG

Letrozole

administered orally

Intervention Type DRUG

Anastrozole

administered orally

Intervention Type DRUG

avutometinib

Avutometinib: administered orally

Intervention Type DRUG

Defactinib

Defactinib: administered orally

Intervention Type DRUG

Pegylated liposomal doxorubicin

administered intravenously

Intervention Type DRUG

Other Intervention Names

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avutometinib (VS-6766) defactinib (VS-6063) Caelyx, Doxil, Lipodox Nov-Onxol, Onxol, Navaplus, Taxol Femara Arimidex

Eligibility Criteria

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Inclusion Criteria

Patients may be eligible for inclusion in the study if they meet the following criteria:

1. Histologically proven LGSOC (ovarian, fallopian, peritoneal)
2. Documented mutational status of KRAS by a validated tumor-tissue based diagnostic test.
3. Suitable for treatment with at least one of the Investigator's Choice of Treatments:pegylated liposomal doxorubicin, paclitaxel, letrozole, anastrozole.
4. Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
5. Measurable disease according to RECIST v1.1.
6. An Eastern Cooperative Group (ECOG) performance status ≤ 1.
7. Adequate organ function.
8. Adequate recovery from toxicities related to prior treatments.
9. For patients with reproductive potential, a negative pregnancy test must be confirmed and agreement to use highly effective method of contraceptive.
10. Willingness to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria

Patients will be excluded from the study if they meet any of the following criteria:

1. Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
2. Co-existing high-grade serous ovarian cancer or mixed histology.
3. Prior treatment with avutometinib, defactinib, or other FAK inhibitors.
4. History of prior malignancy with recurrence \<3 years from the time of enrollment.
5. Major surgery within 4 weeks, minor surgery within 1 week, or palliative radiotherapy within 1 week of the first dose of study intervention.
6. Symptomatic brain metastases requiring steroids or other interventions, known leptomeningeal metastases, or spinal cord compression.
7. An active skin disorder that has required systemic therapy within one year of the first dose of study intervention.
8. History of medically significant rhabdomyolysis.
9. For subjects with prior MEK or RAF exposure, Grade 4 toxicity is deemed related to the MEK inhibitor.
10. Symptomatic bowel obstruction within 3 months of the first dose of study intervention
11. Concurrent ocular disorders.
12. Concurrent heart disease or severe obstructive pulmonary disease.
13. Active or past medical history of interstitial lung disease/pneumonitis, including drug-induced or radiation pneumonitis, pulmonary fibrosis, or adult respiratory distress syndrome (ARDS).
14. Subjects with the inability to swallow oral medications.
15. History of hypersensitivity to any of the active agents or ingredients of study intervention: peanut, soya, polyoxyl castor oil, etcetc.). Prior hypersensitivity to anthracyclines or anthracenediones if the use of pegylated liposomal doxorubicin (PLD) is planned.
16. Pregnant or breastfeeding.
17. Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic therapy.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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GOG Foundation

NETWORK

Sponsor Role collaborator

European Network of Gynaecological Oncological Trial Groups (ENGOT)

OTHER

Sponsor Role collaborator

Australia New Zealand Gynaecological Oncology Group

OTHER

Sponsor Role collaborator

Korean Gynecologic Oncology Group

OTHER

Sponsor Role collaborator

Verastem, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rachel Grisham, MD

Role: PRINCIPAL_INVESTIGATOR

GOG Foundation

Susana Banerjee, MBBS, MA, PhD

Role: PRINCIPAL_INVESTIGATOR

European Network of Gynecological Oncological Trial Groups (ENGOT)

Craig Berman Verastem Medical Monitor

Role: STUDY_DIRECTOR

[email protected]

Locations

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HonorHealth

Phoenix, Arizona, United States

Site Status RECRUITING

University of Arkansas

Little Rock, Arkansas, United States

Site Status RECRUITING

UCLA Health

Los Angeles, California, United States

Site Status RECRUITING

UC Davis

Sacramento, California, United States

Site Status RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Yale University

New Haven, Connecticut, United States

Site Status RECRUITING

Florida Cancer Specialists - South

Fort Myers, Florida, United States

Site Status RECRUITING

Mount Sinai

Miami Beach, Florida, United States

Site Status RECRUITING

AdventHealth

Orlando, Florida, United States

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

Florida Cancer Specialists Research East

West Palm Beach, Florida, United States

Site Status RECRUITING

Winship Cancer Institute at Emory University

Atlanta, Georgia, United States

Site Status RECRUITING

NorthShore University HealthSystem

Evanston, Illinois, United States

Site Status RECRUITING

Louisiana State University

New Orleans, Louisiana, United States

Site Status RECRUITING

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status RECRUITING

Karmanos Cancer Center

Detroit, Michigan, United States

Site Status RECRUITING

Minnesota Oncology Hematology

Minneapolis, Minnesota, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Atrium Health

Charlotte, North Carolina, United States

Site Status RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status RECRUITING

Ohio State

Hilliard, Ohio, United States

Site Status RECRUITING

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Willamette Valley Cancer Institute

Eugene, Oregon, United States

Site Status RECRUITING

Northwest Cancer Specialists

Portland, Oregon, United States

Site Status RECRUITING

Asplundh Cancer Pavilion | Jefferson Health

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Allegheny Health Network

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Texas Oncology Central

Austin, Texas, United States

Site Status RECRUITING

Texas Oncology-Fort Worth Cancer Center

Fort Worth, Texas, United States

Site Status RECRUITING

Houston Methodist

Houston, Texas, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Texas Oncology

San Antonio, Texas, United States

Site Status RECRUITING

Texas Oncology

The Woodlands, Texas, United States

Site Status RECRUITING

Texas Oncology

Tyler, Texas, United States

Site Status RECRUITING

Intermountain Medical Center

Murray, Utah, United States

Site Status RECRUITING

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status RECRUITING

Virginia Cancer Specialists, PC

Gainesville, Virginia, United States

Site Status RECRUITING

Prince of Wales Hospital

Randwick, New South Wales, Australia

Site Status RECRUITING

Icon Cancer Centre Wesley

Auchenflower, Queensland, Australia

Site Status RECRUITING

Cancer Research South Australia

Adelaide, South Australia, Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status RECRUITING

UZA

Edegem, , Belgium

Site Status RECRUITING

University Hospital Ghent

Ghent, , Belgium

Site Status RECRUITING

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Site Status RECRUITING

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, Canada

Site Status RECRUITING

McGill University Health Centre

Montreal, Quebec, Canada

Site Status RECRUITING

British of Columbia

Vancouver, , Canada

Site Status RECRUITING

Aalborg U.H

Aalborg, , Denmark

Site Status RECRUITING

Centre Hospitalier de Besançon

Besançon, , France

Site Status RECRUITING

Site Georges François Leclerc

Dijon, , France

Site Status RECRUITING

Centre Oscar Lambret

Lille, , France

Site Status RECRUITING

Centre Léon Bérard

Lyon, , France

Site Status RECRUITING

Institut Curie

Paris, , France

Site Status RECRUITING

Agaplesion Markus Krankenhaus

Frankfurt am Main, Hesse, Germany

Site Status RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Site Status RECRUITING

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Site Status RECRUITING

Kliniken Essen-Mitte

Essen, , Germany

Site Status RECRUITING

UMC Hamburg-Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Universitätsklinikum Mannheim GmbH

Mannheim, , Germany

Site Status RECRUITING

Universitätsfrauenkinik Ulm

Ulm, , Germany

Site Status RECRUITING

St. James's Hospital

Dublin, , Ireland

Site Status RECRUITING

Centro di Riferimento Oncologico (CRO)

Aviano, , Italy

Site Status RECRUITING

Spedali Civili

Brescia, , Italy

Site Status RECRUITING

AO Cannizzaro

Catania, , Italy

Site Status RECRUITING

San Raffaele Hospital

Milan, , Italy

Site Status RECRUITING

Humanitas San Pio X

Milan, , Italy

Site Status RECRUITING

European Institute of Oncology (IEO)

Milan, , Italy

Site Status RECRUITING

Istituto Nazionale dei Tumori

Milan, , Italy

Site Status RECRUITING

INT Napoli Hospital

Napoli, , Italy

Site Status RECRUITING

Istituto Oncologico Veneto (IOV)

Padua, , Italy

Site Status RECRUITING

IRCCS Gemelli

Roma, , Italy

Site Status RECRUITING

Istituti Fisioterapici Ospitalieri

Rome, , Italy

Site Status RECRUITING

S.C.D.U. Oncologia

Torino, , Italy

Site Status RECRUITING

The Mie University Hospital

Tsu, Mie-ken, Japan

Site Status RECRUITING

Tohoku University Hospital

Miyagi, , Japan

Site Status RECRUITING

Osaka Medical Center

Osaka, , Japan

Site Status RECRUITING

The Jikei University Hospital

Tokyo, , Japan

Site Status RECRUITING

Netherlands Cancer Insitute

Amsterdam, , Netherlands

Site Status RECRUITING

Radboud UMC

Nijmegen, , Netherlands

Site Status RECRUITING

Auckland City Hospital

Auckland, , New Zealand

Site Status RECRUITING

Białostockie Centrum Onkologii

Bialystok, , Poland

Site Status RECRUITING

Gdański Uniwersytet Medyczny

Gdansk, , Poland

Site Status RECRUITING

Siedleckie Centrum Onkologii

Siedlce, , Poland

Site Status RECRUITING

Seoul National University Bundang Hospital

Seongnam, , South Korea

Site Status RECRUITING

Yonsei University Severance Hospital

Seoul, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Gangnam Severance Hospital

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

Clínico Virgen de La Arrixaca

El Palmar, Murcia, Spain

Site Status RECRUITING

H. de Donostia

Donostia / San Sebastian, San Sebastian, Spain

Site Status RECRUITING

H. Vall d´ Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Reina Sofía

Córdoba, , Spain

Site Status RECRUITING

H.U. Ramón y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital Clínico Universitario de Santiago

Santiago de Compostela, , Spain

Site Status RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status RECRUITING

Greater Glasgow and Clyde (GGC)

Glasgow, Scotland, United Kingdom

Site Status RECRUITING

Cambridge University Hospital

Cambridge, , United Kingdom

Site Status RECRUITING

University of Edinburgh Cancer Research Centre

Edinburgh, , United Kingdom

Site Status RECRUITING

Hope Cancer Trials Centre

Leicester, , United Kingdom

Site Status RECRUITING

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Royal Marsden Hospital

London, , United Kingdom

Site Status RECRUITING

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status RECRUITING

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Belgium Canada Denmark France Germany Ireland Italy Japan Netherlands New Zealand Poland South Korea Spain United Kingdom

Central Contacts

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Verastem Call Center

Role: CONTACT

Phone: 781-292-4204

Email: [email protected]

Facility Contacts

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Sabrina Maham

Role: primary

Kathryn Allen

Role: primary

Jenny Lester

Role: primary

Johanna Han

Role: primary

Nathalie Halley

Role: primary

Lisa Baker

Role: primary

Christina Caruso

Role: primary

Antonio Ramirez Riderelli

Role: primary

Karla Hernandez-Cruz

Role: primary

Connor Hyde

Role: primary

Mary Jo Luser

Role: primary

Syed Ahsan

Role: primary

Michele Britto

Role: primary

Alex Yates

Role: primary

Faith Too

Role: primary

Role: backup

Elizabeth Linnik

Role: primary

Kayla McDonald

Role: primary

Linda Odibo

Role: primary

Kimberly Benczkowski

Role: primary

Rachel Grisham

Role: primary

Melani Terry

Role: primary

Jacqueline Ludwig

Role: primary

Jordyn Burks

Role: primary

Liz Barrett

Role: primary

Jeanne Scahffer

Role: primary

Jennifer Thompson

Role: primary

Ashley Douglas

Role: primary

Siobhan Guyach

Role: primary

Michelle Owens

Role: primary

Nori Sullivan

Role: primary

Konny Chan Fong

Role: primary

Mariana Gallardo, RN

Role: primary

Shannon Syring

Role: primary

Christina Genthon

Role: primary

Sandra Thornton

Role: backup

Shelly Maxfield

Role: primary

Stacy Howard

Role: primary

Zdravka (Ava) Daneva

Role: primary

Monica Cochrane

Role: primary

Kaye Kongrak

Role: primary

Amy Morrow

Role: primary

Vineet Kwatra, MD

Role: primary

Nicole Marsh

Role: primary

Jolanta Damas

Role: primary

Griet Wyers

Role: primary

Hannelore Denys, MD

Role: primary

Valerie Bowering

Role: primary

Nathalie Grenier

Role: primary

Phuong Nam Nathalie Nguyen

Role: primary

Fran Topp, RN

Role: primary

Mette Raaschou

Role: primary

Ophélie Sivignon

Role: primary

Kevin Le Berre

Role: primary

Clémence Goetz

Role: primary

Emilie Repetto, MD

Role: primary

Manuel Rodrigues, MD

Role: primary

Madeleine Modrow

Role: primary

Radoslav Chekerov, MD

Role: primary

Elena Ioana Braicu, MD

Role: backup

Christine Griebsch

Role: primary

Theresa Link

Role: backup

Anna Kasperek

Role: primary

Juliane Granzow

Role: primary

Manuela Reining

Role: primary

Wolfgang Janni

Role: primary

Lauren Murphy

Role: primary

Serena Corsetti

Role: primary

Eliana Bignotti

Role: primary

Francesca Salanitro

Role: primary

Alessandra Paggin

Role: backup

Silvia Pagani

Role: primary

Ilaria Sabatucci

Role: primary

Beatrice Rizzoli

Role: primary

Barbara Montesanto

Role: primary

Margherita Tambaro

Role: primary

Giulia Doria

Role: primary

Giulia Ponti

Role: primary

Agnese Provenziani

Role: primary

Giorgio Valabrega

Role: primary

Eiji Kondo

Role: primary

Shogo Shigeta

Role: primary

Satoe Fujiwara

Role: primary

Aikou Okamoto

Role: primary

Geesje Feingold - van Olst

Role: primary

Daphne van Dijk

Role: primary

Merina Mathews

Role: primary

Justyna Sławińska

Role: primary

Łukasz Jędrzejewski

Role: primary

Tomasz Milewski

Role: primary

Małgorzata Będkowska

Role: backup

Kidong Kim

Role: primary

Jung Yeon Lee

Role: primary

Sang Wun Kim

Role: backup

Geum Hee Na

Role: primary

Mina Jang

Role: primary

Jae-Hoon Kim

Role: backup

Jung Eun Park

Role: primary

Chel Hun Choi

Role: backup

Ana Puertes Boix

Role: primary

Cristina Maria Churruca Galaz

Role: primary

Olga Padros

Role: primary

Asuncion Aranda

Role: primary

Iluminada Hernandez Blazquez

Role: primary

Laura Gendra Maneiro

Role: primary

Paloma Campos Bañegil

Role: primary

Ros Glasspool, MD

Role: primary

Regulatory Team

Role: primary

Olga Demyanov

Role: primary

Joey Wood, MD

Role: primary

Christian Paul Medina

Role: primary

Shibani Nicum, MD

Role: backup

Kylie Fitch

Role: primary

Linzi Davies

Role: primary

Kylie Fitch

Role: primary

References

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Banerjee SN, Van Nieuwenhuysen E, Aghajanian C, D'Hondt V, Monk BJ, Clamp A, Prendergast E, Oaknin A, Ring K, Colombo N, Holloway RW, Rodrigues M, Chon HS, Gourley C, Santin AD, Thaker PH, Gennigens C, Newman G, Salinas E, Youssoufian H, Moore KN, Lustgarten S, O'Malley DM, Van Gorp T, Grisham RN. Efficacy and Safety of Avutometinib +/- Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201. J Clin Oncol. 2025 Sep;43(25):2782-2792. doi: 10.1200/JCO-25-00112. Epub 2025 Jul 11.

Reference Type DERIVED
PMID: 40644648 (View on PubMed)

Grisham R, Monk BJ, Van Nieuwenhuysen E, Moore KN, Fabbro M, O'Malley DM, Oaknin A, Thaker P, Oza AM, Colombo N, Gershenson D, Aghajanian CA, Choi CH, Lee YC, Mirza MR, Coleman RL, Cobb L, Harter P, Lustgarten S, Youssoufian H, Banerjee S. GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301: a phase 3, randomized trial evaluating avutometinib plus defactinib compared with investigator's choice of treatment in patients with recurrent low grade serous ovarian cancer. Int J Gynecol Cancer. 2025 Jan 6:ijgc-2024-005919. doi: 10.1136/ijgc-2024-005919. Online ahead of print.

Reference Type DERIVED
PMID: 39375168 (View on PubMed)

Other Identifiers

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GOG-3097

Identifier Type: OTHER

Identifier Source: secondary_id

ENGOT-ov81

Identifier Type: OTHER

Identifier Source: secondary_id

VS-6766-301

Identifier Type: -

Identifier Source: org_study_id