Pembrolizumab With Chemotherapy and MK-4830 for Treating Participants With Ovarian Cancer (MK-4830-002)

Ovarian Carcinoma Clinical Trial

Official title:

A Randomized, Phase 2 Study of Pembrolizumab And Chemotherapy With or Without MK-4830 as Neoadjuvant Treatment for High-Grade Serous Ovarian Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05446870
• Other study ID #: 4830-002
• Secondary ID: MK-4830-0022023-
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 25, 2022
• Est. completion date: December 26, 2024

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to evaluate in participants with high-grade serous ovarian cancer (HGSOC), whether the reduction from baseline in circulating tumor DNA (ctDNA) at Cycle 3 (ΔctDNA) is larger in participants receiving MK-4830 + pembrolizumab in combination with standard of care (SOC) therapy than in those receiving pembrolizumab + SOC therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: December 26, 2024
• Est. primary completion date: December 6, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Has histologically-confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV HGSOC, primary peritoneal cancer, or fallopian tube cancer.

• Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the neoadjuvant and adjuvant setting.

• Is a candidate for interval debulking surgery.

• Is able to provide archival tissue or newly obtained core, incisional, or excisional biopsy of a tumor lesion.

• Has adequate organ functions.

Exclusion Criteria:

• Has a non-HGSOC histology.

• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.

• Has received prior treatment for any stage of OC, including radiation or systemic anticancer therapy.

• Planned or has been administered intraperitoneal chemotherapy as first-line therapy.

• Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-immunoglobulin-like transcript 4 (ILT4), or anti-human leukocyte antigen (HLA)-G agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor.

• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.

• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.

• Has known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis.

• Has severe hypersensitivity to pembrolizumab, carboplatin, paclitaxel (or docetaxel, if applicable), Avastin or biosimilar (if using) and/or any of their excipients.

• Has an active autoimmune disease that has required systemic treatment in past 2 years.

• Has an active infection requiring systemic therapy.

• Has a known history of human immunodeficiency virus (HIV) infection.

• Has a known history of hepatitis B or known active hepatitis C virus infection.

• Has received colony-stimulating factors within 4 weeks prior to receiving study intervention on Day 1 of Cycle 1.

• Has had surgery <6 months prior to Screening to treat borderline ovarian tumors, early-stage OC, or early-stage fallopian tube cancer.

• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.

• Has current, clinically relevant bowel obstruction.

• Has a history of hemorrhage, hemoptysis, or active gastrointestinal (GI) bleeding within 6 months prior to randomization.

• Has uncontrolled hypertension.

• Has had an allogenic tissue/solid organ transplant.

• .Has either had major surgery within 3 weeks of randomization or has not recovered from any effects of any major surgery.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Ovarian Epithelial
• Ovarian Carcinoma
• Ovarian Neoplasms

Intervention

Biological:
• Pembrolizumab
200 mg by IV infusion on Day 1 of each 21-day cycle

Drug:
• Paclitaxel
175 mg/m^2 by IV infusion on Day 1 of each 21-day cycle
• Carboplatin
AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle

Biological:
• Avastin
According to local practice and at the choice of the investigator.
• MK-4830
800 mg by IV infusion on Day 1 of each 21-day cycle

Drug:
• Docetaxel
75 mg/m^2 by IV infusion on Day 1 of each 21-day cycle

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital-Oncology ( Site 1301)	Edegem	Antwerpen
Belgium	AZ Maria Middelares-IKG ( Site 1302)	Gent	Oost-Vlaanderen
Belgium	UZ Leuven ( Site 1300)	Leuven	Vlaams-Brabant
Canada	Centre Hospitalier de l'Université de Montréal ( Site 0300)	Montréal	Quebec
Canada	McGill University Health Centre ( Site 0301)	Montréal	Quebec
Chile	FALP ( Site 0905)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile-Centro del Cáncer ( Site 0900)	Santiago	Region M. De Santiago
Chile	James Lind Centro de Investigación del Cáncer ( Site 0903)	Temuco	Araucania
Chile	ONCOCENTRO APYS-ACEREY ( Site 0904)	Viña del Mar	Valparaiso
Israel	Rambam Health Care Campus-Gyneco-oncology unit ( Site 0602)	Haifa
Israel	Shaare Zedek Medical Center ( Site 0601)	Jerusalem
Israel	Sheba Medical Center-ONCOLOGY ( Site 0600)	Ramat Gan
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Chirurgia Ginecologica ( Site 050	Milan	Lombardia
Italy	Istituto Europeo di Oncologia IRCCS-Divisione di Ginecologia Oncologica ( Site 0501)	Milano
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale-S.C. Oncologia Sperimentale Uro-Genitale ( Site 0	Napoli	Campania
Italy	Fondazione Policlinico Universitario Agostino Gemelli-Ginecologia Oncologica ( Site 0502)	Roma	Lazio
Korea, Republic of	Seoul National University Hospital ( Site 0801)	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System-Gynecologic cancer center ( Site 0800)	Seoul
Poland	Uniwersyteckie Centrum Kliniczne-Klinika Ginekologii, Ginekologii Onkologicznej i Endokrynologii Gi	Gdansk	Pomorskie
Poland	Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej ( Site 0708)	Kielce	Swietokrzyskie
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu-Oddzial Ginekologii Onkologicznej ( Site 0709)	Poznan	Wielkopolskie
Poland	Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 0701)	Siedlce	Mazowieckie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Ginekologii Onkologicznej ( Sit	Warszawa	Mazowieckie
Singapore	National Cancer Centre Singapore ( Site 1501)	Singapore	Central Singapore
Singapore	National University Hospital ( Site 1502)	Singapore	South West
Spain	Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 1101)	Barcelona
Spain	Instituto Catalan de Oncologia - Hospital Duran i Reynals-Medical Oncology ( Site 1103)	Hospitalet	Barcelona
Spain	Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1104)	Madrid	Madrid, Comunidad De
Taiwan	Changhua Christian Hospital-Obstetrics and Gynecology ( Site 1203)	Changhua County	Changhua
Taiwan	Taichung Veterans General Hospital-GYNECOLOGY ( Site 1202)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 1201)	Tainan
Taiwan	Mackay Memorial Hospital ( Site 1204)	Taipei
Taiwan	National Taiwan University Hospital-Internal Medicine ( Site 1200)	Taipei
United States	University of Colorado Anschutz Medical Campus-Cancer Clinical Trials Office ( Site 0108)	Aurora	Colorado
United States	Roswell Park Cancer Institute ( Site 0106)	Buffalo	New York
United States	Northwestern Memorial Hospital ( Site 0104)	Chicago	Illinois
United States	Mayo Clinic in Florida ( Site 0101)	Jacksonville	Florida
United States	Miami Cancer Institute at Baptist Health, Inc. ( Site 0110)	Miami	Florida
United States	Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 0116)	Mineola	New York
United States	Rutgers Cancer Institute of New Jersey ( Site 0114)	New Brunswick	New Jersey
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone ( Site 0107)	New York	New York
United States	Memorial Sloan Kettering Cancer Center ( Site 0102)	New York	New York
United States	Washington University ( Site 0113)	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Center ( Site 0100)	Seattle	Washington
United States	Sanford Cancer Center-Gynecologic Oncology ( Site 0115)	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Chile,  Israel,  Italy,  Korea, Republic of,  Poland,  Singapore,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA)	Change from baseline in circulating tumor deoxyribonucleic acid (ctDNA).	Baseline and Week 7
Secondary	Change from Baseline in Neoadjuvant ctDNA	Change from baseline in neoadjuvant ctDNA.	Baseline and Week 7
Secondary	Pathological Complete Response (pCR) Rate	Percentage of participants with all surgical specimens collected during the interval debulking surgery that are microscopically negative for residual tumor by logistic regression modeling of pathological Complete Response (pCR).	Up to approximately 12 weeks
Secondary	Chemotherapy Response Score (CRS)	Percentage of participants with residual disease assessed by logistic regression modeling of chemotherapy response score (CRS). CRS is a 3-tiered scoring system (CRS 1-3) based on the pathological analysis of surgically removed omental masses, with CRS3 (complete or near-complete response) characterized by the lack of residual tumor cells in the omentum or presence of tumor foci up to 2 mm maximum size. A binary response of CRS3 (no residual disease) vs. non-CRS3 (residual disease) will be assessed.	Up to approximately 12 Weeks
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	An AE was any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug.	Up to approximately 40 Weeks
Secondary	Number of Participants Who Discontinued Study Treatment Due to an AE	An AE was any untoward medical occurrence in a participant administered study drug which does not necessarily have to have a causal relationship with the study drug.	Up to approximately 28 Weeks

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary