MK-7684A With or Without Other Anticancer Therapies in Participants With Selected Solid Tumors (MK-7684A-005) (KEYVIBE-005)

Hepatocellular Carcinoma Clinical Trial

Official title:

A Multicenter, Open-label, Phase 2 Basket Study of MK-7684A, a Co-formation of Vibostolimab (MK-7684) With Pembrolizumab (MK-3475), With or Without Other Anticancer Therapies in Participants With Selected Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05007106
• Other study ID #: 7684A-005
• Secondary ID: MK-7684A-005jRCT
• Status: Recruiting
• Phase: Phase 2
• Start date: September 16, 2021
• Est. completion date: February 22, 2027

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety, tolerability, and preliminary efficacy of pembrolizumab/vibostolimab co-formulation (MK-7684A) with or without other anticancer therapies in participants with selected advanced solid tumors. The primary hypothesis is that pembrolizumab/vibostolimab co-formulation is superior to pembrolizumab alone in terms of objective response rate or progression-free survival in participants with cervical cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 610
• Est. completion date: February 22, 2027
• Est. primary completion date: February 22, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• One of the following histologically or cytologically confirmed, advanced (unresectable or metastatic) solid tumors:

• Squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix

• Endometrial cancer

• Head and neck squamous cell carcinoma (HNSCC)

• Unresectable biliary adenocarcinoma (gallbladder or biliary tree [intrahepatic or extrahepatic] cholangiocarcinoma)

• Adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the gastroesophageal junction (GEJ).

• Triple-negative breast cancer (TNBC)

• Hepatocellular carcinoma (HCC)

• Urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra

• Ovarian cancer

• Gastric cancer

• Measurable disease per RECIST v1.1 as assessed by BICR or local site investigator.

• Adequately controlled blood pressure (BP) with or without antihypertensive medications.

• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART).

• Male participants must agree to follow contraceptive guidance.

• Female participants are not pregnant or breastfeeding, not a woman of child-bearing potential (WOCBP) or is a WOCBP and agrees to follow contraceptive guidance.

• Adequate organ function.

Exclusion Criteria:

• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.

• Prior therapy with anti-programmed cell-death (PD-1), anti-PD-L1, anti-PD-L2, or anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) agent.

• Prior systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation.

• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.

• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study medication.

• Active autoimmune disease that has required systemic treatment in past 2 years.

• Active infection requiring systemic therapy.

• Concurrent active hepatitis B and hepatitis C virus infection.

• History of allogenic tissue/solid organ transplant.

• Previous treatment with lenvatinib (for participants who will receive lenvatinib in their assigned treatment arm).

• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention.

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Cholangiocarcinoma
• Endometrial Neoplasms
• Esophageal Neoplasms
• Gallbladder Neoplasms
• Hepatocellular Carcinoma
• Neoplasms
• Ovarian Neoplasms
• Squamous Cell Carcinoma of Head and Neck
• Stomach Neoplasms
• Triple Negative Breast Neoplasms
• Urinary Bladder Neoplasms
• Uterine Cervical Neoplasms

Intervention

Biological:
• Pembrolizumab/Vibostolimab Co-Formulation
Pembrolizumab 200 mg plus vibostolimab 200 mg administered via IV infusion Q3W
• Pembrolizumab
Pembrolizumab 200 mg administered via IV infusion Q3W.

Drug:
• Lenvatinib
Lenvatinib 20 mg, 12 mg, or 8 mg (dependent on cancer type and body weight) administered via oral capsule QD
• 5-Fluorouracil
5-FU 800 mg/m^2/day administered via continuous IV infusion on each of days 1 to 5 Q3W for up to 35 cycles
• Cisplatin
Cisplatin administered via IV infusion
• Paclitaxel
Paclitaxel administered via IV infusion at investigator's choice of dose
• Gemcitabine
Gemcitabine administered via IV infusion on Day 1 and Day 8 of each 3-week cycle, until PD or unacceptable toxicity
• Carboplatin
Carboplatin administered via IV infusion at investigator's choice of dose and frequency
• Docetaxel
For participants who cannot receive paclitaxel due to hypersensitivity or adverse event (AE), docetaxel administered via IV infusion Q3W, Day 1 of each cycle for up to 5 cycles
• Bevacizumab
Bevacizumab (or biosimilars such as MVASI®, Zirabev®, Aybintio®, ALYMSYS®, Abevmy®, Onbevezy®, Vegzelma®) administered via IV infusion Q3W; Day 1 of each 3-week cycle for up to 15 cycles
• Capecitabine
Capecitabine administered via oral tablet twice daily on Days 1 to 14 of each cycle (Q3W) for up to 35 cycles
• Oxaliplatin
Oxaliplatin administered via IV infusion Q3W up to 35 cycles

Locations

Country	Name	City	State
Canada	Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 1051)	Kingston	Ontario
Canada	Princess Margaret Cancer Centre ( Site 1056)	Toronto	Ontario
Chile	Bradfordhill-Clinical Area ( Site 1402)	Santiago	Region M. De Santiago
Chile	FALP-UIDO ( Site 1401)	Santiago	Region M. De Santiago
Chile	Oncovida ( Site 1405)	Santiago	Region M. De Santiago
Chile	James Lind Centro de Investigación del Cáncer ( Site 1404)	Temuco	Araucania
Colombia	Clinica de la Costa S.A.S. ( Site 1421)	Barranquilla	Atlantico
Colombia	Instituto Nacional de Cancerología-Clinical Oncology ( Site 1425)	Bogotá	Cundinamarca
Colombia	Fundacion Colombiana de Cancerología Clinica Vida ( Site 1422)	Medellin	Antioquia
Colombia	Oncologos del Occidente ( Site 1424)	Pereira	Risaralda
Colombia	Fundación Cardiovascular de Colombia ( Site 1423)	Piedecuesta	Santander
France	Sainte Catherine Institut du Cancer Avignon Provence-Oncologie médicale ( Site 1156)	Avignon	Vaucluse
France	Centre Georges François Leclerc ( Site 1155)	Dijon	Cote-d Or
France	CENTRE LEON BERARD-Medical oncology ( Site 1151)	Lyon	Rhone-Alpes
France	Institut Régional du Cancer Montpellier ( Site 1157)	Montpellier	Herault
France	Institut Curie ( Site 1152)	Paris
France	Gustave Roussy-medicine departement ( Site 1153)	Villejuif	Paris
Germany	Charite Universitätsmedizin Berlin Campus Benjamin Franklin ( Site 1171)	Berlin
Germany	Universitaetsklinikum Duesseldorf-Gastroenterology, Hepatology and Infectiology ( Site 1172)	Düsseldorf	Nordrhein-Westfalen
Germany	Universitaetsklinikum Heidelberg-Nationales Centrum für Tumorerkrankungen ( Site 1180)	Heidelberg	Baden-Wurttemberg
Germany	Klinikum der Universität München Großhadern ( Site 1176)	München	Bayern
Germany	Universitaetsklinikum Tuebingen-Department of Internal Medicine VIII - Medical Oncology, ECTU, Pne	Tübingen	Baden-Wurttemberg
Israel	Rambam Health Care Campus-Oncology ( Site 1141)	Haifa
Israel	Hadassah Medical Center-Oncology ( Site 1142)	Jerusalem
Israel	Sheba Medical Center-ONCOLOGY ( Site 1144)	Ramat Gan
Israel	Sourasky Medical Center-Oncology ( Site 1143)	Tel Aviv
Italy	Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative (	Milano
Italy	Ospedale San Raffaele-Oncologia Medica ( Site 1135)	Milano	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale-S.C. Sperimentazioni Cliniche ( Site 1134)	Napoli
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Ginecologia Oncologica ( Site 1136)	Roma	Lazio
Japan	National Cancer Center Hospital East ( Site 1321)	Kashiwa	Chiba
Japan	Aichi Cancer Center Hospital ( Site 1324)	Nagoya	Aichi
Japan	Osaka International Cancer Institute ( Site 1323)	Osaka
Japan	National Cancer Center Hospital ( Site 1322)	Tokyo
Korea, Republic of	Asan Medical Center ( Site 1313)	Seoul
Korea, Republic of	Seoul National University Hospital-Internal Medicine ( Site 1312)	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1311)	Seoul
Netherlands	Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL) ( Site 1121)	Amsterdam	Noord-Holland
Netherlands	Erasmus Medisch Centrum-Medical Oncology ( Site 1122)	Rotterdam	Zuid-Holland
Poland	Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 1103)	Gdansk	Pomorskie
Poland	Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 1104)	Koszalin	Zachodniopomorskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 1101	Warszawa	Mazowieckie
Spain	Instituto Catalan de Oncologia - Hospital Duran i Reynals-Medical Oncology ( Site 1113)	Hospitalet	Barcelona
Spain	Clinica Universidad de Navarra-Medical Oncology ( Site 1118)	Madrid
Spain	Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1111)	Madrid	Madrid, Comunidad De
Spain	HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 1117)	Pozuelo de Alarcon	Madrid
Spain	HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO ( Site 1114)	Sevilla
Taiwan	NATIONAL CHENG-KUNG UNI. HOSP.-clinical trial center ( Site 1302)	Tainan
Taiwan	Mackay Memorial Hospital ( Site 1305)	Taipei
Taiwan	National Taiwan University Hospital-Oncology ( Site 1301)	Taipei
Taiwan	Chang Gung Medical Foundation-Linkou Branch ( Site 1304)	Taoyuan
Turkey	Baskent University Dr. Turgut Noyan Research and Training Center ( Site 1201)	Adana
Turkey	Ankara City Hospital-Medical Oncology ( Site 1202)	Ankara
Turkey	Hacettepe Universitesi-oncology hospital ( Site 1209)	Ankara
Turkey	Trakya University-Medical Oncology ( Site 1207)	Edirne
Turkey	Acibadem Universitesi Atakent Hastanesi ( Site 1208)	Istanbul
Turkey	TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1204)	Istanbul
Turkey	Istanbul Universitesi Cerrahpasa ( Site 1203)	Istanbul- Fatih	Istanbul
United States	Alaska Womens Cancer Care ( Site 1016)	Anchorage	Alaska
United States	Memorial Sloan Kettering - Basking Ridge ( Site 1023)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering- Commack ( Site 1021)	Commack	New York
United States	Karmanos Cancer Institute ( Site 1007)	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center ( Site 1001)	Duarte	California
United States	Memorial Sloan Kettering - Westchester ( Site 1020)	Harrison	New York
United States	Houston Methodist Hospital ( Site 1017)	Houston	Texas
United States	Memorial Sloan Kettering - Monmouth ( Site 1022)	Middletown	New Jersey
United States	Memorial Sloan Kettering - Bergen ( Site 1025)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center ( Site 1002)	New York	New York
United States	University of California, Irvine (UCI) Health - UC Irvine Me-Chao Family Comprehensive Cancer Cente	Orange	California
United States	Sanford Cancer Center-Gynecologic Oncology ( Site 1015)	Sioux Falls	South Dakota
United States	Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1024)	Tulsa	Oklahoma
United States	Memorial Sloan Kettering - Nassau ( Site 1026)	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Colombia,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)	ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented.	Up to approximately 2 years
Primary	Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.	Up to approximately 2 years
Primary	ORR per RECIST 1.1 as Assessed by Investigator in Participants with Selected Solid Tumors	ORR is defined as the percentage of participants who have a CR (Disappearance of all target lesions) or a PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by investigator based on RECIST 1.1 will be presented.	Up to approximately 2 years
Primary	PFS per RECIST 1.1 as Assessed by Investigator at 9 months	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD.	9 months
Primary	PFS per RECIST 1.1 as Assessed by Investigator at 12 months	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD.	12 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 5.5 years
Secondary	PFS per RECIST 1.1 as Assessed by Investigator	PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by investigator will be presented.	Up to approximately 2 years
Secondary	Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR	For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by BICR will be presented.	Up to approximately 2 years
Secondary	DOR per RECIST 1.1 as Assessed by Investigator	For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by investigator will be presented.	Up to approximately 2 years
Secondary	ORR per RECIST 1.1 as Assessed by Investigator	ORR is defined as the percentage of participants who have a CR (Disappearance of all target lesions) or a PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by investigator based on RECIST 1.1 will be presented.	Up to approximately 2 years
Secondary	PFS per RECIST 1.1 as Assessed by Investigator in Participants with Cervical Cancer	PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by investigator will be presented.	Up to approximately 2 years
Secondary	Change from Baseline in Global Health Status/Quality of Life Score (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 [EORTC QLQ-C30] Items 29 and 30)	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented.	Baseline and up to approximately 2 years
Secondary	Change from Baseline in Physical Functioning Score (EORTC QLQ-C30 Items 1-5)	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented.	Baseline and up to approximately 2 years
Secondary	Number of Participants Who Experienced One or More Adverse Events (AEs)	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 2 years
Secondary	Number of Participants Who Discontinued Study Intervention Due to an AE	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 2 years

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary