Pembrolizumab/Vibostolimab Coformulation (MK-7684A) or Pembrolizumab/Vibostolimab Coformulation Plus Docetaxel Versus Docetaxel for Metastatic Non Small Cell Lung Cancer (NSCLC) With Progressive Disease After Platinum Doublet Chemotherapy and Immunotherapy (MK-7684A-002, KEYVIBE-002)

Metastatic Non Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 2, Multicenter, Randomized Study to Compare the Efficacy and Safety of MK-7684A or MK-7684A Plus Docetaxel Versus Docetaxel Monotherapy in the Treatment of Participants With Metastatic Non-small Cell Lung Cancer With Progressive Disease After Treatment With a Platinum Doublet Chemotherapy and Immunotherapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04725188
• Other study ID #: 7684A-002
• Secondary ID: MK-7684A-002KEYV
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 20, 2021
• Est. completion date: August 13, 2027

Study information

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

Clinical Trial Summary

The main purpose of this study is to compare pembrolizumab/vibostolimab coformulation (MK-7684A) plus docetaxel or pembrolizumab/vibostolimab coformulation to normal saline placebo plus docetaxel. Participants with metastatic non-small cell lung cancer (NSCLC) and progressive disease (PD) after platinum doublet chemotherapy and treatment with one prior anti- programmed cell death 1 (PD-1)/ programmed cell death ligand 1(PD-L1) monoclonal antibody (mAb). MK-7684A is a coformulation product of pembrolizumab/vibostolimab. The dual primary hypotheses of the study are pembrolizumab/vibostolimab coformulation plus docetaxel and pembrolizumab/vibostolimab coformulation is superior to normal saline placebo plus docetaxel with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

Description:

Participants may receive additional 17 cycles of pembrolizumab/vibostolimab (each cycle length = 21 days) for an additional 1 year of treatment as second course phase at investigator's discretion.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 255
• Est. completion date: August 13, 2027
• Est. primary completion date: January 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)

• Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or reactive oxygen species (ROS) 1 directed therapy is not indicated as primary therapy

• Has progressive disease (PD) on treatment with one prior anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies

• Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall course of treatment

• Has PD as determined by the investigator after platinum doublet chemotherapy for metastatic disease

• Has measurable disease defined as at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI), based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

• Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated

• Has a life expectancy of at least 3 months

• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days prior to randomization

• Male participants randomized to docetaxel are eligible to participant if they agree to refrain from donating sperm, and either 1) be abstinent from heterosexual intercourse; or 2) must agree to follow contraceptive guidance as per study protocol unless confirmed to be azoospermic during the intervention period and for at least 180 days after the last dose of docetaxel

• Female participants must be not pregnant, not breastfeeding, and not be a woman of child-bearing potential (WOCBP). A WOCBP is eligible is she agrees to either use contraception, or be abstinent from heterosexual intercourse during the intervention period and for =120 days after the last dose of study intervention. If a WOCBP is randomized to docetaxel, she agrees not to donate eggs and either uses contraception or be abstinent from heterosexual intercourse during the treatment period and for =180 days after the last dose of docetaxel

• Has adequate organ function

Exclusion Criteria:

• Has known active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis

• Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy

• Has received docetaxel as monotherapy or in combination with other therapies

• Has received previous treatment with another agent targeting the T-cell immunoreceptor with immunoglobulin [Ig] and immunoreceptor tyrosine-based inhibitory motif [ITIM] domains (TIGIT) pathway

• Has received radiotherapy within 2 weeks of start of study intervention. One week washout is permitted for palliative radiation to non-CNS disease

• 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 severe hypersensitivity (=Grade 3) to docetaxel or pembrolizumab/vibostolimab coformulation and/or any of its excipients

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

• Has a 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 intervention

• Has interstitial lung disease, or history of pneumonitis requiring steroids for treatment

• Has known history of active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C

• Has had an allogenic tissue/solid organ transplant

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Disease Progression
• Lung Neoplasms
• Metastatic Non Small Cell Lung Cancer

Intervention

Biological:
• Pembrolizumab/Vibostolimab coformuation
Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion Q3W up to approximately 2 years.

Drug:
• Docetaxel
Docetaxel 75 mg^m2 IV infusion Q3W until discontinuation due to progressive disease or unacceptable toxicity. Docetaxel will serve as part of an experimental treatment in Arm 1, and as an active comparator in Arm 3.
• Placebo
Normal saline IV infusion Q3W up to approximately 2 years

Locations

Country	Name	City	State
Argentina	Centro de Oncología e Investigación de Buenos Aires ( Site 0008)	Berazategui	Buenos Aires
Argentina	Hospital Privado Universitario de Córdoba ( Site 0001)	Cordoba
Argentina	Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0005)	La Rioja
Argentina	Hospital Privado de Comunidad ( Site 0004)	Mar del Plata	Buenos Aires
Argentina	Instituto de Investigaciones Clínicas Mar del Plata ( Site 0002)	Mar del Plata	Buenos Aires
Argentina	Instituto de Oncología de Rosario ( Site 0003)	Rosario	Santa Fe
Australia	Canberra Hospital ( Site 0104)	Canberra	Australian Capital Territory
Australia	Fiona Stanley Hospital-Medical Oncology ( Site 0102)	Murdoch	Western Australia
Australia	Gold Coast University Hospital-Clinical Trials Service ( Site 0106)	Southport	Queensland
Austria	Medizinische Universität Graz ( Site 0201)	Graz	Steiermark
Austria	Ordensklinikum Linz GmbH Elisabethinen-Department of Pneumology ( Site 0203)	Linz	Oberosterreich
Austria	Klinik Floridsdorf-Abteilung für Innere Medizin und Pneumologie ( Site 0204)	Wien
Belgium	UZ Brussel ( Site 0336)	Brussels	Bruxelles-Capitale, Region De
Belgium	Grand Hôpital de Charleroi-Oncology & Hematology ( Site 0337)	Charleroi	Hainaut
Belgium	Jessa Ziekenhuis-Pulmonology & Thoracic Oncology ( Site 0338)	Hasselt	Limburg
Belgium	AZ Sint-Maarten, Campus Leopoldstraat 2 ( Site 0333)	Mechelen	Antwerpen
Belgium	AZ Nikolaas ( Site 0334)	Sint-Niklaas	Oost-Vlaanderen
Brazil	Hospital Nossa Senhora da Conceição ( Site 0403)	Porto Alegre	Rio Grande Do Sul
Brazil	Centro de Tratamento de Tumores Botafogo - CTTB-Pesquisa Clínica ( Site 0402)	Rio de Janeiro
Brazil	Hospital Paulistano ( Site 0406)	Sao Paulo
Brazil	ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 0400)	São Paulo	Sao Paulo
Denmark	Rigshospitalet ( Site 0702)	Copenhagen	Hovedstaden
Denmark	Odense Universitetshospital ( Site 0700)	Odense	Syddanmark
Denmark	Sygehus Soenderjylland-Kraeftambulatoriet ( Site 0705)	Soenderborg	Syddanmark
Finland	Oulun yliopistollinen sairaala ( Site 0902)	Oulu	Pohjois-Pohjanmaa
Finland	Tampereen yliopistollinen sairaala-Oncology ( Site 0906)	Tampere	Pirkanmaa
Finland	Turku University Hospital-The Department of Pulmonary Medicine ( Site 0905)	Turku	Varsinais-Suomi
Finland	Vaasan Keskussairaala ( Site 0903)	Vaasa	Pohjanmaa
France	Centre Hospitalier d'Avignon-Service d'Oncologie médicale et d'hématologie clinique ( Site 1004)	Avignon	Vaucluse
France	Clinique Ambroise Paré ( Site 1007)	Beuvry	Pas-de-Calais
France	Institut Bergonié - Centre Régional de Lutte Contre Le Cance-Medical Oncology ( Site 1009)	Bordeaux	Aquitaine
France	Centre Hospitalier Universitaire de Caen - Hôpital Côte de Nacre ( Site 1006)	Caen	Calvados
France	Centre Hospitalier du Mans ( Site 1002)	Le Mans	Sarthe
France	Nouvel Hôpital Civil (NHC) ( Site 1000)	Strasbourg	Alsace
France	HIA Sainte Anne ( Site 1003)	Toulon	Var
France	CHU de Toulouse - Hopital Larrey-service de pneumologie ( Site 1008)	Toulouse	Haute-Garonne
France	Gustave Roussy ( Site 1005)	Villejuif	Val-de-Marne
Germany	Helios Klinikum Emil von Behring Berlin-Zehlendorf ( Site 1106)	Berlin
Germany	Universitätsklinikum Bonn ( Site 1111)	Bonn	Nordrhein-Westfalen
Germany	Klinikverbund Allgaeu gGmbH ( Site 1109)	Immenstadt im Allgäu	Bayern
Germany	Onkologie Ravensburg ( Site 1104)	Ravensburg	Baden-Wurttemberg
Germany	Helios Dr. Horst Schmidt Kliniken ( Site 1108)	Wiesbaden	Hessen
Israel	Soroka Medical Center ( Site 1202)	Be'er Sheva
Israel	Rambam Health Care Campus-Oncology ( Site 1203)	Haifa
Israel	Shaare Zedek Medical Center-Oncology ( Site 1206)	Jerusalem
Israel	Sourasky Medical Center ( Site 1205)	Tel Aviv
Italy	CRO-IRCCS-medical oncology ( Site 1304)	Aviano	Pordenone
Italy	Azienda Ospedaliera Universitaria Careggi-SOD ONCOLOGIA MEDICA ( Site 1306)	Firenze	Toscana
Italy	Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Toracica ( Site 1301)	Milano
Italy	Ospedale San Raffaele-Oncologia Medica ( Site 1305)	Milano
Italy	Azienda Ospedaliera Dei Colli-U.O.C Pneumologia Oncologica DH PNL ONC ( Site 1308)	Naples	Napoli
Italy	Azienda Sanitaria Ospedaliera S Luigi Gonzaga-Oncologia Polmonare ( Site 1300)	Orbassano	Torino
Italy	Azienda Ospedaliera S. Giovanni Addolorata-Oncologia Medica ( Site 1307)	Roma	Lazio
Italy	Fondazione Policlinico Universitario Agostino Gemelli-Medical Oncology ( Site 1303)	Roma
Korea, Republic of	Chungbuk National University Hospital-Internal medicine ( Site 2004)	Cheongju-si	Chungbuk
Korea, Republic of	Seoul National University Bundang Hospital ( Site 2003)	Seongnam	Kyonggi-do
Korea, Republic of	Asan Medical Center-Oncology ( Site 2000)	Songpagu	Seoul
Korea, Republic of	The Catholic University Of Korea St. Vincent's Hospital-Medical Oncology ( Site 2005)	Suwon-si	Kyonggi-do
Malaysia	Hospital Sultan Ismail ( Site 1503)	Johor Bahru	Johor
Malaysia	Hospital Tengku Ampuan Afzan ( Site 1500)	Kuantan	Pahang
Malaysia	University Malaya Medical Centre ( Site 1501)	Lembah Pantai	Kuala Lumpur
Malaysia	Beacon Hospital Sdn Bhd ( Site 1504)	Petaling Jaya	Selangor
Poland	Przychodnia Lekarska KOMED ( Site 1704)	Konin	Wielkopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier	Warszawa	Mazowieckie
Russian Federation	Central Clinical Hospital of the Presidential Administrative Department ( Site 1902)	Moscow	Moskva
Russian Federation	Hadassah Medical-Oncology department ( Site 1912)	Moscow	Moskovskaya Oblast
Russian Federation	Moscow Clinical Research Center-Chemotherapy department ( Site 1910)	Moscow	Moskva
Russian Federation	Nizhegorodsky Regional Oncology Dispensary, Branch #2-chemotherapy ( Site 1909)	Nizhniy Novgorod	Nizhegorodskaya Oblast
Russian Federation	Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary ( Site 1908)	Omsk	Omskaya Oblast
Russian Federation	N.N.Petrov Research Institute of Oncology-Department of Chemotherapy and Innovative Technologies ( S	Saint Petersburg	Sankt-Peterburg
Russian Federation	Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov (	Saint Petersburg	Leningradskaya Oblast
Russian Federation	Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1911)	Saint Petersburg	Leningradskaya Oblast
Russian Federation	GBUZ LOKB-Oncology department #1 ( Site 1905)	Saint-Petersburg	Sankt-Peterburg
Spain	HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Sit	Barcelona	Cataluna
Spain	Hospital de la Santa Creu i Sant Pau-Oncología Médica ( Site 2102)	Barcelona	Cataluna
Spain	HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-ONCOLOGY ( Site 2101)	Madrid
Spain	Hospital Universitario Virgen de Valme-Departamento de Oncologia ( Site 2103)	Sevilla
Switzerland	Ospedale Regionale Bellinzona e Valli ( Site 2203)	Bellinzona	Ticino
Taiwan	Chang Gung Memorial Hospital at Kaohsiung ( Site 2303)	Kaohsiung Niao Sung Dist	Kaohsiung
Taiwan	Taichung Veterans General Hospital-Chest ( Site 2307)	Taichung
Taiwan	NATIONAL CHENG-KUNG UNI. HOSP.-clinical trial center ( Site 2302)	Tainan
Taiwan	Mackay Memorial Hospital-Chest Medicine ( Site 2305)	Taipei
Taiwan	National Taiwan University Hospital-Oncology ( Site 2304)	Taipei
Thailand	Chulalongkorn University ( Site 2403)	Bangkok	Krung Thep Maha Nakhon
Thailand	Faculty of Medicine Siriraj Hospital ( Site 2400)	Bangkok	Krung Thep Maha Nakhon
United States	University of Maryland ( Site 2528)	Baltimore	Maryland
United States	Montefiore- Einstein Center for Cancer Care-Oncology ( Site 2509)	Bronx	New York
United States	University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 2526)	Cincinnati	Ohio
United States	St Francis Cancer Center-Research Office ( Site 2531)	Greenville	South Carolina
United States	Hattiesburg Clinic Hematology/Oncology ( Site 2511)	Hattiesburg	Mississippi
United States	Baptist Health Lexington-Research ( Site 2502)	Lexington	Kentucky
United States	Cedars-Sinai Medical Center ( Site 2522)	Los Angeles	California
United States	Illinois Cancer Care ( Site 2534)	Peoria	Illinois
United States	Mercy Research - David C. Pratt Cancer Center ( Site 2532)	Saint Louis	Missouri
United States	Mercy Research - Cancer and Hematology Center ( Site 2535)	Springfield	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Denmark,  Finland,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Poland,  Russian Federation,  Spain,  Switzerland,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment	PFS is defined as the time from randomization to the first documented disease progression (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 is presented.	Up to approximately 21 months
Secondary	Objective Response Rate (ORR) Per RECIST 1.1 by BICR Assessment	ORR is defined as the percentage of participants who have a confirmed 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 BICR based on RECIST 1.1 is presented.	Up to approximately 21 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to the date of death due to any cause.	Up to approximately 21 months
Secondary	Duration of Response (DOR) Per RECIST 1.1 by BICR Assessment	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 disease progression (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 was also considered PD. The DOR as assessed by BICR is presented.	Up to approximately 21 months
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Number of participants who experienced an AE is reported.	Up to approximately 21 months
Secondary	Number of Participants Who Discontinued Study Treatment Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Number of participants who discontinued study treatment due to an AE is reported.	Up to approximately 18 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary