Clinical trial NCT04725188: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Non Small Cell Lung Cancer
Keywords: Programmed Cell Death Receptor 1 (PD-1)
Programmed Cell Death Receptor Ligand 1 (PD-L1)
Programmed Cell Death Receptor Ligand 2 (PD-L2)
PD-1
PDL1
PD-L1
PD-L2
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-01-26
Enrollment: 255
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment
timeFrame: Up to approximately 21 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Per RECIST 1.1 by BICR Assessment
timeFrame: Up to approximately 21 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 21 months
measure: Duration of Response (DOR) Per RECIST 1.1 by BICR Assessment
timeFrame: Up to approximately 21 months
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 21 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 18 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center ( Site 2522)
state: California
city: Peoria
country: United States
facility: Illinois Cancer Care ( Site 2534)
state: Illinois
city: Lexington
country: United States
facility: Baptist Health Lexington-Research ( Site 2502)
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland ( Site 2528)
state: Maryland
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic Hematology/Oncology ( Site 2511)
state: Mississippi
city: Saint Louis
country: United States
facility: Mercy Research - David C. Pratt Cancer Center ( Site 2532)
state: Missouri
city: Springfield
country: United States
facility: Mercy Research - Cancer and Hematology Center ( Site 2535)
state: Missouri
city: Bronx
country: United States
facility: Montefiore- Einstein Center for Cancer Care-Oncology ( Site 2509)
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 2526)
state: Ohio
city: Greenville
country: United States
facility: St Francis Cancer Center-Research Office ( Site 2531)
state: South Carolina
city: Berazategui
country: Argentina
facility: Centro de Oncología e Investigación de Buenos Aires ( Site 0008)
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Hospital Privado de Comunidad ( Site 0004)
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clínicas Mar del Plata ( Site 0002)
state: Buenos Aires
city: Rosario
country: Argentina
facility: Instituto de Oncología de Rosario ( Site 0003)
state: Santa Fe
city: Cordoba
country: Argentina
facility: Hospital Privado Universitario de Córdoba ( Site 0001)
city: La Rioja
country: Argentina
facility: Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0005)
city: Canberra
country: Australia
facility: Canberra Hospital ( Site 0104)
state: Australian Capital Territory
city: Southport
country: Australia
facility: Gold Coast University Hospital-Clinical Trials Service ( Site 0106)
state: Queensland
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital-Medical Oncology ( Site 0102)
state: Western Australia
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen-Department of Pneumology ( Site 0203)
state: Oberosterreich
city: Graz
country: Austria
facility: Medizinische Universität Graz ( Site 0201)
state: Steiermark
city: Wien
country: Austria
facility: Klinik Floridsdorf-Abteilung für Innere Medizin und Pneumologie ( Site 0204)
city: Mechelen
country: Belgium
facility: AZ Sint-Maarten, Campus Leopoldstraat 2 ( Site 0333)
state: Antwerpen
city: Brussels
country: Belgium
facility: UZ Brussel ( Site 0336)
state: Bruxelles-Capitale, Region De
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi-Oncology & Hematology ( Site 0337)
state: Hainaut
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis-Pulmonology & Thoracic Oncology ( Site 0338)
state: Limburg
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas ( Site 0334)
state: Oost-Vlaanderen
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceição ( Site 0403)
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 0400)
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
facility: Centro de Tratamento de Tumores Botafogo - CTTB-Pesquisa Clínica ( Site 0402)
city: Sao Paulo
country: Brazil
facility: Hospital Paulistano ( Site 0406)
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 0702)
state: Hovedstaden
city: Odense
country: Denmark
facility: Odense Universitetshospital ( Site 0700)
state: Syddanmark
city: Soenderborg
country: Denmark
facility: Sygehus Soenderjylland-Kraeftambulatoriet ( Site 0705)
state: Syddanmark
city: Tampere
country: Finland
facility: Tampereen yliopistollinen sairaala-Oncology ( Site 0906)
state: Pirkanmaa
city: Vaasa
country: Finland
facility: Vaasan Keskussairaala ( Site 0903)
state: Pohjanmaa
city: Oulu
country: Finland
facility: Oulun yliopistollinen sairaala ( Site 0902)
state: Pohjois-Pohjanmaa
city: Turku
country: Finland
facility: Turku University Hospital-The Department of Pulmonary Medicine ( Site 0905)
state: Varsinais-Suomi
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil (NHC) ( Site 1000)
state: Alsace
city: Bordeaux
country: France
facility: Institut Bergonié - Centre Régional de Lutte Contre Le Cance-Medical Oncology ( Site 1009)
state: Aquitaine
city: Caen
country: France
facility: Centre Hospitalier Universitaire de Caen - Hôpital Côte de Nacre ( Site 1006)
state: Calvados
city: Toulouse
country: France
facility: CHU de Toulouse - Hopital Larrey-service de pneumologie ( Site 1008)
state: Haute-Garonne
city: Beuvry
country: France
facility: Clinique Ambroise Paré ( Site 1007)
state: Pas-de-Calais
city: Le Mans
country: France
facility: Centre Hospitalier du Mans ( Site 1002)
state: Sarthe
city: Villejuif
country: France
facility: Gustave Roussy ( Site 1005)
state: Val-de-Marne
city: Toulon
country: France
facility: HIA Sainte Anne ( Site 1003)
state: Var
city: Avignon
country: France
facility: Centre Hospitalier d'Avignon-Service d'Oncologie médicale et d'hématologie clinique ( Site 1004)
state: Vaucluse
city: Ravensburg
country: Germany
facility: Onkologie Ravensburg ( Site 1104)
state: Baden-Wurttemberg
city: Immenstadt im Allgäu
country: Germany
facility: Klinikverbund Allgaeu gGmbH ( Site 1109)
state: Bayern
city: Wiesbaden
country: Germany
facility: Helios Dr. Horst Schmidt Kliniken ( Site 1108)
state: Hessen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn ( Site 1111)
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Helios Klinikum Emil von Behring Berlin-Zehlendorf ( Site 1106)
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center ( Site 1202)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology ( Site 1203)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center-Oncology ( Site 1206)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 1205)
city: Roma
country: Italy
facility: Azienda Ospedaliera S. Giovanni Addolorata-Oncologia Medica ( Site 1307)
state: Lazio
city: Naples
country: Italy
facility: Azienda Ospedaliera Dei Colli-U.O.C Pneumologia Oncologica DH PNL ONC ( Site 1308)
state: Napoli
city: Aviano
country: Italy
facility: CRO-IRCCS-medical oncology ( Site 1304)
state: Pordenone
city: Orbassano
country: Italy
facility: Azienda Sanitaria Ospedaliera S Luigi Gonzaga-Oncologia Polmonare ( Site 1300)
state: Torino
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi-SOD ONCOLOGIA MEDICA ( Site 1306)
state: Toscana
city: Milano
country: Italy
facility: Ospedale San Raffaele-Oncologia Medica ( Site 1305)
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Toracica ( Site 1301)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli-Medical Oncology ( Site 1303)
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital-Internal medicine ( Site 2004)
state: Chungbuk
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital ( Site 2003)
state: Kyonggi-do
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University Of Korea St. Vincent's Hospital-Medical Oncology ( Site 2005)
state: Kyonggi-do
city: Songpagu
country: Korea, Republic of
facility: Asan Medical Center-Oncology ( Site 2000)
state: Seoul
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail ( Site 1503)
state: Johor
city: Lembah Pantai
country: Malaysia
facility: University Malaya Medical Centre ( Site 1501)
state: Kuala Lumpur
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan ( Site 1500)
state: Pahang
city: Petaling Jaya
country: Malaysia
facility: Beacon Hospital Sdn Bhd ( Site 1504)
state: Selangor
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier
state: Mazowieckie
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED ( Site 1704)
state: Wielkopolskie
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov (
state: Leningradskaya Oblast
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1911)
state: Leningradskaya Oblast
city: Moscow
country: Russian Federation
facility: Hadassah Medical-Oncology department ( Site 1912)
state: Moskovskaya Oblast
city: Moscow
country: Russian Federation
facility: Moscow Clinical Research Center-Chemotherapy department ( Site 1910)
state: Moskva
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital of the Presidential Administrative Department ( Site 1902)
state: Moskva
city: Nizhniy Novgorod
country: Russian Federation
facility: Nizhegorodsky Regional Oncology Dispensary, Branch #2-chemotherapy ( Site 1909)
state: Nizhegorodskaya Oblast
city: Omsk
country: Russian Federation
facility: Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary ( Site 1908)
state: Omskaya Oblast
city: Saint Petersburg
country: Russian Federation
facility: N.N.Petrov Research Institute of Oncology-Department of Chemotherapy and Innovative Technologies ( S
state: Sankt-Peterburg
city: Saint-Petersburg
country: Russian Federation
facility: GBUZ LOKB-Oncology department #1 ( Site 1905)
state: Sankt-Peterburg
city: Barcelona
country: Spain
facility: HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Sit
state: Cataluna
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau-Oncología Médica ( Site 2102)
state: Cataluna
city: Madrid
country: Spain
facility: HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-ONCOLOGY ( Site 2101)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme-Departamento de Oncologia ( Site 2103)
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale Bellinzona e Valli ( Site 2203)
state: Ticino
city: Kaohsiung Niao Sung Dist
country: Taiwan
facility: Chang Gung Memorial Hospital at Kaohsiung ( Site 2303)
state: Kaohsiung
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital-Chest ( Site 2307)
city: Tainan
country: Taiwan
facility: NATIONAL CHENG-KUNG UNI. HOSP.-clinical trial center ( Site 2302)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital-Oncology ( Site 2304)
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital-Chest Medicine ( Site 2305)
city: Bangkok
country: Thailand
facility: Chulalongkorn University ( Site 2403)
state: Krung Thep Maha Nakhon
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital ( Site 2400)
state: Krung Thep Maha Nakhon
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: