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)
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1: Pembrolizumab/Vibostolimab coformulation + Docetaxel Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous IV infusion once every 3 weeks (Q3W) for up to 35 cycles up to approximately 2 years plus docetaxel 75 mg/m^2 IV infusion Q3W until discontinuation due to progressive disease or unacceptable toxicity. |
Biological: Pembrolizumab/Vibostolimab coformuation
Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion Q3W up to approximately 2 years.
Other Names:
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.
Other Names:
|
| Experimental: Arm 2: Pembrolizumab/Vibostolimab coformulation Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via IV infusion Q3W for up to 35 cycles up to approximately 2 years. |
Biological: Pembrolizumab/Vibostolimab coformuation
Pembrolizumab 200 mg + vibostolimab 200 mg/20 mL vial IV infusion Q3W up to approximately 2 years.
Other Names:
|
| Active Comparator: Arm 3: Placebo + Docetaxel Participants receive normal saline IV infusion, Q3W for up to 35 cycles up to approximately 2 years plus Docetaxel 75 mg/m^2 IV infusion Q3W until discontinuation due to progressive disease or unacceptable toxicity. |
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.
Other Names:
Drug: Placebo
Normal saline IV infusion Q3W up to approximately 2 years
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment [Up to approximately 27 months]
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 will be presented
Secondary Outcome Measures
- Objective Response (OR) per RECIST 1.1 by BICR Assessment [Up to approximately 27 months]
OR is defined as 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 will be presented.
- Overall Survival (OS) [Up to approximately 77 months]
OS is defined as the time from randomization to the date of death due to any cause.
- Duration of Response (DOR) per RECIST 1.1 by BICR Assessment [Up to approximately 77 months]
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 will be presented.
- Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 77 months]
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 experience an AE will be reported.
- Number of Participants Who Discontinued Study Treatment Due to an AE [Up to approximately 37 months]
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 discontinue study treatment due to an AE will be reported.
Eligibility Criteria
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
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Has PD as determined by the investigator after platinum doublet chemotherapy for metastatic disease
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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)
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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
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Has a life expectancy of at least 3 months
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Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days prior to randomization
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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
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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
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Has received docetaxel as monotherapy or in combination with other therapies
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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
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Has received radiotherapy within 2 weeks of start of study intervention. One week washout is permitted for palliative radiation to non-CNS disease
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Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
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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
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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
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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
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Has interstitial lung disease, or history of pneumonitis requiring steroids for treatment
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Has known history of active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C
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Has had an allogenic tissue/solid organ transplant
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Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cedars-Sinai Medical Center ( Site 2522) | Los Angeles | California | United States | 90048 |
| 2 | Illinois Cancer Care ( Site 2534) | Peoria | Illinois | United States | 61615 |
| 3 | Baptist Health Lexington-Research ( Site 2502) | Lexington | Kentucky | United States | 40503 |
| 4 | University of Maryland ( Site 2528) | Baltimore | Maryland | United States | 21201 |
| 5 | Hattiesburg Clinic Hematology/Oncology ( Site 2511) | Hattiesburg | Mississippi | United States | 39401 |
| 6 | Mercy Research - David C. Pratt Cancer Center ( Site 2532) | Saint Louis | Missouri | United States | 63109 |
| 7 | Mercy Research - Cancer and Hematology Center ( Site 2535) | Springfield | Missouri | United States | 65804 |
| 8 | Montefiore- Einstein Center for Cancer Care-Oncology ( Site 2509) | Bronx | New York | United States | 10461 |
| 9 | University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 2526) | Cincinnati | Ohio | United States | 45219 |
| 10 | St Francis Cancer Center-Research Office ( Site 2531) | Greenville | South Carolina | United States | 29607 |
| 11 | Centro de Oncología e Investigación de Buenos Aires ( Site 0008) | Berazategui | Buenos Aires | Argentina | B1884BBF |
| 12 | Hospital Privado de Comunidad ( Site 0004) | Mar del Plata | Buenos Aires | Argentina | 7600 |
| 13 | Instituto de Investigaciones Clínicas Mar del Plata ( Site 0002) | Mar del Plata | Buenos Aires | Argentina | 7600 |
| 14 | Instituto de Oncología de Rosario ( Site 0003) | Rosario | Santa Fe | Argentina | S2000KZE |
| 15 | Hospital Privado Universitario de Córdoba ( Site 0001) | Cordoba | Argentina | 5016 | |
| 16 | Fundación CORI para la Investigación y Prevención del Cáncer ( Site 0005) | La Rioja | Argentina | F5300COE | |
| 17 | Canberra Hospital ( Site 0104) | Canberra | Australian Capital Territory | Australia | 2605 |
| 18 | Gold Coast University Hospital-Clinical Trials Service ( Site 0106) | Southport | Queensland | Australia | 4215 |
| 19 | Fiona Stanley Hospital-Medical Oncology ( Site 0102) | Murdoch | Western Australia | Australia | 6150 |
| 20 | Ordensklinikum Linz GmbH Elisabethinen-Department of Pneumology ( Site 0203) | Linz | Oberosterreich | Austria | 4020 |
| 21 | Medizinische Universität Graz ( Site 0201) | Graz | Steiermark | Austria | 8036 |
| 22 | Klinik Floridsdorf-Abteilung für Innere Medizin und Pneumologie ( Site 0204) | Wien | Austria | 1210 | |
| 23 | AZ Sint-Maarten, Campus Leopoldstraat 2 ( Site 0333) | Mechelen | Antwerpen | Belgium | 2800 |
| 24 | UZ Brussel ( Site 0336) | Brussels | Bruxelles-Capitale, Region De | Belgium | 1090 |
| 25 | Grand Hôpital de Charleroi-Oncology & Hematology ( Site 0337) | Charleroi | Hainaut | Belgium | 6000 |
| 26 | Jessa Ziekenhuis-Pulmonology & Thoracic Oncology ( Site 0338) | Hasselt | Limburg | Belgium | 3500 |
| 27 | AZ Nikolaas ( Site 0334) | Sint-Niklaas | Oost-Vlaanderen | Belgium | 1932 |
| 28 | Hospital Nossa Senhora da Conceição ( Site 0403) | Porto Alegre | Rio Grande Do Sul | Brazil | 91350-200 |
| 29 | ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 0400) | São Paulo | Sao Paulo | Brazil | 01246-000 |
| 30 | Centro de Tratamento de Tumores Botafogo - CTTB-Pesquisa Clínica ( Site 0402) | Rio de Janeiro | Brazil | 22250-905 | |
| 31 | Hospital Paulistano ( Site 0406) | Sao Paulo | Brazil | 01321-000 | |
| 32 | Rigshospitalet ( Site 0702) | Copenhagen | Hovedstaden | Denmark | 2100 |
| 33 | Odense Universitetshospital ( Site 0700) | Odense | Syddanmark | Denmark | 5000 |
| 34 | Sygehus Soenderjylland-Kraeftambulatoriet ( Site 0705) | Soenderborg | Syddanmark | Denmark | 6400 |
| 35 | Tampereen yliopistollinen sairaala-Oncology ( Site 0906) | Tampere | Pirkanmaa | Finland | 33520 |
| 36 | Vaasan Keskussairaala ( Site 0903) | Vaasa | Pohjanmaa | Finland | 65130 |
| 37 | Oulun yliopistollinen sairaala ( Site 0902) | Oulu | Pohjois-Pohjanmaa | Finland | 90220 |
| 38 | Turku University Hospital-The Department of Pulmonary Medicine ( Site 0905) | Turku | Varsinais-Suomi | Finland | 20520 |
| 39 | Nouvel Hôpital Civil (NHC) ( Site 1000) | Strasbourg | Alsace | France | 67000 |
| 40 | Institut Bergonié - Centre Régional de Lutte Contre Le Cance-Medical Oncology ( Site 1009) | Bordeaux | Aquitaine | France | 33000 |
| 41 | Centre Hospitalier Universitaire de Caen - Hôpital Côte de Nacre ( Site 1006) | Caen | Calvados | France | 14033 |
| 42 | CHU de Toulouse - Hopital Larrey-service de pneumologie ( Site 1008) | Toulouse | Haute-Garonne | France | 31059 |
| 43 | Clinique Ambroise Paré ( Site 1007) | Beuvry | Pas-de-Calais | France | 62660 |
| 44 | Centre Hospitalier du Mans ( Site 1002) | Le Mans | Sarthe | France | 72037 |
| 45 | Gustave Roussy ( Site 1005) | Villejuif | Val-de-Marne | France | 94800 |
| 46 | HIA Sainte Anne ( Site 1003) | Toulon | Var | France | 83800 Cedex 9 |
| 47 | Centre Hospitalier d'Avignon-Service d'Oncologie médicale et d'hématologie clinique ( Site 1004) | Avignon | Vaucluse | France | 84000 |
| 48 | Onkologie Ravensburg ( Site 1104) | Ravensburg | Baden-Wurttemberg | Germany | 88212 |
| 49 | Klinikverbund Allgaeu gGmbH ( Site 1109) | Immenstadt im Allgäu | Bayern | Germany | 87509 |
| 50 | Helios Dr. Horst Schmidt Kliniken ( Site 1108) | Wiesbaden | Hessen | Germany | 65199 |
| 51 | Universitätsklinikum Bonn ( Site 1111) | Bonn | Nordrhein-Westfalen | Germany | 53127 |
| 52 | Helios Klinikum Emil von Behring Berlin-Zehlendorf ( Site 1106) | Berlin | Germany | 14165 | |
| 53 | Soroka Medical Center ( Site 1202) | Be'er Sheva | Israel | 8410101 | |
| 54 | Rambam Health Care Campus-Oncology ( Site 1203) | Haifa | Israel | 3109601 | |
| 55 | Shaare Zedek Medical Center-Oncology ( Site 1206) | Jerusalem | Israel | 9103102 | |
| 56 | Sourasky Medical Center ( Site 1205) | Tel Aviv | Israel | 6423906 | |
| 57 | Azienda Ospedaliera S. Giovanni Addolorata-Oncologia Medica ( Site 1307) | Roma | Lazio | Italy | 00184 |
| 58 | Azienda Ospedaliera Dei Colli-U.O.C Pneumologia Oncologica DH PNL ONC ( Site 1308) | Naples | Napoli | Italy | 80131 |
| 59 | CRO-IRCCS-medical oncology ( Site 1304) | Aviano | Pordenone | Italy | 33081 |
| 60 | Azienda Sanitaria Ospedaliera S Luigi Gonzaga-Oncologia Polmonare ( Site 1300) | Orbassano | Torino | Italy | 10043 |
| 61 | Azienda Ospedaliera Universitaria Careggi-SOD ONCOLOGIA MEDICA ( Site 1306) | Firenze | Toscana | Italy | 50134 |
| 62 | Ospedale San Raffaele-Oncologia Medica ( Site 1305) | Milano | Italy | 20132 | |
| 63 | Istituto Europeo di Oncologia IRCCS-Divisione di Oncologia Toracica ( Site 1301) | Milano | Italy | 20141 | |
| 64 | Fondazione Policlinico Universitario Agostino Gemelli-Medical Oncology ( Site 1303) | Roma | Italy | 00168 | |
| 65 | Chungbuk National University Hospital-Internal medicine ( Site 2004) | Cheongju-si | Chungbuk | Korea, Republic of | 28644 |
| 66 | Seoul National University Bundang Hospital ( Site 2003) | Seongnam | Kyonggi-do | Korea, Republic of | 13620 |
| 67 | The Catholic University Of Korea St. Vincent's Hospital-Medical Oncology ( Site 2005) | Suwon-si | Kyonggi-do | Korea, Republic of | 16247 |
| 68 | Asan Medical Center-Oncology ( Site 2000) | Songpagu | Seoul | Korea, Republic of | 05505 |
| 69 | Hospital Sultan Ismail ( Site 1503) | Johor Bahru | Johor | Malaysia | 81100 |
| 70 | University Malaya Medical Centre ( Site 1501) | Lembah Pantai | Kuala Lumpur | Malaysia | 59100 |
| 71 | Hospital Tengku Ampuan Afzan ( Site 1500) | Kuantan | Pahang | Malaysia | 25100 |
| 72 | Beacon Hospital Sdn Bhd ( Site 1504) | Petaling Jaya | Selangor | Malaysia | 46050 |
| 73 | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier | Warszawa | Mazowieckie | Poland | 02-781 |
| 74 | Przychodnia Lekarska KOMED ( Site 1704) | Konin | Wielkopolskie | Poland | 62-500 |
| 75 | Saint Petersburg State University-Clinic of advanced medical technologies n. a. Nicolay I. Pirogov ( | Saint Petersburg | Leningradskaya Oblast | Russian Federation | 190020 |
| 76 | Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1911) | Saint Petersburg | Leningradskaya Oblast | Russian Federation | 198255 |
| 77 | Hadassah Medical-Oncology department ( Site 1912) | Moscow | Moskovskaya Oblast | Russian Federation | 121205 |
| 78 | Moscow Clinical Research Center-Chemotherapy department ( Site 1910) | Moscow | Moskva | Russian Federation | 111123 |
| 79 | Central Clinical Hospital of the Presidential Administrative Department ( Site 1902) | Moscow | Moskva | Russian Federation | 121359 |
| 80 | Nizhegorodsky Regional Oncology Dispensary, Branch #2-chemotherapy ( Site 1909) | Nizhniy Novgorod | Nizhegorodskaya Oblast | Russian Federation | 603081 |
| 81 | Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary ( Site 1908) | Omsk | Omskaya Oblast | Russian Federation | 644013 |
| 82 | N.N.Petrov Research Institute of Oncology-Department of Chemotherapy and Innovative Technologies ( S | Saint Petersburg | Sankt-Peterburg | Russian Federation | 197758 |
| 83 | GBUZ LOKB-Oncology department #1 ( Site 1905) | Saint-Petersburg | Sankt-Peterburg | Russian Federation | 194291 |
| 84 | HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Sit | Barcelona | Cataluna | Spain | 08036 |
| 85 | Hospital de la Santa Creu i Sant Pau-Oncología Médica ( Site 2102) | Barcelona | Cataluna | Spain | 08041 |
| 86 | HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-ONCOLOGY ( Site 2101) | Madrid | Spain | 28009 | |
| 87 | Hospital Universitario Virgen de Valme-Departamento de Oncologia ( Site 2103) | Sevilla | Spain | 41014 | |
| 88 | Ospedale Regionale Bellinzona e Valli ( Site 2203) | Bellinzona | Ticino | Switzerland | 6500 |
| 89 | Chang Gung Memorial Hospital at Kaohsiung ( Site 2303) | Kaohsiung Niao Sung Dist | Kaohsiung | Taiwan | 83301 |
| 90 | Taichung Veterans General Hospital-Chest ( Site 2307) | Taichung | Taiwan | 40705 | |
| 91 | NATIONAL CHENG-KUNG UNI. HOSP.-clinical trial center ( Site 2302) | Tainan | Taiwan | 704 | |
| 92 | National Taiwan University Hospital-Oncology ( Site 2304) | Taipei | Taiwan | 10002 | |
| 93 | Mackay Memorial Hospital-Chest Medicine ( Site 2305) | Taipei | Taiwan | 10449 | |
| 94 | Chulalongkorn University ( Site 2403) | Bangkok | Krung Thep Maha Nakhon | Thailand | 10330 |
| 95 | Faculty of Medicine Siriraj Hospital ( Site 2400) | Bangkok | Krung Thep Maha Nakhon | Thailand | 10700 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 7684A-002
- MK-7684A-002
- KEYVIBE-002
- 2020-004034-38