Pembrolizumab/Vibostolimab (MK-7684A) or Atezolizumab in Combination With Chemotherapy in First Line Treatment of Extensive-Stage Small Cell Lung Cancer (MK-7684A-008, KEYVIBE-008)
Study Details
Study Description
Brief Summary
This study will evaluate the combination of a fixed dose pembrolizumab/vibostolimab co-formulation (MK-7684A) with etoposide/platinum chemotherapy followed by MK-7684A compared to the combination of atezolizumab with etoposide/platinum chemotherapy followed by atezolizumab in the first-line treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC). The primary hypothesis is, with respect to overall survival, MK-7684A in combination with the background therapy of etoposide/platinum followed by MK-7684A, is superior to atezolizumab in combination with the background therapy of etoposide/platinum followed by atezolizumab.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Pembrolizumab/Vibostolimab Participants will receive 4 cycles (each cycle is 3 weeks) of a fixed-dose coformulation of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684A) every 3 weeks (Q3W), in combination with 100 mg/m^2 etoposide, and platinum (Area Under the Curve (AUC) 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of MK-7684A Q3W until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1. |
Biological: Pembrolizumab/Vibostolimab Co-Formulation
Pembrolizumab 200 mg plus vibostolimab 200 mg fixed dose coformulation administered via IV infusion Q3W on Day 1 of each cycle until discontinuation criteria are met.
Other Names:
Drug: Saline placebo
Saline solution administered via IV infusion on Cycle 1 (and Q3W as needed beyond Cycle 1)
Drug: Etoposide
Etoposide 100 mg/m^2 administered via IV infusion Q3W on Days 1 2, 3 of each cycle for up to 4 cycles
Drug: Cisplatin
Cisplatin 75 mg/m^2 administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.
Other Names:
Drug: Carboplatin
Carboplatin AUC 5 mg/mL/min administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.
Other Names:
|
Active Comparator: Atezolizumab Participants will receive 4 cycles (each cycle is 3 weeks) of 1200 mg atezolizumab Q3W, in combination with 100 mg/m^2 etoposide and platinum (AUC 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of atezolizumab Q3W until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1. |
Drug: Saline placebo
Saline solution administered via IV infusion on Cycle 1 (and Q3W as needed beyond Cycle 1)
Drug: Etoposide
Etoposide 100 mg/m^2 administered via IV infusion Q3W on Days 1 2, 3 of each cycle for up to 4 cycles
Drug: Cisplatin
Cisplatin 75 mg/m^2 administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.
Other Names:
Biological: Atezolizumab
Atezolizumab 1200 mg administered via IV infusion Q3W on Day 1 of each cycle until discontinuation criteria are met.
Other Names:
Drug: Carboplatin
Carboplatin AUC 5 mg/mL/min administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [Up to approximately 37 months]
Overall Survival (OS) is the time from randomization to the date of death due to any cause.
Secondary Outcome Measures
- Progression-Free Survival (PFS) [Up to approximately 26 months]
Progression-Free Survival (PFS) is the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first.
- Objective Response Rate (ORR) [Up to approximately 37 months]
Objective Response Rate (ORR) is 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).
- Duration of Response (DOR) [Up to approximately 37 months]
Duration of Response (DOR) is the time from first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), until progressive disease (PD) or death.
- Percentage of Participants Who Experienced an Adverse Event (AE) [Up to approximately 60 months]
An AE is 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.
- Percentage of Participants Who Discontinued Study Treatment Due to an AE [Up to approximately 60 months]
An AE is 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.
- Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [Baseline and up to approximately 37 months]
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of individuals with cancer. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall QoL during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome.
- Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 [Baseline and up to approximately 37 months]
The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function.
- Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30 [Baseline and up to approximately 37 months]
The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea.
- Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) [Baseline and up to approximately 37 months]
The EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing.
- Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 [Baseline and up to approximately 37 months]
EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain.
- Time to True Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30 [Baseline and up to approximately 37 months]
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of individuals with cancer. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall QoL during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
- TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 [Baseline and up to approximately 37 months]
The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
- TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30 [Baseline and up to approximately 37 months]
The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
- TTD in Cough Score (Item 31) on the EORTC QLQ-LC13 [Baseline and up to approximately 37 months]
The EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
- TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 [Baseline and up to approximately 37 months]
The EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Has histologically or cytologically confirmed diagnosis of ES-SCLC in need of first-line therapy
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Has ES-SCLC defined as Stage IV (T any, N any, M1a/b/c) by the American Joint Committee on Cancer, Eighth Edition or T3-T4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan
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Males agree to use contraception, refrain from donating sperm, and abstain from heterosexual intercourse
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Females are not pregnant or breastfeeding, is not a woman of childbearing potential (WOCBP) or is a WOCBP who uses a highly effective contraceptive method, or is abstinent from heterosexual intercourse
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Has measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
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Has a predicted life expectancy of >3 months
Exclusion Criteria:
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Is considered a poor medical risk due to a serious, uncontrolled medical disorder or non-malignant systemic disease
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Has received prior treatment for Small Cell Lung Cancer (SCLC)
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Is expected to require any other form of antineoplastic therapy for SCLC while on study
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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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Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
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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 prior the first dose of study medication
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Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
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Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
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Has a history of severe hypersensitivity reaction (≥Grade 3) to any study intervention and/or any of its excipients
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Has an active autoimmune disease that has required systemic treatment in past 2 years
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Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
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Has a known history of, or active, neurologic paraneoplastic syndrome
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Has an active infection requiring systemic therapy
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Has a known history of human immunodeficiency virus (HIV) infection
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Has a known history of Hepatitis B or known active Hepatitis C virus infection
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Has had an allogenic tissue/solid organ transplant
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Has had major surgery within prior 3 weeks or has not recovered adequately from toxicity and/or complications from an intervention prior to receiving the first dose of study intervention
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Has symptomatic ascites or pleural effusion
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Los Angeles Hematology Oncology Medical Group ( Site 0006) | Los Angeles | California | United States | 90017 |
2 | Boca Raton Regional Hospital-Lynn Cancer Institute ( Site 0014) | Boca Raton | Florida | United States | 33486 |
3 | Fort Wayne Medical Oncology and Hematology ( Site 0013) | Fort Wayne | Indiana | United States | 46804 |
4 | Cancer and Hematology Centers of Western Michigan ( Site 0001) | Grand Rapids | Michigan | United States | 49503 |
5 | Hattiesburg Clinic Hematology/Oncology ( Site 0003) | Hattiesburg | Mississippi | United States | 39401 |
6 | Lancaster General Hospital - Ann B Barshinger Cancer Institute ( Site 0005) | Lancaster | Pennsylvania | United States | 17601 |
7 | Blue Ridge Cancer Care ( Site 0015) | Blacksburg | Virginia | United States | 24060 |
8 | Instituto de Investigaciones Clínicas Mar del Plata ( Site 0201) | Mar del Plata | Buenos Aires | Argentina | 7600 |
9 | Hospital Provincial del Centenario ( Site 0205) | Rosario | Santa Fe | Argentina | 2002 |
10 | Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Medical Oncology ( Site 0200) | Buenos Aires | Argentina | 1431 | |
11 | Calvary Mater Newcastle ( Site 2703) | Waratah | New South Wales | Australia | 2298 |
12 | Frankston Hospital-Oncology and Haematology ( Site 2702) | Frankston | Victoria | Australia | 3199 |
13 | Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 2701) | St Albans | Victoria | Australia | 3021 |
14 | Ordensklinikum Linz GmbH Elisabethinen-Department of Pneumology ( Site 0505) | Linz | Oberosterreich | Austria | 4020 |
15 | Kepler Universitätsklinikum ( Site 0507) | Linz | Oberosterreich | Austria | 4021 |
16 | Medizinische Universität Graz ( Site 0504) | Graz | Steiermark | Austria | 8036 |
17 | Beijing Peking Union Medical College Hospital ( Site 2921) | Beijing | Beijing | China | 100730 |
18 | Fujian Provincial Cancer Hospital-oncology department ( Site 2904) | Fuzhou | Fujian | China | 350014 |
19 | Shanghai Chest Hospital-Oncology department ( Site 2900) | Shanghai | Shanghai | China | 200030 |
20 | Sir Run Run Shaw Hospital-Medical Oncology ( Site 2906) | Hangzhou | Zhejiang | China | 310016 |
21 | Vaasan Keskussairaala-Department of Clinical Oncology ( Site 0700) | Vaasa | Pohjanmaa | Finland | 65130 |
22 | Oulun yliopistollinen sairaala-Oncology and Hematology ( Site 0702) | Oulu | Pohjois-Pohjanmaa | Finland | 90220 |
23 | Turku University Hospital-The Department of Pulmonary Medicine ( Site 0701) | Turku | Varsinais-Suomi | Finland | 20520 |
24 | Assistance Publique Hôpitaux de Marseille - Hôpital Nord ( Site 0805) | Marseille | Bouches-du-Rhone | France | 13915 |
25 | CHU de Toulouse - Hopital Larrey-service de pneumologie ( Site 0800) | Toulouse | Haute-Garonne | France | 31059 |
26 | Lungenfachklinik Immenhausen-Thoracic Oncology ( Site 0907) | Immenhausen | Hessen | Germany | 34376 |
27 | LungenClinic Grosshansdorf-Onkologie ( Site 0903) | Grosshansdorf | Schleswig-Holstein | Germany | 22927 |
28 | SRH Wald-Klinikum Gera-Lungenkrebszentrum ( Site 0900) | Gera | Thuringen | Germany | 07548 |
29 | Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 1105) | Kecskemét | Bacs-Kiskun | Hungary | 6000 |
30 | Petz Aladar Egyetemi Oktato Korhaz-Pulmonológia (Dr. Szalai Zsuzsanna) ( Site 1102) | Gyor | Gyor-Moson-Sopron | Hungary | 9024 |
31 | Torokbalint Tudogyogyintezet-Onkopulmonologiai Jarobeteg Centrum ( Site 1101) | Törökbálint | Pest | Hungary | 2045 |
32 | Somogy Megyei Kaposi Mór Oktató Kórház-Pulmonologiai Osztaly ( Site 1104) | Kaposvár | Somogy | Hungary | 7400 |
33 | Rambam Health Care Campus-Oncology ( Site 1301) | Haifa | Israel | 3109601 | |
34 | Shaare Zedek Medical Center-Oncology ( Site 1300) | Jerusalem | Israel | 9103102 | |
35 | Sheba Medical Center-ONCOLOGY ( Site 1302) | Ramat Gan | Israel | 5265601 | |
36 | Azienda Ospedaliera Dei Colli-U.O.C Pneumologia Oncologica DH PNL ONC ( Site 1402) | Naples | Campania | Italy | 80131 |
37 | Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 1401) | Milan | Lombardia | Italy | 20133 |
38 | Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1403) | Rozzano | Milano | Italy | 20089 |
39 | Istituto Nazionale Tumori Regina Elena-Oncologia Medica 2 ( Site 1400) | Rome | Roma | Italy | 00144 |
40 | Kurume University Hospital ( Site 3014) | Kurume | Fukuoka | Japan | 830-0011 |
41 | National Hospital Organization Hokkaido Cancer Center ( Site 3015) | Sapporo | Hokkaido | Japan | 003-0804 |
42 | Kanazawa University Hospital ( Site 3006) | Kanazawa | Ishikawa | Japan | 920-8641 |
43 | Sendai Kousei Hospital ( Site 3001) | Sendai | Miyagi | Japan | 9800873 |
44 | Kansai Medical University Hospital ( Site 3009) | Hirakata | Osaka | Japan | 573-1191 |
45 | Shizuoka Cancer Center ( Site 3007) | Nagaizumi | Shizuoka | Japan | 411-8777 |
46 | Japanese Foundation for Cancer Research ( Site 3003) | Koto | Tokyo | Japan | 135-8550 |
47 | National Hospital Organization Kyushu Medical Center ( Site 3013) | Fukuoka | Japan | 810-8563 | |
48 | Okayama University Hospital ( Site 3011) | Okayama | Japan | 700-8558 | |
49 | Chonnam National University Hwasun Hospital-Pulmonology ( Site 2800) | Hwasun | Jeonranamdo | Korea, Republic of | 58128 |
50 | Kyungpook National University Chilgok Hospital-Pulmonology ( Site 2801) | Deagu | Taegu-Kwangyokshi | Korea, Republic of | 41404 |
51 | Chungnam national university hospital-Department of Internal Medicine ( Site 2802) | Daejeon | Taejon-Kwangyokshi | Korea, Republic of | 35015 |
52 | Korea University Guro Hospital-Internal Medicine ( Site 2803) | Seoul | Korea, Republic of | ||
53 | Klaipeda University Hospital-Oncology chemotherapy ( Site 1502) | Klaipeda | Klaipedos Miestas | Lithuania | 92288 |
54 | National Cancer Institute-Department of Thoracic Surgery and Oncology ( Site 1501) | Vilnius | Vilniaus Miestas | Lithuania | LT-08660 |
55 | Hospital of Lithuanian University of Health Sciences Kauno klinikos-Pulmonology ( Site 1500) | Kaunas | Lithuania | LT-50161 | |
56 | Actualidad Basada en la Investigación del Cáncer-Lung Cancer ( Site 0403) | Guadalajara | Jalisco | Mexico | 44680 |
57 | Centro de Investigacion Clinica de Oaxaca ( Site 0410) | Oaxaca | Mexico | 68020 | |
58 | Medische Centrum Leeuwarden ( Site 1619) | Leeuwarden | Fryslan | Netherlands | 8934 AD |
59 | Ziekenhuis Rijnstate ( Site 1606) | Arnhem | Gelderland | Netherlands | 6921SC |
60 | Maastricht UMC+-Pulmonary disease ( Site 1602) | Maastricht | Limburg | Netherlands | 6229 HX |
61 | Jeroen Bosch Hospital-Pulmonology ( Site 1605) | Den Bosch | Noord-Brabant | Netherlands | 5223 GZ |
62 | Isala, locatie Zwolle-Poli Longziekten ( Site 1612) | Zwolle | Overijssel | Netherlands | 8025 AB |
63 | Erasmus Medisch Centrum ( Site 1621) | Rotterdam | Zuid-Holland | Netherlands | 3015 CE |
64 | Martini Ziekenhuis ( Site 1618) | Groningen | Netherlands | 9728 NT | |
65 | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier | Warszawa | Mazowieckie | Poland | 02-781 |
66 | Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1703) | Przemysl | Podkarpackie | Poland | 37-700 |
67 | Szpital Specjalistyczny w Prabutach Spolka z o.o. ( Site 1706) | Prabuty | Pomorskie | Poland | 82-550 |
68 | Hospital Universitario 12 de Octubre-Medical Oncology ( Site 2102) | Madrid | Madrid, Comunidad De | Spain | 28041 |
69 | H.R.U Málaga - Hospital General-Oncology ( Site 2104) | Málaga | Malaga | Spain | 29011 |
70 | Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 2100) | Barcelona | Spain | 08035 | |
71 | Hospital Universitario Virgen Macarena-Unidad de Investigación Oncológica ( Site 2103) | Sevilla | Spain | 41009 |
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-008
- MK-7684A-008
- KEYVIBE-008
- jRCT2021220008
- 2021-005034-42