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)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05224141
Collaborator
(none)
450
71
2
62.5
6.3
0.1

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
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
450 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-Blind Study of MK-7684A in Combination With Etoposide and Platinum Followed by MK-7684A vs Atezolizumab in Combination With Etoposide and Platinum Followed by Atezolizumab for the First-Line Treatment of Participants With Extensive-Stage Small Cell Lung Cancer
Actual Study Start Date :
Mar 24, 2022
Anticipated Primary Completion Date :
May 8, 2025
Anticipated Study Completion Date :
Jun 7, 2027

Arms and Interventions

Arm Intervention/Treatment
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:
  • MK-7684A
  • 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:
  • PLATINOL-AQ®
  • 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:
  • PARAPLATIN®
  • 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:
  • PLATINOL-AQ®
  • Biological: Atezolizumab
    Atezolizumab 1200 mg administered via IV infusion Q3W on Day 1 of each cycle until discontinuation criteria are met.
    Other Names:
  • TECENTRIQ®
  • 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:
  • PARAPLATIN®
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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).

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    12. 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.

    13. 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.

    14. 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.

    15. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Has histologically or cytologically confirmed diagnosis of ES-SCLC in need of first-line therapy

    • 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

    • Males agree to use contraception, refrain from donating sperm, and abstain from heterosexual intercourse

    • 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

    • Has measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

    • Has a predicted life expectancy of >3 months

    Exclusion Criteria:
    • Is considered a poor medical risk due to a serious, uncontrolled medical disorder or non-malignant systemic disease

    • Has received prior treatment for Small Cell Lung Cancer (SCLC)

    • Is expected to require any other form of antineoplastic therapy for SCLC while on study

    • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

    • Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration

    • 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

    • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years

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

    • Has a history of severe hypersensitivity reaction (≥Grade 3) to any study intervention and/or any of its excipients

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

    • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease

    • Has a known history of, or active, neurologic paraneoplastic syndrome

    • Has an active infection requiring systemic therapy

    • Has a known history of human immunodeficiency virus (HIV) infection

    • Has a known history of Hepatitis B or known active Hepatitis C virus infection

    • Has had an allogenic tissue/solid organ transplant

    • 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

    • Has symptomatic ascites or pleural effusion

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    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.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT05224141
    Other Study ID Numbers:
    • 7684A-008
    • MK-7684A-008
    • KEYVIBE-008
    • jRCT2021220008
    • 2021-005034-42
    First Posted:
    Feb 4, 2022
    Last Update Posted:
    Aug 23, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 23, 2022