Advanced/Metastatic Gastroesophageal Adenocarcinoma Clinical Trial
— LEAP-015Official title:
Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) Plus Chemotherapy Compared With Standard of Care Therapy as First-line Intervention in Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma (LEAP-015)
| Verified date | January 2024 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this study is to assess the efficacy and safety of lenvatinib (E7080/MK-7902) plus pembrolizumab (MK-3475) plus chemotherapy compared with chemotherapy alone in participants with advanced/metastatic gastroesophageal cancer. The primary study hypotheses are that lenvatinib plus pembrolizumab plus chemotherapy is superior to chemotherapy alone for both overall survival (OS) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR), in participants with programmed cell death-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 and in all participants.
| Status | Active, not recruiting |
| Enrollment | 890 |
| Est. completion date | February 2, 2026 |
| Est. primary completion date | February 2, 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Has histologically and/or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic gastroesophageal adenocarcinoma - Is not expected to require tumor resection during the treatment course - Has gastroesophageal adenocarcinoma that is not HER-2/neu positive - Has measurable disease as defined by RECIST 1.1 by scan with IV contrast as determined by the local site investigator - Male participants agree to refrain from donating sperm and agree to either remain abstinent from heterosexual intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for =7 days after last dose of lenvatinib or 90 days after last dose of chemotherapy-whichever comes last - Female participants not pregnant or breastfeeding are eligible to participate if not a women of childbearing potential (WOCBP), or if a WOCBP they either use a contraceptive method that is highly effective OR remain abstinent from heterosexual intercourse as their preferred and usual lifestyle, and do not donate eggs (ova, oocytes) to others or freeze/store for their own use, and abstain from breastfeeding during the intervention period through 120 days after last dose of pembrolizumab, 30 days after last dose of lenvatinib, or 180 days after last dose of chemotherapy-whichever occurs last - Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of study treatment - Has adequately controlled blood pressure with or without antihypertensive medications - Has adequate organ function Exclusion Criteria: - Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ) esophageal adenocarcinoma - Has had major surgery within 28 days prior to first dose of study interventions - Has had radiotherapy within 14 days of randomization - Has a known additional malignancy that is progressing or has required active treatment within the past 5 years - Has known CNS metastases and/or carcinomatous meningitis - Has severe hypersensitivity (=Grade 3) to treatment with an monoclonal antibody (mAb) or known sensitivity or intolerance to any component of lenvatinib, pembrolizumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum containing products - Has had an allogeneic tissue/solid organ transplant - Has perforation risks or significant gastrointestinal (GI) bleeding - Has GI obstruction, poor oral intake (CAPOX participants), or difficulty in taking oral medication (CAPOX participants) - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor - Has received prior therapy with anti- vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor or anti-VEGF mAb - Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug - Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) - Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation - Has inadequate cardiac function - Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease - Has poorly controlled diarrhea - Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. - Has peripheral neuropathy =Grade 2 - Has a known history of human immunodeficiency virus (HIV) or HIV 1/2 antibodies - Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection - Has weight loss of >20% within the last 3 months |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | CEMIC ( Site 0209) | Buenos Aires | |
| Argentina | Fundacion Favaloro ( Site 0201) | Buenos Aires | |
| Argentina | Hospital Aleman ( Site 0210) | Buenos Aires | |
| Argentina | Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0207) | Buenos Aires | |
| Argentina | IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 0202) | Caba | Buenos Aires |
| Argentina | Instituto Medico Alexander Fleming ( Site 0208) | Ciudad Autonoma de Buenos Aires | Buenos Aires |
| Argentina | Hospital Privado de Cordoba ( Site 0204) | Cordoba | |
| Australia | Royal Brisbane and Women s Hospital ( Site 2304) | Herston | Queensland |
| Australia | Nepean Hospital ( Site 2305) | Kingswood | New South Wales |
| Australia | Hollywood Private Hospital-Medical Oncology ( Site 2308) | Nedlands | Western Australia |
| Australia | Wollongong Hospital ( Site 2307) | Wollongong | New South Wales |
| Belgium | UZ Gent ( Site 1002) | Gent | Oost-Vlaanderen |
| Belgium | UZ Leuven ( Site 1004) | Leuven | Vlaams-Brabant |
| Belgium | AZ Delta ( Site 1006) | Roeselare | West-Vlaanderen |
| Belgium | CHU UCL Namur Site de Godinne ( Site 1005) | Yvoir | Namur |
| Canada | Queen Elizabeth II Health Sciences Centre ( Site 0101) | Halifax | Nova Scotia |
| Canada | Hamilton Health Sciences - Juravinski Site ( Site 0106) | Hamilton | Ontario |
| Canada | CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0103) | Sherbrooke | Quebec |
| Chile | IC La Serena Research ( Site 0410) | La Serena | Coquimbo |
| Chile | Bradfordhill ( Site 0404) | Santiago | Region M. De Santiago |
| Chile | Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0407) | Santiago | Region M. De Santiago |
| Chile | Fundacion Arturo Lopez Perez FALP ( Site 0403) | Santiago | Region M. De Santiago |
| Chile | Clinica Universidad Catolica del Maule ( Site 0411) | Talca | Maule |
| Chile | Centro Investigación del Cáncer James Lind ( Site 0414) | Temuco | Araucania |
| China | Beijing Cancer Hospital ( Site 2453) | Beijing | Beijing |
| China | Cancer Hospital Chinese Academy of Medical Sciences ( Site 2403) | Beijing | Beijing |
| China | Jilin Cancer Hospital ( Site 2438) | Changchun | Jilin |
| China | Hunan Cancer Hospital ( Site 2440) | Changsha | Hunan |
| China | Changzhou Cancer Hospital-Department of Oncology ( Site 2458) | Changzhou | Jiangsu |
| China | Fujian Provincial Cancer Hospital ( Site 2408) | Fuzhou | Fujian |
| China | The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Si | Fuzhou | Fujian |
| China | Nanfang Hospital ( Site 2456) | Guangzhou | Guangdong |
| China | The Affiliated Hospital Of Hainan Medical University-Cancer rehabilitation and palliative treatment | Haikou | Hainan |
| China | Sir Run Run Shaw Hospital ( Site 2412) | Hangzhou | Zhejiang |
| China | The First Affiliated Hospital of Zhejiang University ( Site 2414) | Hangzhou | Zhejiang |
| China | Harbin Medical University Cancer Hospital ( Site 2410) | Harbin | Heilongjiang |
| China | Anhui Provincial Hospital ( Site 2415) | Hefei | Anhui |
| China | First Hospital of Lanzhou University ( Site 2417) | Lanzhou | Gansu |
| China | LinYi Cancer Hospital-Gastrology department ( Site 2463) | Linyi | Shandong |
| China | Nanjing Drum Tower Hospital ( Site 2419) | Nanjing | Jiangsu |
| China | Nantong Tumor Hospital-Digestive Oncology ( Site 2464) | Nantong | Jiangsu |
| China | Shanghai East Hospital ( Site 2455) | Shanghai | Shanghai |
| China | Shanghai General Hospital ( Site 2424) | Shanghai | Shanghai |
| China | Fourth Hospital Of Hebei Medical University ( Site 2441) | Shijiazhuang | Hebei |
| China | Tianjin Medical University Cancer Institute & Hospital ( Site 2447) | Tianjin | Tianjin |
| China | Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2428) | Urumqi | Xinjiang |
| China | Hubei Cancer Hospital ( Site 2429) | Wuhan | Hubei |
| China | Tang Du Hospital ( Site 2432) | XI An | Shaanxi |
| China | The First Affiliated Hospital of Xiamen University ( Site 2420) | Xiamen | Fujian |
| China | The First Affiliated Hospital of Xiamen University ( Site 2446) | Xiamen | Fujian |
| China | Zhongshan Hospital Affiliated to Xiamen University ( Site 2421) | Xiamen | Fujian |
| China | Henan Cancer Hospital ( Site 2443) | Zhengzhou | Henan |
| Colombia | Clinica de la Costa S.A.S. ( Site 0502) | Barranquilla | Atlantico |
| Colombia | Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0501) | Bogota | Distrito Capital De Bogota |
| Colombia | Oncomedica S.A. ( Site 0507) | Monteria | Cordoba |
| Colombia | Instituto Cancerologico de Narino Ltda ( Site 0504) | Pasto | Narino |
| Colombia | Oncologos del Occidente S.A. ( Site 0525) | Pereira | Risaralda |
| Colombia | Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0508) | Valledupar | Cesar |
| Costa Rica | CIMCA-Hemato-Oncology ( Site 0601) | San José | San Jose |
| Costa Rica | Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 0602) | Santa Ana | San Jose |
| France | Institut du Cancer Avignon-Provence ( Site 1103) | Avignon | Vaucluse |
| France | Centre Francois Baclesse ( Site 1107) | Caen | Calvados |
| France | Hopital Henri Mondor ( Site 1105) | Creteil | Val-de-Marne |
| France | Centre Georges Francois Leclerc ( Site 1106) | Dijon | Cote-d Or |
| France | Centre Hospitalier Annecy Genevois ( Site 1117) | Epagny Metz-Tessy | Haute-Savoie |
| France | Hôpital Edouard Herriot ( Site 1116) | Lyon | Rhone-Alpes |
| France | CHU Hotel Dieu Nantes ( Site 1101) | Nantes | Pays-de-la-Loire |
| France | CHU Hopital Saint Antoine ( Site 1102) | Paris | |
| France | Hopital Saint Louis ( Site 1100) | Paris | |
| France | CHU Bordeaux Haut-Leveque ( Site 1110) | Pessac | Gironde |
| Germany | Charite Berlin Campus Virchow-Klinikum ( Site 1202) | Berlin | |
| Germany | Krankenhaus Nordwest ( Site 1205) | Frankfurt am Main | Hessen |
| Germany | Facharztzentrum Eppendorf ( Site 1201) | Hamburg | |
| Germany | Medizinische Hochschule Hannover ( Site 1210) | Hannover | Niedersachsen |
| Germany | Universitaetsklinikum Leipzig ( Site 1211) | Leipzig | Sachsen |
| Germany | Klinikum Rechts der Isar der TU Muenchen ( Site 1200) | Muechen | Bayern |
| Germany | Universitaetsklinikum Regensburg ( Site 1203) | Regensburg | Bayern |
| Guatemala | Clinica Privada Dr Rixci Ramirez Fallas ( Site 0702) | Guatemala | |
| Guatemala | Medi-K Cayala ( Site 0700) | Guatemala | |
| Guatemala | Oncologika S.A. ( Site 0704) | Guatemala | |
| Guatemala | Oncomedica ( Site 0701) | Guatemala | |
| Guatemala | Sanatorio Nuestra Senora del Pilar ( Site 0705) | Guatemala | |
| Guatemala | Soluciones Gastrointestinales S.A. ( Site 0706) | Guatemala | |
| Hong Kong | Prince of Wales Hospital ( Site 2503) | Hong Kong | |
| Hong Kong | Princess Margaret Hospital. ( Site 2502) | Hong Kong | |
| Hong Kong | Queen Mary Hospital ( Site 2501) | Hong Kong | |
| Ireland | Beaumont Hospital ( Site 1402) | Dublin | |
| Ireland | St James Hospital ( Site 1400) | Dublin | Leinster |
| Israel | Soroka Medical Center ( Site 1507) | Be'er Sheva | |
| Israel | Hillel Yaffe Medical Center ( Site 1503) | Hadera | |
| Israel | Rambam Health Care Campus-Oncology Division ( Site 1502) | Haifa | |
| Israel | Hadassah Ein Kerem Medical Center ( Site 1501) | Jerusalem | |
| Israel | Meir Medical Center ( Site 1504) | Kfar-Saba | |
| Israel | Rabin Medical Center ( Site 1506) | Petah Tikva | |
| Israel | Sourasky Medical Center ( Site 1500) | Tel Aviv | |
| Italy | Azienda Ospedaliera Mater Domini-Translational Oncology Unit ( Site 1611) | Catanzaro | |
| Italy | Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 1608) | Meldola | Abruzzo |
| Italy | Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1610) | Milan | Lombardia |
| Italy | IRCCS Ospedale San Raffaele di Milano ( Site 1603) | Milano | |
| Italy | A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1604) | Napoli | |
| Italy | Humanitas Research Hospital ( Site 1600) | Rozzano | Lombardia |
| Italy | Presidio Ospedaliero Universitario Santa Maria della Misericordia ( Site 1609) | Udine | Friuli-Venezia Giulia |
| Italy | AULSS8 Berica-Ospedale S.Bortolo ( Site 1607) | Vicenza | Veneto |
| Japan | Hyogo Cancer Center ( Site 2621) | Akashi | Hyogo |
| Japan | National Hospital Organization Kyushu Cancer Center ( Site 2609) | Fukuoka | |
| Japan | Kansai Medical University Hospital ( Site 2622) | Hirakata | Osaka |
| Japan | Hiroshima City Hiroshima Citizens Hospital ( Site 2612) | Hiroshima | |
| Japan | Ibaraki Prefectural Central Hospital ( Site 2618) | Kasama | Ibaraki |
| Japan | National Cancer Center Hospital East ( Site 2601) | Kashiwa | Chiba |
| Japan | Kagawa University Hospital ( Site 2611) | Kita-gun | Kagawa |
| Japan | Saitama Cancer Center ( Site 2604) | Kitaadachi-gun | Saitama |
| Japan | Kobe City Medical Center General Hospital ( Site 2606) | Kobe | Hyogo |
| Japan | National Hospital Organization Shikoku Cancer Center ( Site 2610) | Matsuyama | Ehime |
| Japan | Aichi Cancer Center Hospital ( Site 2603) | Nagoya | Aichi |
| Japan | Osaka International Cancer Institute ( Site 2607) | Osaka | |
| Japan | Kindai University Hospital ( Site 2600) | Osakasayama | Osaka |
| Japan | National Cancer Center Hospital ( Site 2602) | Tokyo | |
| Japan | The Cancer Institute Hospital of JFCR ( Site 2605) | Tokyo | |
| Japan | Kanagawa Cancer Center ( Site 2608) | Yokohama | Kanagawa |
| Korea, Republic of | Hallym University Sacred Heart Hospital ( Site 2806) | Anyang-si | Kyonggi-do |
| Korea, Republic of | Konyang University ( Site 2807) | Daejeon | Taejon-Kwangyokshi |
| Korea, Republic of | Seoul National University Bundang Hospital ( Site 2804) | Seongnam-si | Kyonggi-do |
| Korea, Republic of | Gangnam Severance Hospital ( Site 2805) | Seoul | |
| Korea, Republic of | Korea University Guro Hospital ( Site 2808) | Seoul | |
| Korea, Republic of | Samsung Medical Center ( Site 2801) | Seoul | |
| Korea, Republic of | Seoul National University Hospital ( Site 2803) | Seoul | |
| Korea, Republic of | Severance Hospital Yonsei University Health System ( Site 2800) | Seoul | |
| Korea, Republic of | Asan Medical Center ( Site 2802) | Songpagu | Seoul |
| Poland | Przychodnia Lekarska KOMED ( Site 1701) | Konin | Wielkopolskie |
| Poland | Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 1703) | Poznan | Wielkopolskie |
| Poland | Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1702) | Przemysl | Podkarpackie |
| Poland | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 1704) | Warszawa | Mazowieckie |
| Poland | Dolnoslaskie Centrum Onkologii. ( Site 1712) | Wroclaw | Dolnoslaskie |
| Russian Federation | Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1816) | Chelyabinsk | Chelyabinskaya Oblast |
| Russian Federation | Blokhin National Medical Oncology ( Site 1800) | Moscow | Moskva |
| Russian Federation | Central Clinical Hospital with Polyclinic ( Site 1801) | Moscow | Moskva |
| Russian Federation | National Medical and Surgical Center n.a.N.I.Pirogov ( Site 1805) | Moscow | Moskva |
| Russian Federation | St Petersburg City Clinical Oncology Dispensary ( Site 1808) | Saint Petersburg | Sankt-Peterburg |
| Russian Federation | Leningrad Regional Oncology Center ( Site 1810) | Saint-Petersburg | Sankt-Peterburg |
| Russian Federation | Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1809) | Saint-Petersburg | Sankt-Peterburg |
| Russian Federation | Medical University REAVIZ ( Site 1814) | Samara | Samarskaya Oblast |
| Russian Federation | Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1821) | Yaroslavl | Yaroslavskaya Oblast |
| Spain | Hospital General Universitari Vall d Hebron ( Site 1907) | Barcelona | |
| Spain | Hospital General Gregorio Maranon de Madrid ( Site 1904) | Madrid | |
| Spain | Hospital Universitario General de Asturias ( Site 1901) | Oviedo | Asturias |
| Spain | Hospital Universitario Marques de Valdecilla ( Site 1902) | Santander | Cantabria |
| Taiwan | China Medical University Hospital ( Site 2903) | Taichung | |
| Taiwan | National Cheng Kung University Hospital ( Site 2904) | Tainan | |
| Taiwan | National Taiwan University Hospital ( Site 2901) | Taipei | |
| Taiwan | Chang Gung Medical Foundation. Linkou ( Site 2902) | Taoyuan | |
| Turkey | Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2003) | Ankara | |
| Turkey | Memorial Ankara Hastanesi ( Site 2004) | Ankara | |
| Turkey | Trakya Universitesi Tip Fakultesi ( Site 2000) | Edirne | |
| Turkey | Ataturk Universitesi Tip Fakultesi Hastanesi ( Site 2005) | Erzurum | |
| Turkey | Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 2002) | Istanbul | |
| Turkey | Ege Universitesi Tip Fakultesi Hastanesi ( Site 2001) | Izmir | |
| Turkey | Sakarya Universitesi Tip Fakultesi ( Site 2007) | Sakarya | Istanbul |
| United Kingdom | Addenbrooke's Hospital ( Site 2200) | Cambridge | Cambridgeshire |
| United Kingdom | University Hospital Coventry and Warwickshire NHS Trust ( Site 2205) | Coventry | Warwickshire |
| United Kingdom | Ninewells Hospital and Medical School ( Site 2207) | Dundee | Dundee City |
| United Kingdom | The Beatson West of Scotland Cancer Centre ( Site 2204) | Glasgow | Glasgow City |
| United Kingdom | Royal Marsden NHS Foundation Trust ( Site 2202) | London | London, City Of |
| United Kingdom | University College London Hospitals NHS Foundation Trust ( Site 2201) | London | London, City Of |
| United Kingdom | The Christie NHS Foundation Trust ( Site 2209) | Manchester | |
| United Kingdom | Royal Marsden NHS Trust ( Site 2203) | Sutton | Surrey |
| United States | Johns Hopkins University ( Site 0052) | Baltimore | Maryland |
| United States | Dana Farber Cancer Center ( Site 0019) | Boston | Massachusetts |
| United States | Henry Ford Health System ( Site 0023) | Detroit | Michigan |
| United States | Cancer and Hematology Centers of Western Michigan ( Site 0025) | Grand Rapids | Michigan |
| United States | UCLA Hematology/Oncology - Santa Monica ( Site 0003) | Los Angeles | California |
| United States | James Graham Brown Cancer Center ( Site 0017) | Louisville | Kentucky |
| United States | Memorial Sloan Kettering Cancer Center ( Site 0032) | New York | New York |
| United States | Mount Sinai Hospital ( Site 0051) | New York | New York |
| United States | AHN West Penn Hospital-AHN Esophageal and Lung Institute ( Site 0058) | Pittsburgh | Pennsylvania |
| United States | Washington University School of Medicine ( Site 0027) | Saint Louis | Missouri |
| United States | Georgetown University Medical Center ( Site 0009) | Washington | District of Columbia |
| United States | UMASS Memorial Medical Center ( Site 0020) | Worcester | Massachusetts |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC | Eisai Inc. |
United States, Argentina, Australia, Belgium, Canada, Chile, China, Colombia, Costa Rica, France, Germany, Guatemala, Hong Kong, Ireland, Israel, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) | Hematologic DLTs were defined as Grade 4 neutropenia lasting for =7 days, Grade 3 or Grade 4 febrile neutropenia, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, or Grade 4 anemia. Other nonhematologic toxicities considered a DLT included any other Grade 4 or Grade 5 toxicity, Grade 3 toxicities lasting >3 days (excluding nausea, vomiting, and diarrhea controlled by medical intervention within 72 hours, and Grade 3 rash in the absence of desquamation with no mucosal involvement), Grade 3 hypertension not able to be controlled by medication, =Grade 3 gastrointestinal perforation, =Grade 3 wound dehiscence requiring medical or surgical intervention, or any grade thromboembolic event. The number of participants in Part 1 with DLTs will be reported by treatment arm. | Up to ~21 days | |
| Primary | Part 1: Number of Participants with Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 1 with AEs will be reported by treatment arm. | Up to ~28 months | |
| Primary | Part 1: Number of Participants who Discontinued Study Treatment Due to an AE | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 1 that discontinued study due to an AE will be reported by treatment arm. | Up to ~25 months | |
| Primary | Part 2: Overall Survival (OS) in Participants with Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) =1 | OS is defined as the time from randomization to death due to any cause. OS will be reported by treatment arm for PD-L1 CPS =1 participants in Part 2. | Up to ~41 months | |
| Primary | Part 2: OS in All Participants | OS is defined as the time from randomization to death due to any cause. OS will be reported by treatment arm for all participants in Part 2. | Up to ~41 months | |
| Primary | Part 2: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants with PD-L1 CPS =1 | PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 by BICR or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, 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 demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. PFS will be reported by treatment arm for PD-L1 CPS =1 participants in Part 2. | Up to ~31 months | |
| Primary | Part 2: PFS Per RECIST 1.1 as Assessed by BICR in All Participants | PFS is defined as the time from randomization to the first documented PD per RECIST 1.1 by BICR or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, 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 demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. PFS will be reported by treatment arm for all participants in Part 2. | Up to ~31 months | |
| Secondary | Part 2: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS =1 | ORR is defined as the percentage of participants in the analysis population 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) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and assessed by BICR. ORR will be reported by treatment arm for PD-L1 CPS =1 participants in Part 2. | Up to ~31 months | |
| Secondary | Part 2: ORR Per RECIST 1.1 as Assessed by BICR in All Participants | ORR is defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and assessed by BICR. ORR will be reported by treatment arm for all participants in Part 2. | Up to ~31 months | |
| Secondary | Part 2: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS =1 | For participants who demonstrated confirmed CR or PR, DOR is defined as the time from the first CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) to subsequent PD or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, 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 demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR will be reported by treatment arm for PD-L1 CPS =1 participants in Part 2. | Up to ~31 months | |
| Secondary | Part 2: DOR Per RECIST 1.1 as Assessed by BICR in All Participants | For participants who demonstrated confirmed CR or PR, DOR is defined as the time from the first CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) to subsequent PD or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, 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 demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR will be reported by treatment arm for all participants in Part 2. | Up to ~31 months | |
| Secondary | Part 2: Number of Participants with AEs | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 2 with AEs will be reported by treatment arm. | Up to ~28 months | |
| Secondary | Part 2: Number of Participants who Discontinued Study Treatment Due to an AE | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 2 that discontinued study due to an AE will be reported by treatment arm. | Up to ~25 months |