Urothelial Carcinoma Clinical Trial
Official title:
A Phase 3, Randomized, Double-blind Study to Compare the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Lenvatinib (E7080/MK-7902) Versus Pembrolizumab and Placebo as First Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma in Cisplatin-ineligible Participants Whose Tumors Express PD-L1, and in Participants Ineligible for Any Platinum-containing Chemotherapy Regardless of PD-L1 Expression (LEAP-011)
| 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 evaluate the efficacy and safety of lenvatinib (MK-7902/E7080) in combination with pembrolizumab (MK-3475) in the treatment of cisplatin-ineligible participants with a Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10, or in participants ineligible for any platinum-containing chemotherapy regardless of CPS, with advanced/unresectable or metastatic urothelial carcinoma (UC). The primary hypotheses for this study are that: 1. Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo 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), and 2. Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Overall Survival (OS). With Amendment 3 (effective: September [Sep]-24-2021) participants discontinued lenvatinib and placebo; participants who remained on treatment in the study arms received open-label pembrolizumab. With Amendment 3 the external Data Monitoring Committee was discontinued. With Amendment 4 (effective: December-5-2022) Second Course will no longer be offered. Any participant receiving Second Course treatment prior to initiation of Amendment 4 will be able to complete treatment as planned. With Amendment 4 study participation will end after the final administration of pembrolizumab. Participants who either complete 35 administrations of pembrolizumab or discontinue pembrolizumab will discontinue from the study following the safety follow-up visit. AEs and spontaneously reported pregnancies will be reported and followed per protocol. All participants in efficacy follow-up prior to initiation of Amendment 4 will stop efficacy assessments and be discontinued from the study. All participants in survival follow-up prior to initiation of Amendment 4 are considered to have completed the study and should have a final survival contact. The overall study ends when the last participant completes the last study-related contact or visit, withdraws from the study, or is lost to follow-up.
| Status | Active, not recruiting |
| Enrollment | 487 |
| Est. completion date | July 1, 2024 |
| Est. primary completion date | July 26, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Has a histologically or cytologically confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial carcinoma (UC) of the renal pelvis, ureter (upper urinary tract), bladder, or urethra. - Has =1 measurable target lesion per RECIST 1.1 as assessed by the local site investigator/radiologist. - Has provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated and adequate for Programmed Death-Ligand 1 (PD-L1) evaluation. - Has received no prior systemic chemotherapy for advanced or metastatic UC with the following exceptions: - Neoadjuvant (prior to surgery) platinum-based chemotherapy for treatment of muscle-invasive bladder cancer with recurrence >12 months from completion of the therapy is permitted. - Adjuvant (following surgery) platinum-based chemotherapy following radical cystectomy, with recurrence >12 months from completion of the therapy, is permitted. - Meets criteria for either option a or option b (below): - a. Has a tumor(s) with PD-L1 combined positive score (CPS) =10 and is considered ineligible to receive cisplatin-based combination therapy, based on 1 of the following: - Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 2 within 7 days prior to randomization - National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade =2 audiometric hearing loss - NCI CTCAE Version 4.0 Grade =2 peripheral neuropathy OR - b. In the opinion of the investigator, is considered ineligible to receive any platinum-based chemotherapy (i.e., ineligible for cisplatin and carboplatin) based on: - ECOG PS of 2 within 7 days prior to randomization and =1 of the following: - Documented visceral metastatic disease - NCI CTCAE Version 4.0 Grade =2 audiometric hearing loss - NCI CTCAE Version 4.0 Grade =2 peripheral neuropathy - Other reason for the participant's being unable to receive both cisplatin and carboplatin safely. Additional criteria for platinum ineligibility will be considered and allowed on a case-by-case basis, following consultation with the Sponsor. Note: Participants considered ineligible for any platinum-based chemotherapy are eligible for this study regardless of their tumor PD-L1 status. - Has ECOG PS 0, 1, or 2 within 7 days prior to randomization and a life expectancy of =3 months. - Male participants are eligible to participate if they agree to the following during the treatment period and for =30 days after the last dose of pembrolizumab or lenvatinib/placebo: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR - Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below: - Agrees to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration. - A female participant is eligible to participate if she is not pregnant or breastfeeding and if she is not a WOCBP OR is a WOCBP and is using a contraceptive method that is highly effective (with a failure rate of <1% per year) with low user dependency, or is abstinent from heterosexual intercourse as her preferred and usual lifestyle during the intervention period and for =120 days post pembrolizumab or =30 days post lenvatinib/placebo. - Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 mm Hg at screening and no change in antihypertensive medications within 1 week prior to randomization. - Has adequate organ function. Exclusion Criteria: - Has disease that is suitable for local therapy administered with curative intent (e.g. chemotherapy and radiation for Stage 3 disease). - Has tumor with any neuroendocrine or small cell component. - Has a history of a gastrointestinal condition or procedure (e.g. gastric bypass, malabsorption) that, in the opinion of the investigator, may affect oral drug absorption. - Has had major surgery within 3 weeks prior to the first dose of study treatment - Has a pre-existing Grade =3 gastrointestinal or non-gastrointestinal fistula. - Has radiographic evidence of major blood vessel invasion/infiltration, or has had clinically significant hemoptysis (=0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks prior to the first dose of study treatment. - Has had significant cardiovascular impairment within 12 months of the first dose of study treatment, such as history of New York Heart Association (NYHA) >Class II congestive heart failure, unstable angina, myocardial infarction or cerebrovascular accident (CVA)/stroke, cardiac revascularization procedure, or cardiac arrhythmia associated with hemodynamic instability. - Has known intolerance or severe hypersensitivity (Grade =3) to pembrolizumab or lenvatinib or any of their excipients - Has received lenvatinib as monotherapy or in combination with a programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitor or has previously been enrolled in a clinical study evaluating lenvatinib for bladder cancer, regardless of the treatment received. - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 inhibitor, indoleamine-pyrrole 2,3 dioxygenase (IDO1) inhibitor, or agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], OX 40, CD137), or any other antibody or drug targeting T-cell costimulatory pathways in the adjuvant or advanced/metastatic setting. - Has received prior radiotherapy to a metastatic site without the use of chemotherapy radiosensitization within 3 weeks of the first dose of study treatment, with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks before the start of study treatment. Participants must have recovered from all radiation-related toxicities, and must not require corticosteroids. - Has received a live vaccine within 30 days prior to the first dose of study treatment. - In the investigator's judgment, has not recovered from toxicity or other complications from any major surgery prior to starting study treatment. - Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. - Has history or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at a dose exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization. - Has had an active malignancy (except locally advanced or metastatic UC) within the past 36 months. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded. - Has a history of prostate cancer (T2NXMX or lower with Gleason score =7) treated with definitive intent (surgically or with radiation therapy) =1 year prior to study entry is acceptable, provided that the participant is considered prostate cancer-free. - Has central nervous system (CNS) metastases, unless the participant has completed local therapy (e.g. whole brain radiation therapy, surgery, or radiosurgery) and has discontinued use of corticosteroids for this indication for =4 weeks before starting study treatment. Any signs (e.g. radiologic) or symptoms of CNS metastases must be stable for =4 weeks before starting study treatment. - Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e, with disease-modifying agents, corticosteroids, or immunosuppressive drugs). - Has a history of (non-infectious) pneumonitis that required systemic steroids, or current pneumonitis. - Has an active infection requiring systemic therapy. - Has a known history of human immunodeficiency virus (HIV) infection. - Has a known history of or is positive for active hepatitis B virus (HBV) or has active hepatitis C virus (HCV). - Has active tuberculosis (TB). - Is receiving hemodialysis. - Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab and lenvatinib/placebo. - Has had an allogeneic tissue/solid organ transplant. |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0577) | Berazategui | Buenos Aires |
| Argentina | Centro de Urología CDU ( Site 0590) | Buenos Aires | Caba |
| Argentina | Centro Medico Dra De Salvo ( Site 0593) | Buenos Aires | |
| Argentina | Instituto de Investigaciones Metabolicas ( Site 0589) | Buenos Aires | |
| Argentina | Instituto Medico Alexander Fleming ( Site 0578) | Buenos Aires | Caba |
| Argentina | CEMAIC ( Site 0581) | Cordoba | |
| Argentina | Centro Oncologico de Integracion Regional. COIR ( Site 0576) | Mendoza | |
| Argentina | Centro Oncológico de Rosario ( Site 0584) | Rosario | Santa Fe |
| Argentina | Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0585) | Viedma | Rio Negro |
| Australia | Monash Health ( Site 0160) | Clayton | Victoria |
| Australia | Peninsula Health Frankston Hospital ( Site 0153) | Frankston | Victoria |
| Australia | Austin Health-Austin Hospital ( Site 0154) | Heidelberg | Victoria |
| Australia | Macquarie University ( Site 0151) | North Ryde | New South Wales |
| Australia | Mater Misericordiae Ltd ( Site 0158) | South Brisbane | Queensland |
| Canada | Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0101) | Hamilton | Ontario |
| Canada | Lakeridge Health ( Site 0103) | Oshawa | Ontario |
| Canada | CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0104) | Quebec | |
| Canada | CIUSSS de l Estrie Centre Hospitalier Universitaire de Sherbrooke ( Site 0102) | Sherbrooke | Quebec |
| Canada | Sunnybrook Research Institute ( Site 0106) | Toronto | Ontario |
| China | Fifth Medical Center of CPLA General Hospital ( Site 0732) | Beijing | Beijing |
| China | Peking University First Hospital ( Site 0726) | Beijing | Beijing |
| China | Peking University Third Hospital ( Site 0727) | Beijing | Beijing |
| China | Hunan Cancer Hospital ( Site 0745) | Changsha | Hunan |
| China | Chongqing Cancer Hospital ( Site 0741) | Chongging | Chongqing |
| China | Sun Yat-Sen University Cancer Center ( Site 0752) | Guangdong | Guangdong |
| China | Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ( Site 0746) | Guangzhou | Guangdong |
| China | The First Affiliated Hospital of Guangzhou Medical University ( Site 0749) | Guangzhou | Guangdong |
| China | Second Affiliated Hospital, Zhejiang University ( Site 0734) | Hangzhou | Zhejiang |
| China | Zhejiang Provincial People's Hospital ( Site 0735) | Hangzhou | Zhejiang |
| China | Harbin Medical University Cancer Hospital ( Site 0750) | Harbin | Heilongjiang |
| China | Nanjing Drum Tower Hospital ( Site 0737) | Nanjing | Jiangsu |
| China | Fudan University Shanghai Cancer Center ( Site 0721) | Shanghai | Shanghai |
| China | Zhongshan Hospital Fudan University ( Site 0725) | Shanghai | Shanghai |
| China | Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0751) | Urumqi | Xinjiang |
| China | Hubei Cancer Hospital ( Site 0744) | Wuhan | Hubei |
| China | The First Affiliated Hospital of Xiamen University ( Site 0743) | Xiamen | Fujian |
| China | The First Affiliated Hospital of Xi an Jiaotong University ( Site 0738) | Xian | Shanxi |
| Denmark | Aalborg Universitets Hospital ( Site 0684) | Aalborg | Nordjylland |
| Denmark | Aarhus Universitets hospital ( Site 0683) | Aarhus N | Midtjylland |
| Denmark | Rigshospitalet ( Site 0680) | Copenhagen | Hovedstaden |
| Denmark | Herlev Hospital ( Site 0681) | Herlev | Hovedstaden |
| Denmark | Odense Universitetshospital ( Site 0682) | Odense | Syddanmark |
| France | Institut de Cancerologie de l Ouest Site Paul Papin ( Site 0236) | Angers | Maine-et-Loire |
| France | Centre Hospitalier de la Cote Basque ( Site 0239) | Bayonne | Pyrenees-Atlantiques |
| France | CHU de Bordeaux- Hopital Saint Andre ( Site 0235) | Bordeaux | Gironde |
| France | CHD Vendee-onco-hematologie ( Site 0251) | La Roche sur Yon | Vendee |
| France | Centre Leon Berard ( Site 0244) | Lyon | Rhone |
| France | Hopital de la Timone ( Site 0246) | Marseille | Bouches-du-Rhone |
| France | Centre de Cancerologie du Grand Montpellier ( Site 0249) | Montpellier | Languedoc-Roussillon |
| France | Centre D Oncologie de Gentilly ( Site 0240) | Nancy | Meurthe-et-Moselle |
| France | Institut Curie ( Site 0237) | Paris | |
| France | CHU Poitiers ( Site 0253) | Poitiers | Ain |
| France | CHIC Quimper ( Site 0245) | Quimper | Finistere |
| France | Centre Rene Gauducheau ICO ( Site 0250) | Saint Herblain | Loire-Atlantique |
| France | Institut de Cancerologie Strasbourg Europe ( Site 0232) | Strasbourg | Alsace |
| France | Clinique Pasteur ( Site 0252) | Tolouse | Haute-Garonne |
| France | Institut Gustave Roussy ( Site 0243) | Villejuif | Val-de-Marne |
| Germany | Universitaetsklinikum Essen ( Site 0274) | Essen | Nordrhein-Westfalen |
| Germany | Universitaetsmedizin Goettingen ( Site 0281) | Gottingen | Niedersachsen |
| Germany | Universitaetsklinikum Hamburg-Eppendorf ( Site 0282) | Hamburg | |
| Germany | Staedtisches Krankenhaus Kiel GmbH ( Site 0285) | Kiel | Schleswig-Holstein |
| Germany | Universitaetsklinikum Schleswig-Holstein-Campus Lubeck ( Site 0277) | Luebeck | Schleswig-Holstein |
| Germany | Universitaetsklinikum Giessen und Marburg GmbH ( Site 0284) | Marburg | Hessen |
| Germany | Helios Kliniken Schwerin GmbH ( Site 0278) | Schwerin | Mecklenburg-Vorpommern |
| Germany | Klinikum der Eberhard-Karls-Universitaet Tuebingen ( Site 0271) | Tuebingen | Baden-Wurttemberg |
| Hungary | Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 0509) | Budapest | |
| Hungary | Orszagos Onkologiai Intezet ( Site 0503) | Budapest | |
| Hungary | Uzsoki Utcai Korhaz ( Site 0508) | Budapest | |
| Hungary | Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0504) | Kaposvar | |
| Hungary | Bacs-Kiskun Megyei Korhaz ( Site 0510) | Kecskemet | Bacs-Kiskun |
| Hungary | Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce | Miskolc | Borsod-Abauj-Zemplen |
| Hungary | Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0507) | Szolnok | Jasz-Nagykun-Szolnok |
| Hungary | Markusovszky Egyetemi Oktatokorhaz ( Site 0502) | Szombathely | Vas |
| Israel | Ha Emek Medical Center ( Site 0560) | Afula | |
| Israel | Assuta Ashdod Public ( Site 0562) | Ashdod | |
| Israel | Rambam Medical Center ( Site 0552) | Haifa | |
| Israel | Hadassah Ein Kerem Medical Center ( Site 0558) | Jerusalem | |
| Israel | Shaare Zedek Medical Center ( Site 0559) | Jerusalem | |
| Israel | Meir Medical Center ( Site 0554) | Kfar Saba | |
| Israel | Rabin Medical Center ( Site 0553) | Petach-Tikwa | |
| Israel | Sheba Medical Center ( Site 0551) | Ramat Gan | |
| Israel | Sourasky Medical Center ( Site 0561) | Tel Aviv | |
| Israel | Assaf Harofeh Medical Center ( Site 0556) | Zerifin | |
| Italy | Centro di Riferimento Oncologico CRO ( Site 0304) | Aviano | Pordenone |
| Italy | Istituto Tumori Giovanni Paolo II ( Site 0306) | Bari | |
| Italy | Policlinico S. Orsola - Malpighi (Bologna) ( Site 0302) | Bologna | |
| Italy | Azienda Ospedaliera per l Emergenza Cannizzaro ( Site 0305) | Catania | |
| Italy | ASST Grande Ospedale Metropolitano Niguarda ( Site 0307) | Milano | Lombardia |
| Italy | Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0301) | Milano | |
| Italy | Ospedale San Raffaele-Oncologia Medica ( Site 0309) | Milano | Lombardia |
| Italy | Azienda Ospedaliera Santa Maria ( Site 0303) | Terni | |
| Italy | Ospedale Borgo Roma-Oncologia ( Site 0308) | Verona | |
| Japan | Akita University Hospital ( Site 0124) | Akita | |
| Japan | Chiba Cancer Center ( Site 0127) | Chiba | |
| Japan | Saitama Medical University International Medical Center ( Site 0125) | Hidaka | Saitama |
| Japan | Hirosaki University Hospital ( Site 0123) | Hirosaki | Aomori |
| Japan | Nara Medical University Hospital ( Site 0133) | Kashihara | Nara |
| Japan | National Cancer Center Hospital East ( Site 0128) | Kashiwa | Chiba |
| Japan | Nagasaki University Hospital ( Site 0136) | Nagasaki | |
| Japan | Osaka City University Hospital ( Site 0132) | Osaka | |
| Japan | Kitasato University Hospital ( Site 0129) | Sagamihara | Kanagawa |
| Japan | Sapporo Medical University Hospital ( Site 0122) | Sapporo | Hokkaido |
| Japan | Tokushima University Hospital ( Site 0134) | Tokushima | |
| Japan | Medical Hospital, Tokyo Medical And Dental University ( Site 0130) | Tokyo | |
| Japan | Ehime University Hospital ( Site 0137) | Toon | Ehime |
| Japan | University of Tsukuba Hospital ( Site 0126) | Tsukuba | Ibaraki |
| Japan | Yamaguchi University Hospital ( Site 0135) | Ube | Yamaguchi |
| Korea, Republic of | Chungnam National University Hospital ( Site 0195) | Daejeon | Taejon-Kwangyokshi |
| Korea, Republic of | National Cancer Center ( Site 0196) | Goyang-si | Kyonggi-do |
| Korea, Republic of | Chonnam National University Hwasun Hospital ( Site 0194) | Hwasun Gun | Jeonranamdo |
| Korea, Republic of | Korea University Anam Hospital ( Site 0197) | Seoul | |
| Korea, Republic of | Samsung Medical Center ( Site 0193) | Seoul | |
| Korea, Republic of | Seoul National University Hospital ( Site 0191) | Seoul | |
| Korea, Republic of | Severance Hospital ( Site 0192) | Seoul | |
| Korea, Republic of | Veterans Health Service Medical Center ( Site 0198) | Seoul | |
| Netherlands | Ziekenhuis Rijnstate ( Site 0342) | Arnhem | Gelderland |
| Netherlands | Amphia Ziekenhuis Breda ( Site 0331) | Breda | Noord-Brabant |
| Netherlands | Haga Ziekenhuis ( Site 0333) | Den Haag | Zuid-Holland |
| Netherlands | Deventer Ziekenhuis ( Site 0341) | Deventer | Overijssel |
| Netherlands | Maastricht Universitair Medisch Centrum - MUMC ( Site 0334) | Maastricht | Limburg |
| Netherlands | Erasmus MC ( Site 0332) | Rotterdam | Zuid-Holland |
| Netherlands | St. Antonius Ziekenhuis ( Site 0335) | Utrecht | |
| Netherlands | VieCuri Medisch Centrum ( Site 0340) | Venlo | Limburg |
| Poland | Szpital Miejski im. Jana Pawla II w Bielsku-Bialej ( Site 0542) | Bielsko-Biala | Slaskie |
| Poland | Europejskie Centrum Zdrowia Otwock ( Site 0532) | Otwock | Mazowieckie |
| Poland | Urologica Praktyka Lekarska Adam Marcheluk ( Site 0543) | Siedlce | Mazowieckie |
| Poland | Szpital Wojewodzki ( Site 1062) | Tarnow | Malopolskie |
| Poland | Luxmed Onkologia sp. z o. o. ( Site 0541) | Warszawa | Mazowieckie |
| Poland | Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 0535) | Wroclaw | Dolnoslaskie |
| Russian Federation | GBUZ Leningrad Regional Clinical Oncology Dispensary ( Site 0426) | Kuzmolovskiy Settlement | Leningradskaya Oblast |
| Russian Federation | Central Clinical Hospital with Polyclinic ( Site 0415) | Moscow | Moskva |
| Russian Federation | Medical Rehabilitation Center ( Site 0411) | Moscow | Moskva |
| Russian Federation | Russian Scientific Center of Roentgenoradiology ( Site 0424) | Moscow | Moskva |
| Russian Federation | Murmansk Regional Oncology Dispensary ( Site 0420) | Murmansk | Murmanskaya Oblast |
| Russian Federation | Volga District Medical Center Federal Medical and Biological Agency ( Site 0413) | Nizhny Novgorod | Nizhegorodskaya Oblast |
| Russian Federation | Omsk Clinical Oncology Dispensary ( Site 0418) | Omsk | Omskaya Oblast |
| Russian Federation | Clinical Hospital Saint Luka ( Site 0421) | Saint-Petersburg | Sankt-Peterburg |
| Russian Federation | Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0414) | Yaroslavl | Yaroslavskaya Oblast |
| Spain | Hospital Teresa Herrera - Chuac ( Site 0357) | A Coruna | La Coruna |
| Spain | Hospital Infanta Cristina ( Site 0355) | Badajoz | |
| Spain | Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 0351) | Badalona | Barcelona |
| Spain | Hospital General Universitari Vall d Hebron ( Site 0358) | Barcelona | |
| Spain | ICO L Hospitalet ( Site 0361) | Hospitalet de Llobregat | Barcelona |
| Spain | Hospital La Princesa ( Site 0862) | Madrid | |
| Spain | Hospital Universitario Gregorio Maranon ( Site 0352) | Madrid | |
| Spain | Hospital Universitario HM Sanchinarro ( Site 0356) | Madrid | Madrid, Comunidad De |
| Spain | Xarxa Assistencial Universitaria Manresa ( Site 0354) | Manresa | Barcelona |
| Taiwan | Kaohsiung Chang Gung Memorial Hospital ( Site 0217) | Kaohsiung | |
| Taiwan | Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 0216) | Kaoshiung | Kaohsiung |
| Taiwan | China Medical University Hospital ( Site 0213) | Taichung | |
| Taiwan | Taichung Veterans General Hospital ( Site 0214) | Taichung | |
| Taiwan | National Cheng Kung University Hospital ( Site 0215) | Tainan | |
| Taiwan | National Taiwan University Hospital ( Site 0211) | Taipei | |
| Taiwan | Taipei Veterans General Hospital ( Site 0212) | Taipei | |
| Turkey | Cukurova Universitesi Tip Fakultesi Balcali Hastanesi ( Site 0457) | Adana | |
| Turkey | Ankara Sehir Hastanesi ( Site 0455) | Ankara | |
| Turkey | Antalya Memorial Hospital Department of Medical Oncology ( Site 0461) | Antalya | |
| Turkey | Göztepe Prof. Dr. Süleyman Yalçin Sehir Hastanesi-oncology ( Site 0459) | Istanbul | |
| Turkey | Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0454) | Istanbul | |
| Turkey | Ege Universitesi Tulay Aktas Onkoloji Hastanesi ( Site 0462) | Izmir | |
| Turkey | Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0456) | Konya | |
| Turkey | Sakarya Universitesi Tip Fakultesi Arastirma Hastanesi ( Site 0460) | Sakarya | |
| United Kingdom | Kent and Canterbury Hospital ( Site 0390) | Canterbury | Kent |
| United Kingdom | Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 0378) | London | London, City Of |
| United Kingdom | Saint Bartholomew s Hospital - London ( Site 0386) | London | London, City Of |
| United Kingdom | University College London Hospital NHS Foundation Trust ( Site 0380) | London | London, City Of |
| United Kingdom | Nottingham University Hospital NHS Trust ( Site 0383) | Nottingham | |
| United Kingdom | Derriford Hospital ( Site 0388) | Plymouth | |
| United Kingdom | Royal Preston Hospital ( Site 0379) | Preston | Lancashire |
| United Kingdom | Queens Hospital-Purple Zone ( Site 0377) | Romford | Essex |
| United Kingdom | Weston Park Hospital ( Site 0387) | Sheffield | Derbyshire |
| United Kingdom | Lister Hospital ( Site 0376) | Stevenage | Hertfordshire |
| United Kingdom | Royal Stoke University Hospital Univ. Hosps of North Midlands NHST ( Site 0392) | Stoke-on-Trent | |
| United States | St. Peter's Hospital Cancer Care Center ( Site 0042) | Albany | New York |
| United States | Medical University of South Carolina-Hollings Cancer Center ( Site 0029) | Charleston | South Carolina |
| United States | University of Chicago ( Site 0039) | Chicago | Illinois |
| United States | Community Cancer Institute ( Site 0777) | Clovis | California |
| United States | Karmanos Cancer Institute ( Site 0712) | Detroit | Michigan |
| United States | Banner MD Anderson Cancer Center ( Site 0016) | Gilbert | Arizona |
| United States | Joliet Oncology Hematology ( Site 0091) | Joliet | Illinois |
| United States | Comprehensive Cancer Centers of Nevada ( Site 0005) | Las Vegas | Nevada |
| United States | Northwest Georgia Oncology Centers PC ( Site 0707) | Marietta | Georgia |
| United States | Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0002) | New York | New York |
| United States | University of California Irvine Medical Center ( Site 0078) | Orange | California |
| United States | Thomas Jefferson University Hospital ( Site 0051) | Philadelphia | Pennsylvania |
| United States | Quincy Medical Group ( Site 0022) | Quincy | Illinois |
| United States | Virginia Cancer Institute ( Site 0099) | Richmond | Virginia |
| United States | Mercy Hospital Saint Louis - David C. Pratt Cancer Center ( Site 0095) | Saint Louis | Missouri |
| United States | John Wayne Cancer Institute ( Site 0017) | Santa Monica | California |
| United States | New England Cancer Specialists ( Site 0047) | Scarborough | Maine |
| United States | Seattle Cancer Care Alliance ( Site 0003) | Seattle | Washington |
| United States | Cancer Care Northwest ( Site 0009) | Spokane | Washington |
| United States | Baylor Scott & White Medical Center - Temple ( Site 0706) | Temple | Texas |
| United States | Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0774) | Tulsa | Oklahoma |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC | Eisai Inc. |
United States, Argentina, Australia, Canada, China, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom,
Matsubara N, de Wit R, Balar AV, Siefker-Radtke AO, Zolnierek J, Csoszi T, Shin SJ, Park SH, Atduev V, Gumus M, Su YL, Karaca SB, Cutuli HJ, Sendur MAN, Shen L, O'Hara K, Okpara CE, Franco S, Moreno BH, Grivas P, Loriot Y. Pembrolizumab with or Without Le — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression-free Survival (PFS) | PFS was defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR), or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as =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 =5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by BICR per RECIST 1.1 is presented. Protocol-specified final analysis for this primary outcome measure was performed with an analysis data cut-off date of July-26-2021. | Up to ~25 months | |
| Primary | Overall Survival (OS) | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. Protocol-specified final analysis for this primary outcome measure was performed with an analysis data cut-off date of July-26-2021. | Up to ~25 months | |
| Secondary | Objective Response Rate (ORR) | ORR was defined as the percentage of participants who had a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR. The percentage of participants who experienced a CR or PR is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of July-26-2021. | Up to ~25 months | |
| Secondary | Duration of Response (DOR) | For participants who demonstrated a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as =20% increase in the sum of diameters of target lesions as well as an absolute increase of =5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. The DOR as assessed by BICR per RECIST 1.1 for participants who experienced a confirmed CR or PR is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of July-26-2021. | Up to ~25 months | |
| Secondary | Disease Control Rate (DCR) | DCR was defined at the percentage of participants who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: =20% increase in the sum of diameters of target lesions and an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD]. DCR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. The DCR as assessed by BICR per RECIST 1.1 is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of July-26-2021. | Up to ~25 months | |
| Secondary | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented. A higher score indicates a better outcome. | Baseline and Up to ~60 months | |
| Secondary | Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). TTD is defined as the time from baseline to the first onset of a =10-point negative change (decrease) from baseline in GHS (EORTC QLQ-C30 Item 29) & QoL (EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a =10-point negative change (decrease) from baseline in GHS and QoL combined score, will be presented. A longer TTD indicates a better outcome. | Up to ~60 months | |
| Secondary | Number of Participants Who Experience an Adverse Event (AE) | An AE was defined as 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. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of July-26-2021. | Up to ~25 months | |
| Secondary | Number of Participants Who Discontinue Study Treatment Due to an AE | An AE was defined as 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. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE is presented. Protocol-specified final analysis for this secondary outcome measure was performed with an analysis data cut-off date of July-26-2021. | Up to ~25 months |
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