Nonsquamous Non-small Cell Lung Cancer Clinical Trial
Official title:
A Phase 3 Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First-line Intervention in Participants With Metastatic Nonsquamous Non-small Cell Lung Cancer (LEAP-006)
| Verified date | September 2023 |
| 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 safety and efficacy of pemetrexed + platinum chemotherapy + pembrolizumab (MK-3475) with or without lenvatinib (MK-7902/E7080) as first-line intervention in adults with metastatic nonsquamous non-small cell lung cancer. The primary study hypotheses state that: 1) the combination of lenvatinib + platinum doublet chemotherapy + pembrolizumab prolongs Progression-free Survival (PFS) as assessed by blinded independent central review (BICR) per modified Response Evaluation Criteria in Solid Tumors version 1.1 (RESIST 1.1) compared to matching placebo + platinum doublet chemotherapy + pembrolizumab, and 2) the combination of lenvatinib + platinum doublet chemotherapy + pembrolizumab prolongs Overall Survival (OS) compared to matching placebo + platinum doublet chemotherapy + pembrolizumab.
| Status | Active, not recruiting |
| Enrollment | 761 |
| Est. completion date | June 21, 2024 |
| Est. primary completion date | August 11, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of Stage IV (American Joint Committee on Cancer [AJCC], nonsquamous NSCLC. - Confirmation that Epidermal Growth Factor Receptor (EGFR), ALK Receptor Tyrosine Kinase (ALK), or ROS1 Receptor Tyrosine Kinase (ROS1)-directed therapy is not indicated as primary treatment (documentation of absence of tumor-activating EGFR mutations AND absence of ALK and ROS1 gene rearrangements OR presence of a Kirsten Rat Sarcoma (KRAS) gene mutation). - Have measurable disease based on RECIST 1.1. Note: Lesions that appear measurable, but are situated in a previously irradiated area, can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation. - Provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (not previously irradiated). - Life expectancy of at least 3 months. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study intervention but before randomization. - Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed. - Male participants must agree for at least 7 days after the last dose of lenvatinib/matching placebo and up to 180 days after the last dose of chemotherapeutic agents to: 1. Refrain from donating sperm PLUS either: 2. Be abstinence from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR 3. Must agree to use contraception unless confirmed to be azoopsermic (vasectomized or secondary to medical cause) as detailed below: 1. Agree 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. Note: 7 days after lenvatinib/matching placebo is stopped, if the participant is on pembrolizumab only and is greater than 180 days post chemotherapy, no male contraception measures are needed. - Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. - Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1. Is not a WOCBP OR 2. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab and/or 30 days post-lenvatinib/matching placebo, and up to 180 days post last dose of chemotherapeutic agents, whichever occurs last. - Adequate organ function. - Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 mm Hg and no change in antihypertensive medications within 1 week prior to randomization. Note: Participants must not have a history of uncontrolled or poorly-controlled hypertension, defined as >150/90 mm Hg for >4 weeks despite standard medical management. Exclusion Criteria: - Known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable, and have not required steroids for at least 14 days prior to the first dose of study intervention. - History of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease. - Radiographic evidence of intratumoral caviations, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib-therapy. (In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta). - Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy. Note: The time requirement also does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers. - Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed. - Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention. - Has had allogeneic tissue/solid organ transplant. - Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority. - Known history of Hepatitis B. No testing for Hepatitis B or Hepatitis C is required unless mandated by the local health authority. - History of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral drug absorption. - Active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior to the first dose of study intervention. - Significant cardiovascular impairment within 12 months prior to the first dose of study intervention, including history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability. - Known history of active tuberculosis. - Active infection requiring systemic therapy. - Has not recovered adequately from any toxicity and/or complication from major surgery prior to the first dose of study intervention. - Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of lenvatinib or pembrolizumab, or as applicable, carboplatin, cisplatin, or pemetrexed. - A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. - Has preexisting =Grade 3 gastrointestinal or non-gastrointestinal fistula. - Received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC. Note: Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic NSCLC. - Received prior treatment with pembrolizumab or any other anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2 agent, with lenvatinib or any other receptor tyrosine kinase inhibitor (RTKi), or with an agent directed to another stimulatory or co-inhibitory T cell receptor. - Received radiotherapy within 14 days prior to the first dose of study intervention or received lung radiation therapy of >30 Gy within 6 months prior to the first dose of study intervention. Note: Participants must have recovered from all radiation-related toxicities to Grade =1, not required corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease. - Received systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of study intervention. - Received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: killed vaccines are allowed. - Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study intervention. - History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. - Left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO). |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0367) | Berazategui | Buenos Aires |
| Argentina | CEMIC ( Site 0370) | Buenos Aires | Caba |
| Argentina | Hospital Aleman ( Site 0368) | Buenos Aires | |
| Argentina | Instituto Medico Especializado Alexander Fleming ( Site 0369) | Buenos Aires | |
| Argentina | CEMAIC ( Site 0374) | Cordoba | |
| Argentina | Instituto de Investigaciones Clinicas Mar del Plata ( Site 0371) | Mar del Plata | Buenos Aires |
| Argentina | Sanatorio Parque ( Site 0365) | Rosario | Santa Fe |
| Argentina | CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0372) | San Juan | |
| Australia | Ballarat Health Services ( Site 0003) | Ballarat | Victoria |
| Australia | Blacktown Hospital Western Sydney Local Health District ( Site 0008) | Blacktown | New South Wales |
| Australia | Cairns Hospital ( Site 0002) | Cairns | Queensland |
| Australia | The Prince Charles Hospital ( Site 0010) | Chermside | Queensland |
| Australia | Port Macquarie Base Hospital ( Site 0001) | Port Macquarie | New South Wales |
| Australia | Chris OBrien Lifehouse ( Site 0006) | Sydney | New South Wales |
| Australia | Westmead Hospital ( Site 0009) | Sydney | New South Wales |
| Canada | Juravinski Cancer Centre ( Site 0407) | Hamilton | Ontario |
| Canada | Kingston Health Sciences Centre ( Site 0414) | Kingston | Ontario |
| Canada | Hopital Cite de la Sante de Laval ( Site 0400) | Laval | Quebec |
| Canada | Moncton Hospital - Horizon Health Network ( Site 0410) | Moncton | New Brunswick |
| Canada | CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0412) | Montreal | Quebec |
| Canada | Lakeridge Health ( Site 0406) | Oshawa | Ontario |
| Canada | CHU de Quebec-Universite Laval-Hotel Dieu de Quebec ( Site 0403) | Quebec | |
| Canada | Sault Area Hospital ( Site 0413) | Sault Ste Marie | Ontario |
| Canada | CIUSSS de la Mauricie et du Centre du Quebec ( Site 0408) | Trois-Rivieres | Quebec |
| Chile | Centro Oncologico Antofagasta ( Site 0386) | Antofagasta | |
| Chile | Bradford Hill Centro de Investigaciones Clinicas ( Site 0387) | Santiago | Region M. De Santiago |
| Chile | Fundacion Arturo Lopez Perez FALP ( Site 0383) | Santiago | Region M. De Santiago |
| Chile | OrlandiOncologia ( Site 0381) | Santiago | Region M. De Santiago |
| Chile | Pontificia Universidad Catolica de Chile ( Site 0382) | Santiago | Region M. De Santiago |
| Chile | Clinica Universidad Catolica del Maule ( Site 0385) | Talca | Maule |
| Chile | Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0380) | Temuco | Araucania |
| Chile | Oncocentro ( Site 0384) | Vina del Mar | Valparaiso |
| China | Beijing Cancer Hospital ( Site 0120) | Beijing | Beijing |
| China | Cancer Hospital Chinese Academy of Medical Science ( Site 0117) | Beijing | Beijing |
| China | Peking Union Medical College Hospital ( Site 0108) | Beijing | Beijing |
| China | Jilin Cancer Hospital ( Site 0115) | Changchun | Jilin |
| China | First Affiliated Hospital of The Third Military Medical University ( Site 0118) | Chongqing | Chongqing |
| China | The Second Hospital Affiliated to AMU ( Site 0119) | Chongqing | Chongqing |
| China | Fujian Provincial Cancer Hospital ( Site 0102) | Fuzhou | Fujian |
| China | Southern Medical University Nanfang Hospital ( Site 0121) | Guangzhou | Guangdong |
| China | The First Affiliated Hospital Zhejiang University ( Site 0109) | Hangzhou | Zhejiang |
| China | Zhejiang Cancer Hospital ( Site 0113) | Hangzhou | Zhejiang |
| China | The Third Affiliated Hospital of Harbin Medical University ( Site 0100) | Harbin | Heilongjiang |
| China | Shanghai Pulmonary Hospital ( Site 0101) | Shanghai | Shanghai |
| China | Zhongshan Hospital Fudan University ( Site 0103) | Shanghai | Shanghai |
| China | Tianjin Medical University Cancer Institute & Hospital ( Site 0111) | Tian Jin | Tianjin |
| China | Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0110) | Urumuqi | Xinjiang |
| China | The First Affiliated Hospital of Wenzhou Medical University ( Site 0124) | Wen Zhou | Zhejiang |
| China | Hubei Cancer Hospital ( Site 0122) | Wuhan | Hubei |
| China | Wuhan Union Hospital Cancer Center-Cancer Center ( Site 0123) | Wuhan | Hubei |
| China | Henan Cancer Hospital ( Site 0112) | Zhengzhou | Henan |
| France | Hopital Cardiologique Louis Pradel ( Site 0141) | Bron | Rhone-Alpes |
| France | Hopital Nord du Marseille ( Site 0147) | Marseille | Bouches-du-Rhone |
| France | Centre de Cancerologie du Grand Montpellier ( Site 0142) | Montpellier | Herault |
| France | Hopital Laennec ( Site 0146) | Nantes cedex 1 | Loire-Atlantique |
| France | Hopital Cochin ( Site 0140) | Paris | |
| France | Centre Paul Strauss ( Site 0144) | Strasbourg | Bas-Rhin |
| France | Hopital Foch ( Site 0145) | Suresnes | Hauts-de-Seine |
| France | Hopital Robert Schuman ( Site 0143) | Vantoux | Moselle |
| France | L'hopital Nord-Ouest - Centre Hospitalier de Villefranche sur Saone ( Site 0149) | Villefranche sur Saone | Rhone |
| Germany | Uniklinik RWTH Aachen ( Site 0160) | Aachen | Nordrhein-Westfalen |
| Germany | Klinikum Esslingen GmbH ( Site 0164) | Esslingen | Baden-Wurttemberg |
| Germany | Krankenhaus Nordwest ( Site 0169) | Frankfurt | Hessen |
| Germany | LungenClinic Grosshansdorf GmbH ( Site 0171) | Grosshansdorf | Schleswig-Holstein |
| Germany | Krankenhaus Martha Maria Halle-Doelau ( Site 0166) | Halle | Sachsen-Anhalt |
| Germany | Hamato-Onkologie Hamburg Prof. Laack und Partner ( Site 0161) | Hamburg | |
| Germany | Universitaetsklinikum des Saarlandes ( Site 0165) | Homburg | Saarland |
| Germany | Pius Hospital Oldenburg ( Site 0170) | Oldenburg | Niedersachsen |
| Israel | Soroka Medical Center ( Site 0222) | Beer Sheva | |
| Israel | Rambam Medical Center ( Site 0223) | Haifa | |
| Israel | Shaare Zedek Medical Center-Oncology ( Site 0229) | Jerusalem | |
| Israel | Meir Medical Center ( Site 0221) | Kfar Saba | |
| Israel | Holy Family Hospital ( Site 0228) | Nazareth | |
| Israel | Rabin Medical Center ( Site 0224) | Petah Tikva | |
| Israel | Sheba Medical Center ( Site 0220) | Ramat Gan | |
| Israel | Sourasky Medical Center ( Site 0225) | Tel Aviv | |
| Israel | Shamir Medical Center-Assaf Harofeh ( Site 0227) | Zerifin | |
| Japan | Osaka Habikino Medical Center ( Site 0020) | Habikino | Osaka |
| Japan | Kansai Medical University Hospital ( Site 0022) | Hirakata | Osaka |
| Japan | Kanazawa University Hospital ( Site 0018) | Kanazawa | Ishikawa |
| Japan | National Cancer Center Hospital East ( Site 0024) | Kashiwa | Chiba |
| Japan | National Hospital Organization Nagoya Medical Center ( Site 0017) | Nagoya | Aichi |
| Japan | Niigata Cancer Center Hospital ( Site 0019) | Niigata | |
| Japan | National Cancer Center Hospital ( Site 0026) | Tokyo | |
| Japan | The Cancer Institute Hospital of JFCR ( Site 0021) | Tokyo | |
| Japan | Tokyo Metropolitan Komagome Hospital ( Site 0015) | Tokyo | |
| Japan | Fujita Health University Hospital ( Site 0016) | Toyoake | Aichi |
| Japan | Wakayama Medical University Hospital ( Site 0025) | Wakayama | |
| Korea, Republic of | Chungbuk National University Hospital ( Site 0062) | Cheongju si | Chungbuk |
| Korea, Republic of | National Cancer Center ( Site 0061) | Goyang-si | Kyonggi-do |
| Korea, Republic of | The Catholic University of Korea St. Vincent s Hospital ( Site 0064) | Gyeonggi-do | Kyonggi-do |
| Korea, Republic of | Severance Hospital Yonsei University Health System ( Site 0063) | Seoul | |
| New Zealand | Auckland City Hospital ( Site 0011) | Auckland | |
| New Zealand | Tauranga Hospital ( Site 0004) | Tauranga | Bay Of Plenty |
| Poland | Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 0601) | Bydgoszcz | Kujawsko-pomorskie |
| Poland | Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0602) | Koszalin | Zachodniopomorskie |
| Poland | Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii ( Site 0613) | Lodz | Lodzkie |
| Poland | Pleszewskie Centrum Medyczne w Pleszewie Sp. z o.o. ( Site 0615) | Pleszew | Wielkopolskie |
| Poland | MED-POLONIA Sp. z o.o. ( Site 0609) | Poznan | Wielkopolskie |
| Poland | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0603) | Warszawa | Mazowieckie |
| Russian Federation | Moscow Regional Oncological Dispensary ( Site 0274) | Balashikha | Moskovskaya Oblast |
| Russian Federation | SAHI Republican Clinical Oncological Dispensary of the MoH of RT ( Site 0261) | Kazan | Tatarstan, Respublika |
| Russian Federation | Central Clinical Hospital with outpatient Clinic ( Site 0262) | Moscow | Moskva |
| Russian Federation | City Clinical Hospital 1 na. NI. Pirogov ( Site 0270) | Moscow | Moskva |
| Russian Federation | FSAI Treatment and Rehabilitation Centre of the MoH and SD of RF ( Site 0264) | Moscow | Moskva |
| Russian Federation | National Medical Research Radiology Centre ( Site 0260) | Moscow | Moskva |
| Russian Federation | Nizhniy Novgorod Region Oncology Dispensary ( Site 0272) | Nizhniy Novgorod | Nizhegorodskaya Oblast |
| Russian Federation | Omsk Clinical Oncology Dispensary ( Site 0267) | Omsk | Omskaya Oblast |
| Russian Federation | Leningrad Regional Oncology Center ( Site 0271) | Saint Petersburg | Leningradskaya Oblast |
| Russian Federation | Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0269) | Saint Petersburg | Sankt-Peterburg |
| Russian Federation | First Pavlov State Medical University of Saint Petersburg-Department of Oncology ( Site 0273) | Saint-Petersburg | Sankt-Peterburg |
| Spain | Complejo Hospitalario Universitario A Coruna ( Site 0239) | A Coruna | La Coruna |
| Spain | Hospital General Universitario de Alicante ( Site 0240) | Alicante | |
| Spain | Hospital Santa Creu i Sant Pau ( Site 0241) | Barcelona | |
| Spain | ICO L Hospitalet ( Site 0234) | Hospitalet de Llobregat | Barcelona |
| Spain | Hospital Universitario Insular de Gran Canaria ( Site 0244) | Las Palmas de Gran Canaria | Las Palmas |
| Spain | Hospital Clinico San Carlos ( Site 0235) | Madrid | |
| Spain | Hospital General Universitario Gregorio Maranon ( Site 0237) | Madrid | |
| Spain | Hospital Universitario La Paz ( Site 0236) | Madrid | |
| Spain | Complejo Hospitalario de Malaga ( Site 0238) | Malaga | |
| Spain | Hospital General Universitario de Valencia ( Site 0231) | Valencia | Valenciana, Comunitat |
| Spain | Hospital Universitario La Fe ( Site 0233) | Valencia | Valenciana, Comunitat |
| Spain | Hospital Universitario Miguel Servet ( Site 0242) | Zaragoza | |
| Turkey | Cukurova Universitesi Tip Fakultesi Balcali Hastanesi ( Site 0314) | Adana | |
| Turkey | Ankara Sehir Hastanesi ( Site 0323) | Ankara | |
| Turkey | Ankara Universitesi Tip Fakultesi. ( Site 0317) | Ankara | |
| Turkey | Hacettepe Universitesi Tip Fakultesi ( Site 0316) | Ankara | |
| Turkey | Göztepe Prof. Dr. Süleyman Yalçin Sehir Hastanesi-oncology ( Site 0310) | Istanbul | |
| Turkey | Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0312) | Istanbul | |
| Turkey | Ege Universitesi Tip Fakultesi ( Site 0313) | Izmir | |
| Turkey | Inonu Universitesi Medical Fakultesi ( Site 0318) | Malatya | |
| United Kingdom | Aberdeen Royal Infirmary ( Site 0288) | Aberdeen | Scotland |
| United Kingdom | Cambridge University Hospitals NHS Trust ( Site 0293) | Cambridge | Cambridgeshire |
| United Kingdom | Leeds Teaching Hospital NHS Trust. St. James University Hospital ( Site 0276) | Leeds | |
| United Kingdom | Leicester Royal Infirmary ( Site 0284) | Leicester | |
| United Kingdom | Guys and St Thomas NHS Foundation Trust ( Site 0280) | London | London, City Of |
| United Kingdom | North Middlesex University Hospital NHS Trust ( Site 0291) | London | London, City Of |
| United Kingdom | St Georges University Hospitals NHS Foundation Trust. ( Site 0292) | London | London, City Of |
| United Kingdom | Christie NHS Foundation Trust ( Site 0275) | Manchester | |
| United Kingdom | Nottingham City Hospital Campus ( Site 0287) | Nottingham | |
| United Kingdom | The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0286) | Wirral | |
| United States | Good Samaritan Hospital Corvallis ( Site 0521) | Corvallis | Oregon |
| United States | Parkland Health & Hospital System ( Site 0576) | Dallas | Texas |
| United States | UT Southwestern Medical Center ( Site 0558) | Dallas | Texas |
| United States | Henry Ford Health System ( Site 0563) | Detroit | Michigan |
| United States | Sanford Health Roger Maris Cancer Center ( Site 0533) | Fargo | North Dakota |
| United States | Holy Cross Hospital ( Site 0512) | Fort Lauderdale | Florida |
| United States | West Cancer Center - East Campus ( Site 0544) | Germantown | Tennessee |
| United States | Broome Oncology, LLC ( Site 0562) | Johnson City | New York |
| United States | Saint Lukes Cancer Institute ( Site 0541) | Kansas City | Missouri |
| United States | West Virginia University ( Site 0526) | Morgantown | West Virginia |
| United States | El Camino Hospital Cancer Center ( Site 0529) | Mountain View | California |
| United States | Yale University ( Site 0519) | New Haven | Connecticut |
| United States | Stephenson Cancer Center ( Site 0504) | Oklahoma City | Oklahoma |
| United States | Mercy Health-Paducah Medical Oncology and Hematology ( Site 0570) | Paducah | Kentucky |
| United States | Thomas Jefferson University Hospital ( Site 0548) | Philadelphia | Pennsylvania |
| United States | Utah Cancer Specialists ( Site 0523) | Salt Lake City | Utah |
| United States | Abington Hospital - Asplundh Cancer Center ( Site 0575) | Willow Grove | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC | Eisai Inc. |
United States, Argentina, Australia, Canada, Chile, China, France, Germany, Israel, Japan, Korea, Republic of, New Zealand, Poland, Russian Federation, Spain, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Part 1: Number of Participants with a Dose-limiting Toxicity | Dose-limiting toxicity using Common Terminology Criteria for Adverse Events v4.0 for grading, is defined as any of the following hematologic toxicities: 1) Grade 4 neutropenia, 2) Grade 3 or 4 febrile neutropenia, 3) thrombocytopenia <25,000 cells/mm^3 associated with bleeding and/or which requires platelet transfusion, or any of the following non-hematologic toxicities: 4) any other Grade 4 or 5 toxicity, 5) Grade 3 toxicities lasting >3 days (exclusions apply), 6) Grade 3 hypertension not controlled by medication, 7) Grade 3 or above gastrointestinal perforation, 8) Grade 3 or above wound dehiscence requiring medical or surgical intervention, 9) any grade thromboembolic event, or 10) any Grade 3 nonhematologic laboratory value if medical intervention is required or the abnormality leads to hospitalization. | Cycle 1; each cycle is 21 days (up to 21 days) | |
| Primary | Part 1: Number of Participants with One or More Adverse Events | An adverse event is 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. The number of participants who experience one of more adverse events during Part 1 of this study will be presented. | Through 90 days post last dose of study treatment (Up to approximately 27 months) | |
| Primary | Number of Participants With Study Intervention Discontinuations Due to Adverse Events | An adverse event is 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. The number of participants who discontinue study medication due to and adverse event during Part 1 of this study will be presented. | Up to approximately 24 months | |
| Primary | Part 2: Progression-free Survival (PFS) as Assessed by BICR according to RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ | PFS is defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) 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 =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. Note: The appearance of one or more new lesions is also considered PD. PFS as assessed per modified RECIST 1.1 will be presented. | Up to approximately 36 months | |
| Primary | Part 2: Overall Survival (OS) | OS is defined as the time from randomization to the time of death from any cause. OS will be presented. | Up to approximately 47 months | |
| Secondary | Part 2: Objective Response Rate (ORR) as Assessed by BICR according to RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ | 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. ORR as assessed per modified RECIST 1.1 will be presented. | Up to approximately 19 months | |
| Secondary | Part 2; Duration of Response (DOR) as Assessed by BICR according to RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ | For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until PD 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, or death from any cause, PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. Note: The appearance of one or more new lesions is also considered PD. DOR as assessed per modified RECIST 1.1 will be presented. | Up to approximately 19 months | |
| Secondary | Part 2: Number of Participants with One or More Adverse Events | An adverse event is 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. The number of participants who experience one of more adverse events during Part 2 of this study will be presented. | Up to approximately 27 months | |
| Secondary | Part 2: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event | An adverse event is 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. The number of participants who discontinue study treatment during Part 2 of this study will be presented. | Up to approximately 24 months | |
| Secondary | Part 2: Change from Baseline in Global Health Status/Quality of Life (QoL); Cough; Chest Pain; Dyspnea; and Physical Functioning | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The EORTC Quality of Life Questionnaire and Lung Cancer Module 13 (QLQ-LC13) is a supplemental lung cancer-specific module used in combination with QLQ-C30. The change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life (EORTC QLQ-C30 Items 29 and 30); Cough (EORTC QLQ-LC13 Item 31); Chest Pain (EORTC QLQ-LC13 Item 40); Dyspnea (EORTC QLQ-C30 Item 8); and Physical Functioning (EORTC QLQ-C30 Items 1-5). | Baseline (Cycle 1 Day 1) and at designated timepoints up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) | |
| Secondary | Part 2: Time to True Deterioration as Assessed by Change from Baseline in Global Health Status/Quality of Life; Cough; Chest Pain; Dyspnea; and Physical Functioning | The time to true deterioration defined as the time from baseline to the first onset of a =10-point deterioration from baseline with confirmation by the subsequent visit of a =10-point deterioration from baseline in Global Health Status/Quality of Life (EORTC QLQ-C30 Items 29 and 30); cough (EORTC QLQ-LC13 Item 31); chest pain (EORTC QLQ-LC13 Item 40); dyspnea (EORTC QLQ-C30 Item 8); and physical functioning (EORTC QLQ-C30 Items 1-5). | Baseline (Cycle 1 Day 1) and at designated timepoints up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) | |
| Secondary | Time to True Deterioration in the Composite Endpoint (Combination of Cough, Chest Pain, or Dyspnea) | Time to true deterioration in the composite endpoint (combination of cough [QLQ-LC13 Item 31], chest pain [QLQ-LC13 Item 40], or dyspnea [QLQ-C30 Item 8]). Defined as the time to first onset of a =10-point deterioration from baseline in any one of 3 scale items with confirmation by the subsequent visit of a =10-point deterioration from baseline in the same scale as the first onset. | Baseline (Cycle 1 Day 1) and at designated timepoints up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) |
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