Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) in Adults With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Treatment-naïve Nonsmall Cell Lung Cancer (NSCLC) (MK-7902-007/E7080-G000-314/LEAP-007)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03829332
Collaborator
Eisai Inc. (Industry)
623
162
2
59.9
3.8
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) in treatment-naïve adults with no prior systemic therapy for their metastatic non-small cell lung cancer (NSCLC) whose tumors have a programmed cell death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) greater than or equal to 1%.
The primary study hypotheses are that: 1) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1); and 2) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Overall Survival (OS).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
With Amendment 6 (effective date: 15-Sep-2021), active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded. Participants will discontinue lenvatinib and placebo, and participants who remain on treatment will receive open-label pembrolizumab only.
Study Design
Study Type:
Interventional
Actual Enrollment
:
623 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) in Participants With Treatment-naïve, Metastatic Nonsmall Cell Lung Cancer (NSCLC) Whose Tumors Have a Tumor Proportion Score (TPS) Greater Than or Equal to 1% (LEAP-007)
Actual Study Start Date
:
Mar 13, 2019
Actual Primary Completion Date
:
May 19, 2021
Anticipated Study Completion Date
:
Mar 8, 2024
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pembrolizumab + Lenvatinib Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Lenvatinib
oral capsule
Other Names:
|
| Active Comparator: Pembrolizumab + Placebo Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Placebo for lenvatinib
oral capsule
|
Outcome Measures
Primary Outcome Measures
- Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 25 months]
PFS was 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 occurred 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 demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Data are from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by blinded independent central review (BICR) per RECIST 1.1 is presented.
- Overall Survival (OS) [Up to approximately 25 months]
OS was defined as the time from date of randomization to date of death from any cause. OS is presented.
Secondary Outcome Measures
- Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 25 months]
ORR was 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. ORR as assessed by BICR per RECIST 1.1 is presented.
- Number of Participants Who Experience an Adverse Event (AE) [Through 90 days post last dose of study treatment (Up to approximately 27 months)]
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 who experience an AE will be presented.
- Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [Through last dose of study treatment (Up to approximately 24 months)]
The number of participants who discontinue study treatment due to an AE will be presented.
- Change From Baseline in Global Health Status (GHS) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] Item 29) Score [Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)]
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "How would you rate your overall health 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) score will be presented. A higher score indicates a better overall GHS.
- Change From Baseline in Quality of Life (QoL) (EORTC QLQ-C30 Item 30) Score [Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)]
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question " 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 QoL (EORTC QLQ-C30 Item 30) score will be presented. A higher score indicates a better overall QoL.
- Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score [Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)]
The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in cough (EORTC QLQ-LC13 Item 31) score will be presented. A lower score indicates a better outcome.
- Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score [Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)]
The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score will be presented. A lower score indicates a better outcome.
- Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score [Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)]
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score will be presented. A lower score indicates a better outcome.
- Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score [Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)]
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented. A higher score indicates a better quality of life.
- Time to True Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS) (EORTC QLQ-C30 Item 29) Score [Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)]
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) 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 score, will be presented. A longer TTD indicates a better outcome.
- Time to True Deterioration (TTD) Based on Change From Baseline in Quality of Life (QoL) (EORTC QLQ-C30 Item 30) Score [Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)]
TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in QoL (EORTC QLQ-C30 Item 30) 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 QoL score, will be presented. A longer TTD indicates a better outcome.
- Time to True Deterioration (TTD) Based on Change From Baseline in the Composite Endpoint of Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), or Dyspnea (EORTC QLQ-C30 Item 8) [Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)]
TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in the composite endpoint of cough (QLQ-LC13 item 31), chest pain (QLQ-LC13 item 40), or dyspnea (QLQ-C30 Item 8). 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 the composite endpoint of cough, chest pain or dyspnea, will be presented. A longer TTD indicates a better outcome.
- Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score [Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)]
TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in physical functioning (EORTC QLQ-C30 Items 1-5) 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 physical functioning score, will be presented.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Has a histologically or cytologically confirmed diagnosis of NSCLC.
-
Has Stage IV NSCLC (American Joint Committee on Cancer [AJCC 8th edition]).
-
Has measurable disease based on RECIST 1.1.
-
Has tumor tissue that demonstrates programmed cell death-ligand 1 (PD-L1) expression in ≥1% of tumor cells (Tumor Proportion Score [TPS] ≥1%) as assessed by immunohistochemistry (IHC) 22C3 pharmDx assay (Dako North America, Inc.) at a central laboratory.
-
Has a life expectancy of ≥3 months.
-
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study treatment but before randomization.
-
Male participants must agree to the following during the treatment period and for ≥7 days after the last dose of lenvatinib/matching placebo: 1) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR 2) Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause).
-
Female participants are eligible to participate if not pregnant or breastfeeding, and ≥1 of the following applies: 1) Is not a woman of child-bearing potential (WOCBP), OR
- Is a WOCBP and is using a highly effective contraceptive method that has a low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period and for ≥120 days post pembrolizumab or ≥30 days post lenvatinib/matching placebo, whichever occurs last.
-
Has 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 before randomization.
-
Has adequate organ function.
Exclusion Criteria:
-
Has known untreated central nervous system metastases and/or carcinomatous meningitis.
-
Has active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior to the first dose of study intervention.
-
Has radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel.
-
Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for ≥3 years since initiation of that therapy. (Note: The time requirement 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.)
-
Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
-
Has had an allogeneic tissue/solid organ transplant.
-
Has a known history of human immunodeficiency virus (HIV) infection.
-
Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
-
Has a known history of hepatitis B or known active hepatitis C virus infection.
-
Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption.
-
Has significant cardiovascular impairment within 12 months of the first dose of study treatment, such as a history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident/stroke, or cardiac arrhythmia associated with hemodynamic instability.
-
Has not recovered adequately from any toxicity and/or complications from major surgery before starting study treatment.
-
Has a known history of active tuberculosis (TB).
-
Has an active infection requiring systemic therapy.
-
Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity or intolerance to any component of lenvatinib or pembrolizumab.
-
Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC.
-
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 co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137]) or has received lenvatinib as monotherapy or in combination with anti- programmed cell death protein (anti-PD-1) agents.
-
Has received radiotherapy within 14 days before the first dose of study treatment or received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. (Note: Participants must have recovered from all radiation-related toxicities to ≤Grade 1, not require corticosteroids, and not have had radiation pneumonitis.)
-
Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days before the first dose of study treatment.
-
Is receiving systemic steroid therapy (doses >10 mg daily of prednisone equivalent) within 7 days before the first dose of study treatment.
-
Has received a live or attenuated vaccine within 30 days before the first dose of study treatment.
-
Has had major surgery within 3 weeks prior to first dose of study treatment
-
Has pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Alaska Clinical Research Center ( Site 0511) | Anchorage | Alaska | United States | 99503 |
| 2 | Ironwood Cancer & Research Centers ( Site 0541) | Chandler | Arizona | United States | 85224 |
| 3 | CBCC Global Research, Inc. ( Site 0532) | Bakersfield | California | United States | 93309 |
| 4 | Scripps Cancer Center ( Site 0521) | La Jolla | California | United States | 92037 |
| 5 | Florida Hospital ( Site 0526) | Orlando | Florida | United States | 32803 |
| 6 | Northwest Georgia Oncology Centers PC ( Site 0518) | Marietta | Georgia | United States | 30060 |
| 7 | Illinois Cancer Care, PC ( Site 0557) | Peoria | Illinois | United States | 61615 |
| 8 | Parkview Cancer Center ( Site 0542) | Fort Wayne | Indiana | United States | 46845 |
| 9 | University of Kentucky School of Medicine & Hospitals ( Site 0517) | Lexington | Kentucky | United States | 40536 |
| 10 | Anne Arundel Medical Center Oncology and Hematology ( Site 0514) | Annapolis | Maryland | United States | 21401 |
| 11 | Munson Medical Center ( Site 0512) | Traverse City | Michigan | United States | 49684 |
| 12 | Park Nicollet Frauenshuh Cancer Center ( Site 0554) | Saint Louis Park | Minnesota | United States | 55426 |
| 13 | University of Missouri Health Care ( Site 0555) | Columbia | Missouri | United States | 65212 |
| 14 | Billings Clinic Cancer Center ( Site 0508) | Billings | Montana | United States | 59101 |
| 15 | Cone Health Cancer Center at Alamance Regional ( Site 0527) | Greensboro | North Carolina | United States | 27403 |
| 16 | Genesis Cancer Care Center ( Site 0559) | Zanesville | Ohio | United States | 43701 |
| 17 | Oregon Health Sciences University ( Site 0544) | Portland | Oregon | United States | 97239 |
| 18 | Central Texas Veterans Healthcare System ( Site 0533) | Temple | Texas | United States | 76504 |
| 19 | Orange Health Services ( Site 0002) | Orange | New South Wales | Australia | 2800 |
| 20 | Wollongong Private Hospital ( Site 0005) | Wollongong | New South Wales | Australia | 2500 |
| 21 | The Prince Charles Hospital ( Site 0011) | Chermside | Queensland | Australia | 4032 |
| 22 | Ballarat Oncology and Haematology Services ( Site 0008) | Wendouree | Victoria | Australia | 3355 |
| 23 | St John of God Murdoch Medical Clinic ( Site 0001) | Perth | Western Australia | Australia | 6150 |
| 24 | Cross Cancer Institute ( Site 0400) | Edmonton | Alberta | Canada | T6G 1Z2 |
| 25 | Lions Gate Hospital ( Site 0407) | North Vancouver | British Columbia | Canada | V7L 2L7 |
| 26 | William Osler Health System (Brampton Civic Hospital) ( Site 0402) | Brampton | Ontario | Canada | L6R 3J7 |
| 27 | Windsor Regional Cancer Program ( Site 0404) | Windsor | Ontario | Canada | N8W 2X3 |
| 28 | McGill University Health Centre ( Site 0418) | Montreal | Quebec | Canada | H4A 3J1 |
| 29 | Beijing Chest Hospital Capital Medical University ( Site 0111) | Beijing | Anhui | China | 101149 |
| 30 | Anhui Provincial Hospital ( Site 0108) | Hefei | Anhui | China | 230001 |
| 31 | The First Affiliated Hospital of Anhui Medical University ( Site 0113) | Hefei | Anhui | China | 230088 |
| 32 | Peking Union Medical College Hospital ( Site 0105) | Beijing | Beijing | China | 100006 |
| 33 | Beijing Cancer Hospital ( Site 0102) | Beijing | Beijing | China | 100036 |
| 34 | Xiangya Hospital of Central South University ( Site 0115) | Changsha | Hunan | China | 410008 |
| 35 | Hunan Cancer Hospital ( Site 0104) | Changsha | Hunan | China | 410013 |
| 36 | Jiangsu Cancer Hospital ( Site 0101) | Nanjing | Jiangsu | China | 210009 |
| 37 | The First Hospital of Jilin University ( Site 0110) | Chang chun | Jilin | China | 130021 |
| 38 | Zhongshan Hospital Fudan University ( Site 0100) | Shanghai | Shanghai | China | 200433 |
| 39 | Shanghai Chest Hospital ( Site 0112) | Shanghai | Shanghai | China | 230000 |
| 40 | 1st Affil Hosp of Med College of Xi'an Jiaotong University ( Site 0103) | XiAn | Shanxi | China | 710061 |
| 41 | West China Hospital of Sichuan University ( Site 0117) | Chengdu | Sichuan | China | 510115 |
| 42 | The First Affiliated Hospital Zhejiang University ( Site 0106) | Hangzhou | Zhejiang | China | 310003 |
| 43 | Hangzhou First People's Hospital ( Site 0109) | Hangzhou | Zhejiang | China | 310006 |
| 44 | 2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0114) | Hangzhou | Zhejiang | China | 310009 |
| 45 | Zhejiang Cancer Hospital ( Site 0116) | Hangzhou | Zhejiang | China | 310022 |
| 46 | Hospital General de Medellin Luz Castro de Gutierrez ( Site 0368) | Medellin | Antioquia | Colombia | 050015 |
| 47 | Fundacion Centro de Investigacion Clinica CIC ( Site 0366) | Medellin | Antioquia | Colombia | 050021 |
| 48 | Biomelab S A S ( Site 0365) | Barranquilla | Atlantico | Colombia | 080002 |
| 49 | Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0374) | Valledupar | Cesar | Colombia | 200001 |
| 50 | Oncomedica S.A. ( Site 0372) | Monteria | Cordoba | Colombia | 230002 |
| 51 | Centro Medico Imbanaco de Cali S.A ( Site 0369) | Cali | Valle Del Cauca | Colombia | 760023 |
| 52 | AS Ida-Tallinna Keskhaigla ( Site 0161) | Tallinn | Harjumaa | Estonia | 11312 |
| 53 | SA Pohja-Eesti Regionaalhaigla ( Site 0162) | Tallin | Harjumaa | Estonia | 13419 |
| 54 | SA Tartu Ulikooli Kliinikum ( Site 0160) | Tartu | Tartumaa | Estonia | 50406 |
| 55 | CHU Jean Minjoz ( Site 0167) | Besancon | Doubs | France | 25000 |
| 56 | Institut Curie - Centre Rene Huguenin ( Site 0181) | Saint-Cloud | Hauts-de-Seine | France | 92210 |
| 57 | ICM Val D Auerelle ( Site 0177) | Montpellier | Herault | France | 34090 |
| 58 | CHU de Grenoble - Hopital Michallon ( Site 0169) | La Tronche | Isere | France | 38700 |
| 59 | Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0185) | Saint Herblain | Loire-Atlantique | France | 44805 |
| 60 | Centre Hospitalier de la Cote Basque ( Site 0173) | Bayonne | Pyrenees-Atlantiques | France | 64109 |
| 61 | CHU de Rouen ( Site 0174) | Rouen | Seine-Maritime | France | 76000 |
| 62 | CHU Amiens Sud ( Site 0182) | Amiens | Somme | France | 80054 |
| 63 | Centre hospitalier Toulon Sainte-Musse ( Site 0172) | Toulon | Var | France | 83056 |
| 64 | Institut Curie ( Site 0166) | Paris | France | 75248 | |
| 65 | Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0207) | Gyula | Bekes | Hungary | 5700 |
| 66 | Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz ( Site 0202) | Miskolc | Borsod-Abauj-Zemplen | Hungary | 3529 |
| 67 | CRU Hungary KFT ( Site 0209) | Miskolc | Borsod-Abauj-Zemplen | Hungary | 3529 |
| 68 | Petz Aladar Megyei Oktato Korhaz ( Site 0213) | Gyor | Gyor-Moson-Sopron | Hungary | 9024 |
| 69 | Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0203) | Szolnok | Jasz-Nagykun-Szolnok | Hungary | 5000 |
| 70 | Tudogyogyintezet Torokbalint ( Site 0205) | Torokbalint | Pest | Hungary | 2045 |
| 71 | Semmelweis Egyetem ( Site 0210) | Budapest | Hungary | 1083 | |
| 72 | Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0217) | Kaposvar | Hungary | 7400 | |
| 73 | Bnei Zion Medical Center ( Site 0227) | Haifa | Heifa | Israel | 3339419 |
| 74 | Sheba Medical Center ( Site 0220) | Ramat Gan | Tel Aviv | Israel | 5266202 |
| 75 | Soroka Medical Center ( Site 0222) | Beer Sheva | Israel | 8457108 | |
| 76 | Rambam Medical Center ( Site 0223) | Haifa | Israel | 3109601 | |
| 77 | Meir Medical Center ( Site 0221) | Kfar-Saba | Israel | 4428132 | |
| 78 | Rabin Medical Center ( Site 0224) | Petah Tikva | Israel | 4941492 | |
| 79 | Sourasky Medical Center ( Site 0225) | Tel Aviv | Israel | 6423906 | |
| 80 | Barzilai Medical Center ( Site 0226) | Ashkelon | Ḥeifā | Israel | 7830604 |
| 81 | Azienda Ospedaliera S. Giovanni Addolorata-Oncologia Medica ( Site 0233) | Roma | Lazio | Italy | 00185 |
| 82 | Presidio Ospedaliero San Vincenzo ( Site 0231) | Taormina | Messina | Italy | 98039 |
| 83 | Centro di Riferimento Oncologico CRO ( Site 0235) | Aviano | Pordenone | Italy | 33081 |
| 84 | Azienda Ospedaliera San Giuseppe Moscati ( Site 0234) | Avellino | Italy | 83100 | |
| 85 | Universita Magna Grecia ( Site 0230) | Catanzaro | Italy | 88100 | |
| 86 | A.O. Universitaria Careggi ( Site 0236) | Firenze | Italy | 50134 | |
| 87 | Ospedale Santa Maria delle Croci ( Site 0232) | Ravenna | Italy | 48121 | |
| 88 | Policlinico Gemelli di Roma ( Site 0237) | Roma | Italy | 00168 | |
| 89 | Aichi Cancer Center Hospital ( Site 0018) | Nagoya | Aichi | Japan | 464-8681 |
| 90 | Kurume University Hospital ( Site 0025) | Kurume | Fukuoka | Japan | 830-0011 |
| 91 | Hyogo Cancer Center ( Site 0021) | Akashi | Hyogo | Japan | 673-8558 |
| 92 | Kanagawa Cardiovascular and Respiratory Center ( Site 0026) | Yokohama | Kanagawa | Japan | 236-0051 |
| 93 | Kanagawa Cancer Center ( Site 0023) | Yokohama | Kanagawa | Japan | 241-8515 |
| 94 | Miyagi Cancer Center ( Site 0028) | Natori | Miyagi | Japan | 981-1293 |
| 95 | Sendai Kousei Hospital ( Site 0022) | Sendai | Miyagi | Japan | 980-0873 |
| 96 | Kindai University Hospital ( Site 0017) | Osakasayama | Osaka | Japan | 589-8511 |
| 97 | National Hospital Organization Kinki-chuo Chest Medical Center ( Site 0027) | Sakai | Osaka | Japan | 591-8555 |
| 98 | National Hospital Organization Kyushu Medical Center ( Site 0015) | Fukuoka | Japan | 810-8563 | |
| 99 | Kyushu University Hospital ( Site 0030) | Fukuoka | Japan | 812-8582 | |
| 100 | Okayama University Hospital ( Site 0020) | Okayama | Japan | 700-8558 | |
| 101 | Osaka International Cancer Institute ( Site 0019) | Osaka | Japan | 541-8567 | |
| 102 | Toranomon Hospital ( Site 0016) | Tokyo | Japan | 105-8470 | |
| 103 | Juntendo University Hospital ( Site 0029) | Tokyo | Japan | 113-8431 | |
| 104 | Nippon Medical School Hospital ( Site 0024) | Tokyo | Japan | 113-8603 | |
| 105 | Chungbuk National University Hospital ( Site 0079) | Cheongju si | Chungbuk | Korea, Republic of | 28644 |
| 106 | Seoul National University Bundang Hospital ( Site 0075) | Seongnam-si | Kyonggi-do | Korea, Republic of | 13620 |
| 107 | Ulsan University Hospital ( Site 0077) | Ulsan | Ulsan-Kwangyokshi | Korea, Republic of | 44033 |
| 108 | Asan Medical Center ( Site 0076) | Seoul | Korea, Republic of | 05505 | |
| 109 | SMG-SNU Boramae Medical Center ( Site 0078) | Seoul | Korea, Republic of | 07061 | |
| 110 | Hospital Tengku Ampuan Afzan ( Site 0062) | Kuantan | Pahang | Malaysia | 25100 |
| 111 | Hospital Pulau Pinang. ( Site 0065) | Georgetown | Pulau Pinang | Malaysia | 10990 |
| 112 | Sarawak General Hospital ( Site 0064) | Kuching | Sarawak | Malaysia | 93586 |
| 113 | Beacon Hospital Sdn Bhd ( Site 0067) | Petaling Jaya | Selangor | Malaysia | 46050 |
| 114 | Institut Kanser Negara - National Cancer Institute ( Site 0063) | Putrajaya | Wilayah Persekutuan Putrajaya | Malaysia | 62250 |
| 115 | University Malaya Medical Centre ( Site 0061) | Kuala Lumpur | Malaysia | 59100 | |
| 116 | Gleneagles Penang ( Site 0066) | Pulau Pinang | Malaysia | 10050 | |
| 117 | Medica Sur S.A.B de C.V. ( Site 0384) | Mexico City | Distrito Federal | Mexico | 14050 |
| 118 | Consultorios de Medicina Especializada del Sector Privado ( Site 0388) | Guadalajara | Jalisco | Mexico | 44680 |
| 119 | Centro de Estudios de Investigacion Metabolicos y Cardiovasculares ( Site 0381) | Madero | Tamaulipas | Mexico | 89440 |
| 120 | Instituto Nacional de Cancerologia. ( Site 0382) | Mexico City | Mexico | 14080 | |
| 121 | Oaxaca Site Management Organization SC ( Site 0389) | Oaxaca | Mexico | 68000 | |
| 122 | SPZOZ USK nr 1 im. Norberta Barlickiego UM w Lodzi ( Site 0256) | Lodz | Lodzkie | Poland | 99-153 |
| 123 | Szpital Uniwersytecki im. Karola Marcinkowskiego ( Site 0247) | Zielona Gora | Lubuskie | Poland | 65-046 |
| 124 | Krakowski Szpital Specjalistyczny im Jana Pawla II ( Site 0253) | Krakow | Malopolskie | Poland | 31-202 |
| 125 | Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 0243) | Krakow | Malopolskie | Poland | 31-826 |
| 126 | Centrum Medyczne Pratia Ostroleka ( Site 0242) | Ostroleka | Mazowieckie | Poland | 07-410 |
| 127 | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0252) | Warszawa | Mazowieckie | Poland | 02-781 |
| 128 | Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 0250) | Przemysl | Podkarpackie | Poland | 37-700 |
| 129 | Ars Medical Sp. z o.o. ( Site 0254) | Pila | Wielkopolskie | Poland | 64-920 |
| 130 | Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 0262) | Ufa | Baskortostan, Respublika | Russian Federation | 450054 |
| 131 | Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0266) | Krasnoyarsk | Krasnoyarskiy Kray | Russian Federation | 660133 |
| 132 | SBHI Samara Regional Clinical Oncology Dispensary ( Site 0265) | Samara | Samarskaya Oblast | Russian Federation | 443031 |
| 133 | SBHI Leningrad Regional Clinical Hospital ( Site 0263) | Saint Petersburg | Sankt-Peterburg | Russian Federation | 194291 |
| 134 | Railway Hospital of OJSC ( Site 0268) | Saint Petersburg | Sankt-Peterburg | Russian Federation | 195271 |
| 135 | City Clinical Oncology Center ( Site 0260) | Saint Petersburg | Sankt-Peterburg | Russian Federation | 198255 |
| 136 | Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0269) | Kazan | Tatarstan, Respublika | Russian Federation | 420029 |
| 137 | National Taiwan University Hospital Hsin-Chu Branch ( Site 0087) | Hsinchu | Taiwan | 300 | |
| 138 | Taipei Medical University Shuang Ho Hospital ( Site 0090) | New Taipei | Taiwan | 235 | |
| 139 | National Cheng Kung University Hospital ( Site 0086) | Tainan | Taiwan | 70457 | |
| 140 | National Taiwan University Hospital ( Site 0088) | Taipei | Taiwan | 10002 | |
| 141 | Koo Foundation Sun Yat-Sen Cancer Center ( Site 0091) | Taipei | Taiwan | 112 | |
| 142 | Taipei Veterans General Hospital ( Site 0089) | Taipei | Taiwan | 112 | |
| 143 | Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 0321) | Konya | Adana | Turkey | 42080 |
| 144 | Gulhane Egitim ve Arastirma Hastanesi ( Site 0316) | Ankara | Turkey | 06010 | |
| 145 | Abdurrahman Yurtaslan Onkoloji Hastanesi ( Site 0318) | Ankara | Turkey | 06200 | |
| 146 | Baskent Universitesi Ankara Hastanesi ( Site 0319) | Ankara | Turkey | 06490 | |
| 147 | Antalya Memorial Hospital Department of Medical Oncology ( Site 0324) | Antalya | Turkey | 07020 | |
| 148 | Akdeniz Universitesi Tip Fakultesi ( Site 0322) | Antalya | Turkey | 07070 | |
| 149 | Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi ( Site 0314) | Izmir | Turkey | 35340 | |
| 150 | Sakarya Universitesi Egitim ve Arastirma Hastanesi ( Site 0323) | Sakarya | Turkey | 54290 | |
| 151 | Samsun Medical Park Hastanesi ( Site 0320) | Samsun | Turkey | 55200 | |
| 152 | Cherkasy Regional Hospital ( Site 0336) | Cherkasy | Cherkaska Oblast | Ukraine | 18009 |
| 153 | City Clinical Hosp.4 of DCC ( Site 0338) | Dnipro | Dnipropetrovska Oblast | Ukraine | 49102 |
| 154 | MI Precarpathian Clinical Oncology Center ( Site 0346) | Ivano-Frankivsk | Ivano-Frankivska Oblast | Ukraine | 76018 |
| 155 | Regional Centre of Oncology-Thoracic organs ( Site 0337) | Kharkiv | Kharkivska Oblast | Ukraine | 61070 |
| 156 | Ukranian Center of TomoTherapy ( Site 0344) | Kropyvnytskiy | Kirovohradska Oblast | Ukraine | 25011 |
| 157 | Medical Center Verum ( Site 0334) | Kyiv | Kyivska Oblast | Ukraine | 03039 |
| 158 | Kyiv City Clinical Oncology Centre ( Site 0339) | Kyiv | Kyivska Oblast | Ukraine | 03115 |
| 159 | Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 0331) | Kyiv | Kyivska Oblast | Ukraine | 03126 |
| 160 | Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 0341) | Lviv | Lvivska Oblast | Ukraine | 79031 |
| 161 | MI Odessa Regional Oncological Centre ( Site 0333) | Odesa | Odeska Oblast | Ukraine | 65055 |
| 162 | Podillya Regional Center of Oncology ( Site 0343) | Vinnytsia | Vinnytska Oblast | Ukraine | 21029 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
- Eisai Inc.
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT03829332
Other Study ID Numbers:
- 7902-007
- MK-7902-007
- E7080-G000-314
- LEAP-007
- 194670
- 2018-003794-98
First Posted:
Feb 4, 2019
Last Update Posted:
Jun 2, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Merck Sharp & Dohme LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Of the 623 total participants randomized in the MK-7902-007 global study, 80 were also randomized in the China extension study for MK-7902-007 (NCT04676412). |
|---|---|
| Pre-assignment Detail | Of the 623 randomized participants, 621 received treatment. As of the 19-May-2021 database cut-off, 329 participants were ongoing in the study for long-term safety and survival follow-up. |
| Arm/Group Title | Pembrolizumab + Lenvatinib | Pembrolizumab + Placebo |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. | Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. |
| Period Title: Overall Study | ||
| STARTED | 309 | 314 |
| Treated | 309 | 312 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 309 | 314 |
Baseline Characteristics
| Arm/Group Title | Pembrolizumab + Lenvatinib | Pembrolizumab + Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. | Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. | Total of all reporting groups |
| Overall Participants | 309 | 314 | 623 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
64.6
(9.6)
|
65.4
(8.8)
|
65.0
(9.2)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
79
25.6%
|
90
28.7%
|
169
27.1%
|
| Male |
230
74.4%
|
224
71.3%
|
454
72.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
32
10.4%
|
30
9.6%
|
62
10%
|
| Not Hispanic or Latino |
266
86.1%
|
269
85.7%
|
535
85.9%
|
| Unknown or Not Reported |
11
3.6%
|
15
4.8%
|
26
4.2%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
7
2.3%
|
3
1%
|
10
1.6%
|
| Asian |
103
33.3%
|
104
33.1%
|
207
33.2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
1
0.3%
|
1
0.2%
|
| White |
188
60.8%
|
193
61.5%
|
381
61.2%
|
| More than one race |
3
1%
|
3
1%
|
6
1%
|
| Unknown or Not Reported |
8
2.6%
|
10
3.2%
|
18
2.9%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants) | |||
| ECOG = 0 |
110
35.6%
|
108
34.4%
|
218
35%
|
| ECOG = 1 |
199
64.4%
|
206
65.6%
|
405
65%
|
| Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline (Count of Participants) | |||
| TPS = 1-49% |
172
55.7%
|
175
55.7%
|
347
55.7%
|
| TPS = ≥ 50% |
137
44.3%
|
139
44.3%
|
276
44.3%
|
| Geographic Region (Count of Participants) | |||
| East Asia |
103
33.3%
|
104
33.1%
|
207
33.2%
|
| Non-East Asia |
206
66.7%
|
210
66.9%
|
416
66.8%
|
Outcome Measures
| Title | Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
|---|---|
| Description | PFS was 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 occurred 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 demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Data are from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by blinded independent central review (BICR) per RECIST 1.1 is presented. |
| Time Frame | Up to approximately 25 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all randomized participants. |
| Arm/Group Title | Pembrolizumab + Lenvatinib | Pembrolizumab + Placebo |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. | Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. |
| Measure Participants | 309 | 314 |
| Median (95% Confidence Interval) [Months] |
6.6
|
4.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab + Lenvatinib, Pembrolizumab + Placebo |
|---|---|---|
| Comments | Comparison based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and Baseline PD-L1 Status (1% to 49% versus >=50%). | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.00624 |
| Comments | ||
| Method | Stratified Log Rank | |
| Comments | One-sided p-value based on log-rank test stratified by ECOG performance status, geographic region of the enrolling site, and baseline PD-L1 status. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.78 | |
| Confidence Interval |
(2-Sided) 95% 0.64 to 0.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time from date of randomization to date of death from any cause. OS is presented. |
| Time Frame | Up to approximately 25 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all randomized participants. |
| Arm/Group Title | Pembrolizumab + Lenvatinib | Pembrolizumab + Placebo |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. | Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. |
| Measure Participants | 309 | 314 |
| Median (95% Confidence Interval) [Months] |
14.1
|
16.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab + Lenvatinib, Pembrolizumab + Placebo |
|---|---|---|
| Comments | Comparison based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and Baseline PD-L1 Status (1% to 49% versus >=50%). | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.79744 |
| Comments | ||
| Method | Stratified Log Rank | |
| Comments | One-sided p-value based on log-rank test stratified by ECOG performance status, geographic region of the enrolling site, and baseline PD-L1 status. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.10 | |
| Confidence Interval |
(2-Sided) 95% 0.87 to 1.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
|---|---|
| Description | ORR was 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. ORR as assessed by BICR per RECIST 1.1 is presented. |
| Time Frame | Up to approximately 25 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population consisted of all randomized participants. |
| Arm/Group Title | Pembrolizumab + Lenvatinib | Pembrolizumab + Placebo |
|---|---|---|
| Arm/Group Description | Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. | Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. |
| Measure Participants | 309 | 314 |
| Number (95% Confidence Interval) [Percentage of Participants] |
40.5
13.1%
|
27.7
8.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab + Lenvatinib, Pembrolizumab + Placebo |
|---|---|---|
| Comments | Comparison based on Miettinen & Nurminen method stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and Baseline PD-L1 Status (1% to 49% versus >=50%). | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.00037 |
| Comments | ||
| Method | Stratified Miettinen & Nurminen | |
| Comments | One-sided p-value for testing. H0: difference in percent = 0 versus H1: difference in percent > 0. | |
| Method of Estimation | Estimation Parameter | Percent Difference |
| Estimated Value | 12.8 | |
| Confidence Interval |
(2-Sided) 95% 5.4 to 20.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants Who Experience an Adverse Event (AE) |
|---|---|
| Description | 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 who experience an AE will be presented. |
| Time Frame | Through 90 days post last dose of study treatment (Up to approximately 27 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) |
|---|---|
| Description | The number of participants who discontinue study treatment due to an AE will be presented. |
| Time Frame | Through last dose of study treatment (Up to approximately 24 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Change From Baseline in Global Health Status (GHS) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] Item 29) Score |
|---|---|
| Description | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "How would you rate your overall health 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) score will be presented. A higher score indicates a better overall GHS. |
| Time Frame | Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Change From Baseline in Quality of Life (QoL) (EORTC QLQ-C30 Item 30) Score |
|---|---|
| Description | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question " 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 QoL (EORTC QLQ-C30 Item 30) score will be presented. A higher score indicates a better overall QoL. |
| Time Frame | Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score |
|---|---|
| Description | The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in cough (EORTC QLQ-LC13 Item 31) score will be presented. A lower score indicates a better outcome. |
| Time Frame | Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score |
|---|---|
| Description | The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score will be presented. A lower score indicates a better outcome. |
| Time Frame | Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score |
|---|---|
| Description | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score will be presented. A lower score indicates a better outcome. |
| Time Frame | Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score |
|---|---|
| Description | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented. A higher score indicates a better quality of life. |
| Time Frame | Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to True Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS) (EORTC QLQ-C30 Item 29) Score |
|---|---|
| Description | 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) 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 score, will be presented. A longer TTD indicates a better outcome. |
| Time Frame | Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to True Deterioration (TTD) Based on Change From Baseline in Quality of Life (QoL) (EORTC QLQ-C30 Item 30) Score |
|---|---|
| Description | TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in QoL (EORTC QLQ-C30 Item 30) 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 QoL score, will be presented. A longer TTD indicates a better outcome. |
| Time Frame | Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to True Deterioration (TTD) Based on Change From Baseline in the Composite Endpoint of Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), or Dyspnea (EORTC QLQ-C30 Item 8) |
|---|---|
| Description | TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in the composite endpoint of cough (QLQ-LC13 item 31), chest pain (QLQ-LC13 item 40), or dyspnea (QLQ-C30 Item 8). 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 the composite endpoint of cough, chest pain or dyspnea, will be presented. A longer TTD indicates a better outcome. |
| Time Frame | Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score |
|---|---|
| Description | TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in physical functioning (EORTC QLQ-C30 Items 1-5) 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 physical functioning score, will be presented. |
| Time Frame | Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | Up to approximately 25 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All-Cause Mortality includes all randomized participants. Serious and Other adverse events (AEs) includes all randomized participants who received ≥1 dose of study drug. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study treatment. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" & "Disease progression" not related to study treatment are excluded as AEs. Data are reported by treatment received. | |||
| Arm/Group Title | Lenvatinib + Pembrolizumab | Placebo + Pembrolizumab | ||
| Arm/Group Description | Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. | Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. | ||
All Cause Mortality |
||||
| Lenvatinib + Pembrolizumab | Placebo + Pembrolizumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 149/309 (48.2%) | 137/314 (43.6%) | ||
Serious Adverse Events |
||||
| Lenvatinib + Pembrolizumab | Placebo + Pembrolizumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 175/309 (56.6%) | 106/312 (34%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Cardiac disorders | ||||
| Acute myocardial infarction | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Atrial fibrillation | 3/309 (1%) | 3 | 3/312 (1%) | 3 |
| Atrial flutter | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Atrioventricular block complete | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Bradycardia | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Cardiac arrest | 2/309 (0.6%) | 2 | 1/312 (0.3%) | 1 |
| Cardiac failure | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Cardiac failure acute | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Cardiac failure congestive | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Cardiac ventricular thrombosis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Cardio-respiratory arrest | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Immune-mediated myocarditis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Myocardial infarction | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Myocarditis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pericardial effusion | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Pericardial haemorrhage | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Congenital, familial and genetic disorders | ||||
| Tracheo-oesophageal fistula | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Endocrine disorders | ||||
| Adrenal insufficiency | 2/309 (0.6%) | 2 | 2/312 (0.6%) | 2 |
| Hyperthyroidism | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hypophysitis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hypothyroidism | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Inappropriate antidiuretic hormone secretion | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Thyroiditis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal wall haematoma | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Anal fistula | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Ascites | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Colitis | 3/309 (1%) | 3 | 1/312 (0.3%) | 2 |
| Diarrhoea | 4/309 (1.3%) | 4 | 0/312 (0%) | 0 |
| Dysphagia | 1/309 (0.3%) | 1 | 2/312 (0.6%) | 2 |
| Enterocolitis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Gastric ulcer perforation | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Gastrointestinal haemorrhage | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Ileus | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Intestinal pseudo-obstruction | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Intra-abdominal fluid collection | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Large intestinal ulcer | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Melaena | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Oral cavity fistula | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pancreatitis | 4/309 (1.3%) | 5 | 0/312 (0%) | 0 |
| Peptic ulcer | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Rectal haemorrhage | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Stomatitis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| General disorders | ||||
| Asthenia | 4/309 (1.3%) | 4 | 0/312 (0%) | 0 |
| Axillary pain | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Chest discomfort | 2/309 (0.6%) | 2 | 0/312 (0%) | 0 |
| Chest pain | 2/309 (0.6%) | 2 | 1/312 (0.3%) | 1 |
| Death | 11/309 (3.6%) | 11 | 1/312 (0.3%) | 1 |
| Fatigue | 5/309 (1.6%) | 5 | 2/312 (0.6%) | 2 |
| General physical health deterioration | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Malaise | 2/309 (0.6%) | 2 | 0/312 (0%) | 0 |
| Multiple organ dysfunction syndrome | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Oedema peripheral | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Pain | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pyrexia | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Strangulated hernia | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Hepatobiliary disorders | ||||
| Cholangitis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Cholecystitis | 4/309 (1.3%) | 4 | 0/312 (0%) | 0 |
| Cholecystitis acute | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Cholelithiasis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Hepatitis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Hepatitis toxic | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Immune-mediated hepatitis | 2/309 (0.6%) | 2 | 1/312 (0.3%) | 1 |
| Portal hypertension | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Infections and infestations | ||||
| Abscess jaw | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Bronchitis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| COVID-19 | 1/309 (0.3%) | 1 | 2/312 (0.6%) | 2 |
| COVID-19 pneumonia | 4/309 (1.3%) | 4 | 3/312 (1%) | 4 |
| Clostridium difficile colitis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Empyema | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Gangrene | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Hepatitis B | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Infection | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Influenza | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Lower respiratory tract infection | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Lung abscess | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Meningitis aseptic | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Nasopharyngitis | 0/309 (0%) | 0 | 2/312 (0.6%) | 2 |
| Pleural infection | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pneumocystis jirovecii pneumonia | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Pneumonia | 28/309 (9.1%) | 31 | 16/312 (5.1%) | 18 |
| Pneumonia bacterial | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pneumonia fungal | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pneumonia pseudomonal | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Sepsis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Septic shock | 2/309 (0.6%) | 2 | 0/312 (0%) | 0 |
| Sinusitis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Upper respiratory tract infection | 3/309 (1%) | 3 | 0/312 (0%) | 0 |
| Urinary tract infection | 3/309 (1%) | 3 | 0/312 (0%) | 0 |
| Urosepsis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Wound infection | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Acetabulum fracture | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Compression fracture | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Femur fracture | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Intentional overdose | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Lumbar vertebral fracture | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Post procedural complication | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Spinal fracture | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Upper limb fracture | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase increased | 3/309 (1%) | 3 | 1/312 (0.3%) | 1 |
| Amylase increased | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Aspartate aminotransferase increased | 3/309 (1%) | 3 | 1/312 (0.3%) | 1 |
| Blood alkaline phosphatase increased | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Blood bilirubin increased | 0/309 (0%) | 0 | 2/312 (0.6%) | 2 |
| Blood creatinine increased | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Coagulation time prolonged | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Electrocardiogram QT prolonged | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Electrocardiogram ST segment elevation | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Lipase increased | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 7/309 (2.3%) | 7 | 0/312 (0%) | 0 |
| Dehydration | 4/309 (1.3%) | 4 | 1/312 (0.3%) | 1 |
| Diabetes mellitus | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hypercalcaemia | 0/309 (0%) | 0 | 2/312 (0.6%) | 2 |
| Hypocalcaemia | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hypoglycaemia | 2/309 (0.6%) | 2 | 0/312 (0%) | 0 |
| Hypokalaemia | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Hyponatraemia | 1/309 (0.3%) | 1 | 2/312 (0.6%) | 2 |
| Hypophagia | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Malnutrition | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/309 (0.3%) | 3 | 0/312 (0%) | 0 |
| Arthritis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Connective tissue disorder | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Groin pain | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Intervertebral disc protrusion | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Muscular weakness | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Myalgia | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Myositis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Neck pain | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Pathological fracture | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Rotator cuff syndrome | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Soft tissue mass | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Bladder cancer | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Cancer pain | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Keratoacanthoma | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Prostate cancer | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Skin angiosarcoma | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Tumour haemorrhage | 2/309 (0.6%) | 2 | 0/312 (0%) | 0 |
| Tumour necrosis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Nervous system disorders | ||||
| Altered state of consciousness | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Cerebral haemorrhage | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Cerebral infarction | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Cerebrovascular accident | 2/309 (0.6%) | 2 | 3/312 (1%) | 3 |
| Demyelination | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Epilepsy | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Haemorrhagic stroke | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hypersomnia | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Loss of consciousness | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Nervous system disorder | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Peripheral sensory neuropathy | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Posterior reversible encephalopathy syndrome | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Presyncope | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Spinal cord compression | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Transient ischaemic attack | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Psychiatric disorders | ||||
| Confusional state | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Delirium | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 2/309 (0.6%) | 2 | 3/312 (1%) | 3 |
| Renal impairment | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Tubulointerstitial nephritis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Urinary retention | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Urinary tract obstruction | 0/309 (0%) | 0 | 1/312 (0.3%) | 2 |
| Reproductive system and breast disorders | ||||
| Prostatomegaly | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Atelectasis | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Bronchial fistula | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Bronchospasm | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Chronic obstructive pulmonary disease | 2/309 (0.6%) | 2 | 5/312 (1.6%) | 5 |
| Dyspnoea | 2/309 (0.6%) | 2 | 2/312 (0.6%) | 2 |
| Epistaxis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Haemoptysis | 9/309 (2.9%) | 9 | 1/312 (0.3%) | 1 |
| Immune-mediated lung disease | 4/309 (1.3%) | 4 | 5/312 (1.6%) | 5 |
| Interstitial lung disease | 2/309 (0.6%) | 2 | 1/312 (0.3%) | 1 |
| Oesophagobronchial fistula | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Organising pneumonia | 2/309 (0.6%) | 4 | 0/312 (0%) | 0 |
| Pharyngeal inflammation | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Pleural effusion | 2/309 (0.6%) | 2 | 6/312 (1.9%) | 7 |
| Pneumonitis | 6/309 (1.9%) | 6 | 2/312 (0.6%) | 2 |
| Pneumothorax | 7/309 (2.3%) | 7 | 1/312 (0.3%) | 1 |
| Pulmonary embolism | 6/309 (1.9%) | 6 | 7/312 (2.2%) | 7 |
| Pulmonary haemorrhage | 3/309 (1%) | 3 | 1/312 (0.3%) | 1 |
| Pulmonary oedema | 1/309 (0.3%) | 1 | 1/312 (0.3%) | 1 |
| Respiratory distress | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Respiratory failure | 2/309 (0.6%) | 2 | 1/312 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Dermatosis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Drug eruption | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Immune-mediated dermatitis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Palmar-plantar erythrodysaesthesia syndrome | 2/309 (0.6%) | 2 | 0/312 (0%) | 0 |
| Rash | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Red man syndrome | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Skin lesion inflammation | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Skin ulcer | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Stevens-Johnson syndrome | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Subcutaneous emphysema | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Vascular disorders | ||||
| Accelerated hypertension | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Embolism | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Embolism arterial | 0/309 (0%) | 0 | 2/312 (0.6%) | 2 |
| Hypertension | 2/309 (0.6%) | 2 | 0/312 (0%) | 0 |
| Hypertensive crisis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hypertensive emergency | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Hypotension | 2/309 (0.6%) | 2 | 0/312 (0%) | 0 |
| Orthostatic hypotension | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Peripheral arterial occlusive disease | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Peripheral artery stenosis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Peripheral ischaemia | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Shock | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Thrombosis | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
| Vasculitis | 1/309 (0.3%) | 1 | 0/312 (0%) | 0 |
| Venous thrombosis limb | 0/309 (0%) | 0 | 1/312 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Lenvatinib + Pembrolizumab | Placebo + Pembrolizumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 292/309 (94.5%) | 269/312 (86.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 50/309 (16.2%) | 67 | 63/312 (20.2%) | 79 |
| Endocrine disorders | ||||
| Hyperthyroidism | 29/309 (9.4%) | 31 | 20/312 (6.4%) | 20 |
| Hypothyroidism | 124/309 (40.1%) | 153 | 31/312 (9.9%) | 32 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 24/309 (7.8%) | 28 | 5/312 (1.6%) | 5 |
| Abdominal pain upper | 23/309 (7.4%) | 26 | 10/312 (3.2%) | 10 |
| Constipation | 33/309 (10.7%) | 38 | 41/312 (13.1%) | 47 |
| Diarrhoea | 99/309 (32%) | 182 | 36/312 (11.5%) | 56 |
| Nausea | 65/309 (21%) | 110 | 40/312 (12.8%) | 74 |
| Stomatitis | 48/309 (15.5%) | 64 | 11/312 (3.5%) | 11 |
| Vomiting | 32/309 (10.4%) | 51 | 16/312 (5.1%) | 25 |
| General disorders | ||||
| Asthenia | 53/309 (17.2%) | 77 | 31/312 (9.9%) | 34 |
| Chest pain | 18/309 (5.8%) | 21 | 15/312 (4.8%) | 15 |
| Fatigue | 43/309 (13.9%) | 55 | 33/312 (10.6%) | 36 |
| Oedema peripheral | 25/309 (8.1%) | 35 | 18/312 (5.8%) | 19 |
| Pyrexia | 29/309 (9.4%) | 36 | 28/312 (9%) | 36 |
| Infections and infestations | ||||
| Pneumonia | 21/309 (6.8%) | 22 | 11/312 (3.5%) | 12 |
| Urinary tract infection | 23/309 (7.4%) | 30 | 15/312 (4.8%) | 19 |
| Investigations | ||||
| Alanine aminotransferase increased | 53/309 (17.2%) | 66 | 28/312 (9%) | 35 |
| Amylase increased | 24/309 (7.8%) | 32 | 9/312 (2.9%) | 10 |
| Aspartate aminotransferase increased | 52/309 (16.8%) | 72 | 28/312 (9%) | 37 |
| Blood alkaline phosphatase increased | 31/309 (10%) | 38 | 17/312 (5.4%) | 24 |
| Blood creatinine increased | 21/309 (6.8%) | 24 | 18/312 (5.8%) | 20 |
| Blood thyroid stimulating hormone increased | 24/309 (7.8%) | 29 | 7/312 (2.2%) | 9 |
| Lipase increased | 26/309 (8.4%) | 42 | 14/312 (4.5%) | 17 |
| Platelet count decreased | 31/309 (10%) | 42 | 7/312 (2.2%) | 10 |
| Weight decreased | 74/309 (23.9%) | 86 | 25/312 (8%) | 27 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 76/309 (24.6%) | 88 | 48/312 (15.4%) | 52 |
| Hyperglycaemia | 22/309 (7.1%) | 29 | 20/312 (6.4%) | 24 |
| Hypoalbuminaemia | 30/309 (9.7%) | 34 | 19/312 (6.1%) | 23 |
| Hypocalcaemia | 20/309 (6.5%) | 27 | 9/312 (2.9%) | 9 |
| Hypokalaemia | 24/309 (7.8%) | 29 | 21/312 (6.7%) | 25 |
| Hyponatraemia | 37/309 (12%) | 48 | 20/312 (6.4%) | 24 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 36/309 (11.7%) | 45 | 29/312 (9.3%) | 39 |
| Back pain | 23/309 (7.4%) | 25 | 25/312 (8%) | 28 |
| Pain in extremity | 20/309 (6.5%) | 23 | 14/312 (4.5%) | 16 |
| Nervous system disorders | ||||
| Dizziness | 17/309 (5.5%) | 21 | 7/312 (2.2%) | 7 |
| Headache | 28/309 (9.1%) | 39 | 12/312 (3.8%) | 12 |
| Psychiatric disorders | ||||
| Insomnia | 16/309 (5.2%) | 17 | 12/312 (3.8%) | 12 |
| Renal and urinary disorders | ||||
| Haematuria | 22/309 (7.1%) | 29 | 15/312 (4.8%) | 19 |
| Proteinuria | 99/309 (32%) | 157 | 34/312 (10.9%) | 48 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 24/309 (7.8%) | 30 | 21/312 (6.7%) | 22 |
| Dysphonia | 25/309 (8.1%) | 28 | 4/312 (1.3%) | 4 |
| Dyspnoea | 27/309 (8.7%) | 29 | 25/312 (8%) | 26 |
| Haemoptysis | 24/309 (7.8%) | 27 | 25/312 (8%) | 34 |
| Skin and subcutaneous tissue disorders | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 32/309 (10.4%) | 34 | 3/312 (1%) | 3 |
| Pruritus | 27/309 (8.7%) | 35 | 24/312 (7.7%) | 28 |
| Rash | 39/309 (12.6%) | 51 | 29/312 (9.3%) | 32 |
| Vascular disorders | ||||
| Hypertension | 121/309 (39.2%) | 144 | 44/312 (14.1%) | 49 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme LLC |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT03829332
Other Study ID Numbers:
- 7902-007
- MK-7902-007
- E7080-G000-314
- LEAP-007
- 194670
- 2018-003794-98
First Posted:
Feb 4, 2019
Last Update Posted:
Jun 2, 2022
Last Verified:
May 1, 2022