Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03976375




Registration number
NCT03976375
Ethics application status
Date submitted
3/06/2019
Date registered
6/06/2019
Date last updated
18/11/2024

Titles & IDs
Public title
Efficacy and Safety of Pembrolizumab (MK-3475) With Lenvatinib (E7080/MK-7902) vs. Docetaxel in Participants With Metastatic Non-Small Cell Lung Cancer (NSCLC) and Progressive Disease (PD) After Platinum Doublet Chemotherapy and Immunotherapy (MK-7902-008/E7080-G000-316/LEAP-008)
Scientific title
A Phase 3, Multicenter, Randomized, Open-label Trial to Compare the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Lenvatinib (E7080/MK-7902) Versus Docetaxel in Previously Treated Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) and Progressive Disease (PD) After Platinum Doublet Chemotherapy and Immunotherapy (LEAP-008)
Secondary ID [1] 0 0
MK-7902-008
Secondary ID [2] 0 0
7902-008
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Drugs - Lenvatinib
Treatment: Drugs - Docetaxel

Experimental: Pembrolizumab+Lenvatinib - Participants receive pembrolizumab at 200 mg, every 3 weeks (Q3W) via intravenous (IV) infusion on Day 1 of each 21-day cycle, in combination with lenvatinib at 20 mg, once daily (QD) via oral capsule. Pembrolizumab will be administered for up to 35 treatment cycles (\~2 years). Lenvantinib will be administered until progressive disease or unacceptable toxicity.

Active comparator: Docetaxel - Participants receive docetaxel at 75 mg/m\^2, Q3W via IV infusion over 1-hour infusion on Day 1 of each 21-day cycle. Docetaxel will be administered until progressive disease or unacceptable toxicity.

Experimental: Lenvatinib Monotherapy - Participants receive lenvatinib at 24 mg, QD via oral capsule. Lenvantinib will be administered until progressive disease or unacceptable toxicity.


Treatment: Other: Pembrolizumab
IV infusion of pembrolizumab at 200 mg

Treatment: Drugs: Lenvatinib
Oral capsules (unit strength: 4 and 10 mg) at 20 mg or 24 mg total daily dose.

Treatment: Drugs: Docetaxel
IV infusion of docetaxel at 75 mg/m\^2.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to ~47 months
Primary outcome [2] 0 0
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [2] 0 0
Up to ~47 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Docetaxel
Timepoint [1] 0 0
Up to ~47 months
Secondary outcome [2] 0 0
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Lenvatinib Monotherapy
Timepoint [2] 0 0
Up to ~47 months
Secondary outcome [3] 0 0
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [3] 0 0
Up to ~47 months
Secondary outcome [4] 0 0
Number of Participants Experiencing an Adverse Event (AE)
Timepoint [4] 0 0
Up to ~47 months
Secondary outcome [5] 0 0
Number of Participants Discontinuing Study Treatment Due to an AE
Timepoint [5] 0 0
Up to ~47 months
Secondary outcome [6] 0 0
Change From Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score
Timepoint [6] 0 0
Baseline and Week 12
Secondary outcome [7] 0 0
Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 31) Scale Score
Timepoint [7] 0 0
Baseline and Week 12
Secondary outcome [8] 0 0
Change From Baseline in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score
Timepoint [8] 0 0
Baseline and Week 12
Secondary outcome [9] 0 0
Change From Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
Timepoint [9] 0 0
Baseline and Week 12
Secondary outcome [10] 0 0
Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score
Timepoint [10] 0 0
Baseline and Week 12
Secondary outcome [11] 0 0
Time to True Deterioration (TTD) in EORTC QLQ-C30 Combined Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score
Timepoint [11] 0 0
Up to 24 months
Secondary outcome [12] 0 0
Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score
Timepoint [12] 0 0
Up to ~24 months
Secondary outcome [13] 0 0
Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score
Timepoint [13] 0 0
Up to ~24 months
Secondary outcome [14] 0 0
Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
Timepoint [14] 0 0
Up to ~24 months
Secondary outcome [15] 0 0
Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score
Timepoint [15] 0 0
Up to ~24 months

Eligibility
Key inclusion criteria
* Has a histologically or cytologically confirmed diagnosis of metastatic squamous or nonsquamous Non-Small Cell Lung Cancer (NSCLC) -Stage IV: M1a, M1b, M1c.
* Has progressive disease (PD) on treatment with one prior anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies.

* Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall course of treatment
* Has PD during/after platinum doublet chemotherapy for metastatic disease.
* Has confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy (documentation of absence of tumor-activating EGFR mutations [eg, DEL19 or L858R], and absence of ALK and ROS1 gene rearrangements OR presence of a K-ras mutation).
* Has submitted pre-study imaging that confirmed evidence of PD following initiation of an anti-PD-1/PD-L1 inhibitor.
* Has at least 1 measurable lesion by computerized tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, as determined by the local site assessment.
* Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample (defined as: from initial diagnosis of NSCLC and prior to receiving immunotherapy [antiPD-1/PD-L1], from the primary lesion or a metastatic lesion).
* Has provided prior to allocation tissue from a newly obtained formalin-fixed sample from a new biopsy (defined as: after completion of immunotherapy [anti-PD-1/PD-L1] and before receiving a randomization number), of a tumor lesion not previously irradiated.
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study intervention but before randomization.
* Has a life expectancy of at least 3 months.
* Male participants receiving pembrolizumab ± lenvatinib or lenvatinib must agree to refrain from donating sperm, and either 1) be abstinent from heterosexual intercourse; or 2) follow contraceptive guidance during the treatment period or 7 days after the last dose of lenvatinib. Male participants receiving docetaxel agree to adhere to the same conditions during the treatment period and for =90 days after the last dose of study treatment.
* Female participants must not be pregnant, not be breastfeeding, and not be a woman of child-bearing potential (WOCBP). If a WOCBP, agrees to not donate eggs and either use contraception, or be abstinent from heterosexual intercourse during the treatment period and for =120 days after the last dose of pembrolizumab or 30 days after the last dose of lenvatinib, whichever occurs last. If a WOCBP receiving docetaxel, agrees to adhere to the same conditions during the treatment period and for =30 days after the last dose of study treatment.
* 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.
* If participant received major surgery or radiation therapy of >30 Gy, they have recovered from the toxicity and/or complications from the intervention.
* Has adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has received docetaxel as monotherapy or in combination with other therapies.
* Has received lenvatinib as monotherapy or in combination with an anti-PD-1/PD-L1 mAb.
* Has received: 1) radiotherapy within 2 weeks before the first dose of study treatment; or 2) lung radiation therapy >30 Gy within 6 months before the first dose of study treatment.
* Has received a live vaccine within 30 days before the first dose of study treatment.
* Has clinically significant hemoptysis or tumor bleeding within 2 weeks before the first dose of study treatment.
* Has radiographic evidence of intratumoral cavitation, encasement, or invasion of a major blood vessel.
* Has clinically significant cardiovascular impairment within 12 months of the first dose of study treatment.
* Has a history of a gastrointestinal condition or procedure that may affect oral absorption of study treatment.
* Has a pre-existing =Grade 3 gastrointestinal or non-gastrointestinal fistula.
* Is currently participating in a clinical trial and receiving study therapy or participated in a study of an investigational agent within 4 weeks of the first dose of study treatment.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment.
* Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of disease recurrence for 3 years since initiation of that therapy.
* Has known active central nervous system metastases and/or carcinomatous meningitis.
* Has severe hypersensitivity to pembrolizumab and/or any of its excipients.
* Has a sensitivity to any of the excipients contained in lenvatinib and/or docetaxel.
* Has an active autoimmune disease that has required systemic treatment in the past 2 years.
* Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
* Has an active infection requiring systemic therapy.
* Has a known history of human immunodeficiency virus (HIV) infection.
* Has a known history of hepatitis B reactive or known active hepatitis C virus infection.
* Has active tuberculosis.
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through at least 120 days after the last dose of pembrolizumab or lenvatinib, or 90 days (male participants) or 30 days (for female participants) after the last dose of docetaxel.
* Has had an allogeneic tissue/solid organ transplant.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/08/2024
Sample size
Target
Accrual to date
Final
422
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital ( Site 0004) - Blacktown
Recruitment hospital [2] 0 0
Port Macquarie Base Hospital ( Site 0003) - Port Macquarie
Recruitment hospital [3] 0 0
Westmead Hospital ( Site 0005) - Westmead
Recruitment hospital [4] 0 0
Southern Medical Day Care Centre ( Site 0001) - Wollongong
Recruitment hospital [5] 0 0
Princess Alexandra Hospital - Division of Cancer Services ( Site 0002) - Woolloongabba
Recruitment hospital [6] 0 0
Calvary Central Districts Hospital ( Site 0007) - Elizabeth Vale
Recruitment hospital [7] 0 0
Bendigo Cancer Centre ( Site 0008) - Bendigo
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
2500 - Wollongong
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [7] 0 0
3552 - Bendigo
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Montana
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Caba
Country [17] 0 0
Argentina
State/province [17] 0 0
Santa Fe
Country [18] 0 0
Canada
State/province [18] 0 0
Manitoba
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
Colombia
State/province [21] 0 0
Antioquia
Country [22] 0 0
Colombia
State/province [22] 0 0
Atlantico
Country [23] 0 0
Colombia
State/province [23] 0 0
Cesar
Country [24] 0 0
Colombia
State/province [24] 0 0
Cordoba
Country [25] 0 0
Colombia
State/province [25] 0 0
Distrito Capital De Bogota
Country [26] 0 0
Colombia
State/province [26] 0 0
Valle Del Cauca
Country [27] 0 0
France
State/province [27] 0 0
Calvados
Country [28] 0 0
France
State/province [28] 0 0
Hauts-de-Seine
Country [29] 0 0
France
State/province [29] 0 0
Maine-et-Loire
Country [30] 0 0
France
State/province [30] 0 0
Pas-de-Calais
Country [31] 0 0
France
State/province [31] 0 0
Provence-Alpes-Cote-d Azur
Country [32] 0 0
France
State/province [32] 0 0
Sarthe
Country [33] 0 0
France
State/province [33] 0 0
Paris
Country [34] 0 0
Germany
State/province [34] 0 0
Baden-Wurttemberg
Country [35] 0 0
Germany
State/province [35] 0 0
Nordrhein-Westfalen
Country [36] 0 0
Germany
State/province [36] 0 0
Thuringen
Country [37] 0 0
Germany
State/province [37] 0 0
Berlin
Country [38] 0 0
Greece
State/province [38] 0 0
Attiki
Country [39] 0 0
Greece
State/province [39] 0 0
Ioannina
Country [40] 0 0
Greece
State/province [40] 0 0
Thessaloniki
Country [41] 0 0
Hungary
State/province [41] 0 0
Borsod-Abauj-Zemplen
Country [42] 0 0
Hungary
State/province [42] 0 0
Fejer
Country [43] 0 0
Hungary
State/province [43] 0 0
Gyor-Moson-Sopron
Country [44] 0 0
Hungary
State/province [44] 0 0
Jasz-Nagykun-Szolnok
Country [45] 0 0
Hungary
State/province [45] 0 0
Pest
Country [46] 0 0
Hungary
State/province [46] 0 0
Veszprem
Country [47] 0 0
Hungary
State/province [47] 0 0
Budapest
Country [48] 0 0
Israel
State/province [48] 0 0
Beer Sheva
Country [49] 0 0
Israel
State/province [49] 0 0
Haifa
Country [50] 0 0
Israel
State/province [50] 0 0
Jerusalem
Country [51] 0 0
Israel
State/province [51] 0 0
Kfar-Saba
Country [52] 0 0
Israel
State/province [52] 0 0
Petah Tikva
Country [53] 0 0
Israel
State/province [53] 0 0
Ramat Gan
Country [54] 0 0
Israel
State/province [54] 0 0
Tel Aviv
Country [55] 0 0
Italy
State/province [55] 0 0
Monza E Brianza
Country [56] 0 0
Italy
State/province [56] 0 0
Roma
Country [57] 0 0
Italy
State/province [57] 0 0
Sicilia
Country [58] 0 0
Italy
State/province [58] 0 0
Torino
Country [59] 0 0
Italy
State/province [59] 0 0
Avellino
Country [60] 0 0
Italy
State/province [60] 0 0
Bari
Country [61] 0 0
Italy
State/province [61] 0 0
Catania
Country [62] 0 0
Italy
State/province [62] 0 0
Milano
Country [63] 0 0
Italy
State/province [63] 0 0
Pavia
Country [64] 0 0
Italy
State/province [64] 0 0
Perugia
Country [65] 0 0
Japan
State/province [65] 0 0
Kanagawa
Country [66] 0 0
Japan
State/province [66] 0 0
Miyagi
Country [67] 0 0
Japan
State/province [67] 0 0
Osaka
Country [68] 0 0
Japan
State/province [68] 0 0
Chiba
Country [69] 0 0
Japan
State/province [69] 0 0
Niigata
Country [70] 0 0
Japan
State/province [70] 0 0
Tokyo
Country [71] 0 0
Korea, Republic of
State/province [71] 0 0
Chungbuk
Country [72] 0 0
Korea, Republic of
State/province [72] 0 0
Kyonggi-do
Country [73] 0 0
Korea, Republic of
State/province [73] 0 0
Seoul
Country [74] 0 0
Portugal
State/province [74] 0 0
Lisboa
Country [75] 0 0
Portugal
State/province [75] 0 0
Porto
Country [76] 0 0
Puerto Rico
State/province [76] 0 0
Manati
Country [77] 0 0
Puerto Rico
State/province [77] 0 0
Ponce
Country [78] 0 0
Puerto Rico
State/province [78] 0 0
San Juan
Country [79] 0 0
Russian Federation
State/province [79] 0 0
Baskortostan, Respublika
Country [80] 0 0
Russian Federation
State/province [80] 0 0
Krasnoyarskiy Kray
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Moskva
Country [82] 0 0
Russian Federation
State/province [82] 0 0
Omskaya Oblast
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Sankt-Peterburg
Country [84] 0 0
Spain
State/province [84] 0 0
Asturias
Country [85] 0 0
Spain
State/province [85] 0 0
Barcelona
Country [86] 0 0
Spain
State/province [86] 0 0
Cantabria
Country [87] 0 0
Spain
State/province [87] 0 0
Las Palmas
Country [88] 0 0
Spain
State/province [88] 0 0
Madrid
Country [89] 0 0
Spain
State/province [89] 0 0
Valenciana, Comunitat
Country [90] 0 0
Spain
State/province [90] 0 0
Jaen
Country [91] 0 0
United Kingdom
State/province [91] 0 0
East Riding Of Yorkshire
Country [92] 0 0
United Kingdom
State/province [92] 0 0
England
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Leicestershire
Country [94] 0 0
United Kingdom
State/province [94] 0 0
London, City Of
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Scotland
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Warwickshire
Country [97] 0 0
United Kingdom
State/province [97] 0 0
Birmingham
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Leeds

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eisai Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the efficacy and safety of pembrolizumab (MK-3475) with lenvatinib (E7080/MK-7902) vs. docetaxel in participants with metastatic non-small cell lung cancer (NSCLC) and progressive disease (PD) after platinum doublet chemotherapy and treatment with one prior anti-PD-1/PD-L1 monoclonal antibody (mAb). The primary hypotheses of this study are that pembrolizumab + lenvatinib (compared with docetaxel) prolongs: 1) overall survival (OS); and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review (BICR).
Trial website
https://clinicaltrials.gov/study/NCT03976375
Trial related presentations / publications
Xing P, Wang M, Zhao J, Zhong W, Chi Y, Xu Z, Li J. Study protocol: A single-arm, multicenter, phase II trial of camrelizumab plus apatinib for advanced nonsquamous NSCLC previously treated with first-line immunotherapy. Thorac Cancer. 2021 Oct;12(20):2825-2828. doi: 10.1111/1759-7714.14113. Epub 2021 Aug 18.
Taylor MH, Schmidt EV, Dutcus C, Pinheiro EM, Funahashi Y, Lubiniecki G, Rasco D. The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Future Oncol. 2021 Feb;17(6):637-648. doi: 10.2217/fon-2020-0937. Epub 2020 Dec 10.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03976375