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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03976375




Registration number
NCT03976375
Ethics application status
Date submitted
3/06/2019
Date registered
6/06/2019
Date last updated
8/03/2024

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
Other interventions - 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.


Other interventions: 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
Other interventions
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 ~48 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 ~36 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 ~18 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 ~36 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 ~48 months
Secondary outcome [4] 0 0
Number of Participants Experiencing an Adverse Event (AE)
Timepoint [4] 0 0
Up to ~79 months
Secondary outcome [5] 0 0
Number of Participants Discontinuing Study Treatment Due to an AE
Timepoint [5] 0 0
Up to ~79 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 ~48 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 ~48 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 ~48 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 ~48 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 ~48 months

Eligibility
Key inclusion criteria
- Has a histologically or cytologically confirmed diagnosis of metastatic squamous or
nonsquamous NSCLC (Stage IV: M1a, M1b, M1c).

- Has PD on treatment with one prior anti-PD-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 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
Active, not recruiting
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
18/09/2024
Actual
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
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Oregon
Country [12] 0 0
United States of America
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Pennsylvania
Country [13] 0 0
United States of America
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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
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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
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Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
Colombia
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Antioquia
Country [22] 0 0
Colombia
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Atlantico
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Colombia
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Cesar
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Colombia
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Cordoba
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Colombia
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Distrito Capital De Bogota
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Colombia
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Valle Del Cauca
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France
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Calvados
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France
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Hauts-de-Seine
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France
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Maine-et-Loire
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France
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Pas-de-Calais
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France
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Provence-Alpes-Cote-d Azur
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France
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Sarthe
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France
State/province [33] 0 0
Paris
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Germany
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Baden-Wurttemberg
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Germany
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Nordrhein-Westfalen
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Germany
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Thuringen
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Germany
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Berlin
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Greece
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Attiki
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Greece
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Ioannina
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Greece
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Thessaloniki
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Hungary
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Borsod-Abauj-Zemplen
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Hungary
State/province [42] 0 0
Fejer
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Hungary
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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
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Hungary
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Veszprem
Country [47] 0 0
Hungary
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Budapest
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Israel
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Beer Sheva
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Kfar-Saba
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Israel
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Petah Tikva
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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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
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Italy
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Milano
Country [63] 0 0
Italy
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Pavia
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Italy
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Perugia
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Japan
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Kanagawa
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Japan
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Miyagi
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Japan
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Osaka
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Japan
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Chiba
Country [69] 0 0
Japan
State/province [69] 0 0
Niigata
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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
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Portugal
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Porto
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Puerto Rico
State/province [76] 0 0
Manati
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Puerto Rico
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Ponce
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Puerto Rico
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San Juan
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Russian Federation
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Baskortostan, Respublika
Country [80] 0 0
Russian Federation
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Krasnoyarskiy Kray
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Moskva
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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
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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
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Jaen
Country [91] 0 0
United Kingdom
State/province [91] 0 0
East Riding Of Yorkshire
Country [92] 0 0
United Kingdom
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England
Country [93] 0 0
United Kingdom
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Leicestershire
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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/ct2/show/NCT03976375
Trial related presentations / publications
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/ct2/show/NCT03976375