臨床研究等提出・公開システム

A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) in Participants With Treatment-naive, Metastatic Nonsmall Cell Lung Cancer (NSCLC) Whose Tumors Have a Tumor Proportion Score (TPS) Greater Than or Equal to 1% (LEAP-007)

Pembrolizumab with or without lenvatinib in TPS >=1% NSCLC

623

In the overall participants, the mean age was 65.0 years; 72.9% were male and 27.1% were female; 61.2% were White, and 33.2% were Asian.

309 participants and 314 participants were randomized to the pembrolizumab + lenvatinib group and the pembrolizumab + placebo group, respectively; of these, 309 participants in the pembrolizumab + lenvatinib group and 312 participants in the pembrolizumab + placebo group received the study treatment. As of 19-May-2021, 155 participants in the pembrolizumab + lenvatinib group and 139 participants in the pembrolizumab +placebo group discontinued from the study.

The proportions of participants with serious adverse events were 56.6% in the pembrolizumab + lenvatinib group and 34.0% in the pembrolizumab + placebo group. The most frequently reported serious adverse event was pneumonia (9.1% of participants in the pembrolizumab + lenvatinib group and 5.1% of participants in the pembrolizumab + placebo group) in both treatment groups. The proportions of participants with non-serious adverse events with an incidence of >5% in one or more treatment groups were 94.5% in the pembrolizumab + lenvatinib group and 86.2% in the pembrolizumab + placebo group. The most frequently reported non-serious adverse events were hypothyroidism (40.1%), hypertension (39.2%), diarrhoea (32.0%), proteinuria (32.0%), decreased appetite (24.6%), weight decreased (24.0%), and nausea (21.0%) in the pembrolizumab + lenvatinib group, and anaemia (20.2%) in the pembrolizumab + placebo group.

The median progression-free survival (PFS) was 6.6 months in the pembrolizumab + lenvatinib group and 4.2 months in the pembrolizumab + placebo group; the hazard ratio was 0.78 (95% CI: 0.64, 0.95; p=0.00624). The median overall survival (OS) was 14.1 months in the pembrolizumab + lenvatinib group and 16.4 months in the pembrolizumab + placebo group; the hazard ratio was 1.10 (95% CI: 0.87, 1.39; p=0.79744).

The overall response rate (ORR) was 40.5% in the pembrolizumab + lenvatinib group and 27.7% in the pembrolizumab + placebo group.

The combination of pembrolizumab and lenvatinib as first-line treatment for PD-L1-positive non-small cell lung cancer has not been shown to be more effective in extending OS than pembrolizumab alone.

Dec. 10, 2020

https://clinicaltrials.gov/ct2/bye/rQoPWwoRrXS9-i-wudNgpQDxudhWudNzlXNiZip9Ei7ym67VZRFRFR4tFgFnA6h9Ei4L3BUgWwNG0it.

Yes

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

https://clinicaltrials.gov/ProvidedDocs/32/NCT03829332/Prot_SAP_000.pdf

Tanaka Yoshiyuki

MSD K.K.

KITANOMARU SQUARE,1-13-12,Kudan-kita,Chiyoda-ku,Tokyo 102-8667,Japan

JPCT@msd.com

MSDJRCT inquiry mailbox

MSD K.K.

KITANOMARU SQUARE,1-13-12,Kudan-kita,Chiyoda-ku,Tokyo 102-8667,Japan

+81-3-6272-1957

JPCT@msd.com

completed

April. 08, 2019

Interventional

randomized,parallel assignment,Multicenter clinical study,double blind

treatment purpose

3

1) Has a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)

2) Has Stage IV NSCLC (American Joint Committee on Cancer [AJCC])
Has measurable disease based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

3) 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

4) Has a life expectancy of >=3 months

5) 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

6) 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)

7) 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 2) 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

8) 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

9) Has adequate organ function

Has known untreated central nervous system metastases and/or carcinomatous meningitis
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 radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
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 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 non-gastrointestinal fistula

Both

Non-small Cell Lung Cancer

Investigational material(s)
Generic name etc:
Pembrolizumab+Lenvatinib
INN of investigational material:
Pembrolizumab, Lenvatinib
Therapeutic category code:
42- Antineoplastic agents
Dosage and Administration for Investigational material:
Pembrolizumab 200mg IV Q3W + Lenvatinib 20mg PO QD
(35 cycles or until reaching a discontinuation criterion)
Lenvatinib 20mg PO QD
(36 cycles - until reaching a discontinuation criterion)

Control material(s)
Generic name etc:
Pembrolizumab+Placebo
INN of investigational material:
Pembrolizumab
Therapeutic category code:
429- Other antitumor agents
Dosage and Administration for Investigational material:
Pembrolizumab 200mg IV Q3W + Placebo PO QD
(35 cycles or until reaching a discontinuation criterion)
Placebo PO QD
(36 cycles - until reaching a discontinuation criterion)

PFS perRECIST 1.1 based onBICR
OS

ORR perRECIST 1.1 based onBICR
Safety and tolerability
Change from baseline inGlobal health status/QoL, cough, chest pain, dyspnea andphysical functioningscores
Time to True Deterioration (TTD)in global health status/QoL, cough, chest pain, dyspnea, and physical functioning
TTD in the composite endpoint of cough, chest pain, or dyspneaitems

Feb. 22, 2019