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)

Completed · Phase 3

Conditions studied: Metastatic Non-Small Cell Lung Cancer

In brief

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).

Key facts

Study ID: NCT03976375
Run by: Merck Sharp & Dohme LLC
People needed: 422
Starts: 2019-06-26
Expected to finish: 2024-08-22
Last updated by the study team: 2025-08-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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.

You may not qualify if…

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.

Where it is running

Cancer Specialists of North Florida - Fleming Island ( Site 1675) — Fleming Island, Florida, United States
Mid-Florida Cancer Centers ( Site 1611) — Orange City, Florida, United States
University of Kentucky School of Medicine & Hospitals ( Site 1621) — Lexington, Kentucky, United States
Hematology Oncology Clinic ( Site 1680) — Baton Rouge, Louisiana, United States
Harry & Jeanette Weinberg Cancer Institute ( Site 1626) — Baltimore, Maryland, United States
Medstar Good Samaritan Hospital ( Site 1625) — Baltimore, Maryland, United States
Massachusetts General Hospital ( Site 1622) — Boston, Massachusetts, United States
MGH - North Shore Cancer Center ( Site 1668) — Danvers, Massachusetts, United States
The Mass General Cancer Center at Newton-Wellesley ( Site 1692) — Newton, Massachusetts, United States
University of Massachusetts Medical School ( Site 1693) — Worcester, Massachusetts, United States
Billings Clinic ( Site 1631) — Billings, Montana, United States
Bozeman Health Deaconness Cancer Center ( Site 1632) — Bozeman, Montana, United States
Memorial Sloan-Kettering Cancer Center At Basking Ridge ( Site 1664) — Basking Ridge, New Jersey, United States
Memorial Sloan-Kettering Cancer Center at Middletown ( Site 1665) — Middletown, New Jersey, United States
Memorial Sloan-Kettering Cancer Center at Montvale ( Site 1667) — Montvale, New Jersey, United States
Memorial Sloan-Kettering Cancer Center at Commack ( Site 1662) — Commack, New York, United States
Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 1666) — Harrison, New York, United States
Memorial Sloan-Kettering Cancer Center ( Site 1661) — New York, New York, United States
New York Cancer and Blood Specialists ( Site 1696) — Port Jefferson Station, New York, United States
University of Rochester ( Site 1638) — Rochester, New York, United States
Memorial Sloan Kettering Cancer Center - Nassau ( Site 1670) — Uniondale, New York, United States
TriHealth Cancer Institute ( Site 1672) — Cincinnati, Ohio, United States
MetroHealth Medical Center ( Site 1694) — Cleveland, Ohio, United States
Kaiser Permanente Center for Health Research-Kaiser Permanente Medical Center ( Site 1644) — Portland, Oregon, United States
Comprehensive Blood & Cancer Center [Bakersfield, CA] ( Site 1604) — Bakersfield, California, United States

Full record on ClinicalTrials.gov

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