Non-squamous Non-small-cell Lung CancerPhase 2NCT05258279
Lenvatinib in Combination With Carboplatin Pemetrexed and Pembrolizumab for NSCLC With EGFR Mutations
A Phase 2 study testing Pembrolizumab, Lenvatinib and Carboplatin in people with Non-squamous Non-small-cell Lung Cancer and EGFR Activating Mutation, run by Juntendo University at 10 sites in Japan.
Trial summary
The purpose of this study is to assess the safety and efficacy of pemetrexed + carboplatin + pembrolizumab (MK-3475) with lenvatinib (MK-7902/E7080) in patients with advanced nonsquamous non-small cell lung cancer harboring EGFR mutations. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Non-squamous Non-small-cell Lung Cancer, EGFR Activating Mutation
- What is being tested?
- Pembrolizumab, Lenvatinib and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 10 sitesJapan
- Study dates
- 1 Jul 2022to 31 Oct 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a histologically or cytologically confirmed diagnosis of incurable Stage IIIB, IIIC, IVA, IVB (American Joint Committee on Cancer [AJCC], version 8) non-squamous NSCLC. Postoperative recurrence is acceptable if the disease is not curable.
- Have documentation of tumor activating EGFR mutation, specifically either exon 19 deletion or exon 21 L858R.
- Have investigator determined radiographic disease progression per RECIST 1.1 after treatment with EGFR-TKI therapy:
- Participants previously treated with 1st or 2nd generation EGFR TKI (eg, erlotinib/afatinib/gefitinib) are required to have confirmed documented absence of EGFR T790M mutation.
- Participants with confirmed acquired T790M mutation after 1st or 2nd generation EGFR-TKI (eg, erlotinib/afatinib/gefitinib) are required to have osimertinib TKI treatment failure prior to enrollment.
- Participants previously failed osimertinib TKI treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status.
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- Participants treated with a combination of EGFR TKIs and antibodies targeting the VEGF pathway will also be eligible.
- Have measurable disease per RECIST 1.1.
- Be male or female ≥ 20 years of age inclusive, at the time of signing the informed consent form (ICF).
- Have a life expectancy of at least 3 months.
- Have an ECOG performance status of 0 or 1 within 7 days prior to the first dose of study intervention but before registration.
- A male participant must agree to use a contraception during the treatment period.
- A female participant is eligible to participate if she is not pregnant, not breastfeeding
- The participant provides written informed consent for the study.
- Have adequate organ function.
- Have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤ 150/90 mmHg and no change in antihypertensive medications within 1 week prior to registration.
Who cannot join
- Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable, and have not required steroids for at least 14 days prior to the first dose of study intervention.
- Has history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
- Radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered because for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy (in the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta).
- Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease of that disease recurrence for at least 3 year since initiation of that therapy.
- Has an autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
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- Has had an allogeneic tissue/solid organ transplant.
- Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive or HBV-DNA detected) or known active Hepatitis C virus (HCV antibody reactive).
- Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral drug absorption.
- Has active hemoptysis (at least 0.5 tsp of bright red blood) within 2 weeks prior to the first dose of study intervention.
- Has significant cardiovascular impairment within 12 months prior to the first dose of study intervention, including history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability.
- Has a known history of active tuberculosis.
- Has an active infection requiring systemic therapy.
- Has had major surgery within 3 weeks prior to first dose of study interventions.
- Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
- Has known psychiatric or substance abuse disorders that would interfere with the participant's cooperation to meet with the requirements of the study.
- Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has s known sensitivity to any component of lenvatinib or pembrolizumab, or as applicable, carboplatin, or pemetrexed.
- A women of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has preexisting ≥ Grade 3 gastrointestinal or non-gastrointestinal fistula. Prior/Concomitant Therapy
- Has received prior systemic cytotoxic chemotherapy for their metastatic NSCLC. Note: Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic NSCLC.
- Has received prior treatment with pembrolizumab or any other anti-PD-1, anti-PD-L1, anti-PD-L2 agent, with lenvatinib or any other RTKi, or with an agent directed to another stimulatory or co-inhibitory T cell receptor (eg, CTLA-4, OX-40, CD137, GITR).
- Has received radiotherapy within 14 days prior to the first dose of study intervention or received lung radiation therapy of > 30 Gy within 6 months prior to the first dose of study intervention.
- Has received systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of study intervention.
- Has received a live vaccine within 30 days prior to the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, and Bacillus Calmette-Guerin (BCG). Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed.
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study intervention.
- Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been > 4 weeks after the last dose of the previous investigational agent.
- Participants with proteinuria > 1+ on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥ 1 g/24 hours will be ineligible.
- Has a prolongation of QTc interval (calculated using Fridericia's formula) of > 480 msec.
- Has left ventricular ejection fraction (LVFE) below 50% as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's ability to participate for the full duration of the study, or make it not in the best interest of the participant to participate, in the opinion of the treating investigator.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Japan10 sites
Juntendo University Hospital
Bunkyo-ku, Tokyo, 113-8431
Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
Bunkyo-ku, Tokyo, 113-8677
Chiba University Hospital
Chiba, Chiba, 26-8677
Saitama Medical University International Medical Center
Hidaka, Saitama, 350-1298
St. Marianna University Hospital
Kawasaki, Kanagawa, 216-8511
Shizuoka Cancer Center
Nagaizumi-cho, Shizuoka, 411-8777
Saitama Cancer Center
Shinden, Saitama, 362-0806
Juntendo Urayasu Hospital
Urayasu, Chiba, 279-0021
Kanagawa Cardiovascular and Respiratory Center
Yokohama, Kanagawa, 236-0051
Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515
About this study
Official title: A Phase II Study of Lenvatinib (E7080/MK-7902) in Combination With Carboplatin Pemetrexed and Pembrolizumab (MK-3475) for Patients With Pretreated Advanced Non-squamous Non-small Cell Lung Cancer Harboring EGFR Mutations
The purpose of this study is to assess the safety and efficacy of pemetrexed + carboplatin + pembrolizumab (MK-3475) with lenvatinib (MK-7902/E7080) in patients with advanced nonsquamous non-small cell lung cancer harboring EGFR mutations.
- Being tested
- Pembrolizumab, Lenvatinib, Carboplatin, Pemetrexed
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called MK-3475
IV infusion Q3W
LenvatinibDrug
Also called MK-7902, E7080
Oral capsule once daily
CarboplatinDrug
IV infusion Q3W
PemetrexedDrug
IV infusion Q3W
| Study group | Role | What they receive |
|---|---|---|
| Pemetrexed+Carboplatin+Pembrolizumab+Lenvatinib | Experimental | Participants receive carboplatin Area Under Curve 5 mg/mL/min (AUC5) via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for 4 cycles PLUS pemetrexed 500 mg/m^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS lenvatinib via oral capsule once daily for up to 2 years. Receives: Drug: Pembrolizumab; Drug: Lenvatinib; Drug: Carboplatin; Drug: Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) as Assessed by BICR according to RECIST 1.1
ORR is 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.
Measured: Up to approximately 18 months
Secondary outcomes (6)
Objective Response Rate (ORR) as Assessed by investigators according to RECIST 1.1.
ORR is 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.
Measured: Up to approximately 18 months
Progression-free Survival (PFS) as Assessed by investigators according to RECIST 1.1
PFS is 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 occurs first. Per RECIST 1.1.
Measured: Up to approximately 30 months
Overall Survival (OS)
OS is defined as the time from randomization to the time of death from any cause. OS will be presented.
Measured: Up to approximately 30 months
Duration of Response (DOR) as Assessed by investigators according to RECIST 1.1.
For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until PD or death from any cause, whichever occurs first. Per RECIST 1.1.
Measured: Up to approximately 30 months
Number of Participants with One or More Adverse Events
An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measured: Up to approximately 30 months
Disease Control Rate (DCR) as Assessed by investigators according to RECIST 1.1.
ORR is 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) or Stable Disease (SD) per RECIST 1.1.
Measured: Up to approximately 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2022
- Study start1 Jul 2022
- Primary completion31 Oct 2023
- Study completion31 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-squamous Non-small-cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Juntendo University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Ryo Ko, Juntendo University
- Investigators
- Ryo Ko, MD, PhD, Principal investigator, Department of Respiratory Medicine, Juntendo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05258279
- Sponsor's protocol ID
- NEJ052
- Status last verified
- Jul 2026
- First submitted
- 17 Feb 2022
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Lenvatinib (E7080/MK-7902) in Combination With Carboplatin Pemetrexed and Pembrolizumab (MK-3475) for Patients With Pretreated Advanced Non-squamous Non-small Cell Lung Cancer Harboring EGFR Mutations
- ClinicalTrials.gov ID
- NCT05258279
- Acronym / sponsor ID
- NEJ052
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Juntendo UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 31 Oct 2023 (actual)
- Study completion
- 31 Oct 2024 (actual)
- First posted
- 28 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety and efficacy of pemetrexed + carboplatin + pembrolizumab (MK-3475) with lenvatinib (MK-7902/E7080) in patients with advanced nonsquamous non-small cell lung cancer harboring EGFR mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pemetrexed+Carboplatin+Pembrolizumab+Lenvatinib | Experimental | Drug: Pembrolizumab, Drug: Lenvatinib, Drug: Carboplatin, Drug: PemetrexedParticipants receive carboplatin Area Under Curve 5 mg/mL/min (AUC5) via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for 4 cycles PLUS pemetrexed 500 mg/m^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS lenvatinib via oral capsule once daily for up to 2 years. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Have a histologically or cytologically confirmed diagnosis of incurable Stage IIIB, IIIC, IVA, IVB (American Joint Committee on Cancer [AJCC], version 8) non-squamous NSCLC. Postoperative recurrence is acceptable if the disease is not curable.
- Have documentation of tumor activating EGFR mutation, specifically either exon 19 deletion or exon 21 L858R.
- Have investigator determined radiographic disease progression per RECIST 1.1 after treatment with EGFR-TKI therapy:
- Have measurable disease per RECIST 1.1.
- Be male or female ≥ 20 years of age inclusive, at the time of signing the informed consent form (ICF).
Key exclusion criteria (31 listed)
- Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable, and have not required steroids for at least 14 days prior to the first dose of study intervention.
- Has history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
- Radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered because for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy (in the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta).
- Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease of that disease recurrence for at least 3 year since initiation of that therapy.
- Has an autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: MK-3475IV infusion Q3W | Drug | Pemetrexed+Carboplatin+Pembrolizumab+Lenvatinib |
| LenvatinibAlso: MK-7902, E7080Oral capsule once daily | Drug | Pemetrexed+Carboplatin+Pembrolizumab+Lenvatinib |
| CarboplatinIV infusion Q3W | Drug | Pemetrexed+Carboplatin+Pembrolizumab+Lenvatinib |
| PemetrexedIV infusion Q3W | Drug | Pemetrexed+Carboplatin+Pembrolizumab+Lenvatinib |
Primary outcome
Objective Response Rate (ORR) as Assessed by BICR according to RECIST 1.1
Time frame: Up to approximately 18 months
ORR is 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.
6 secondary outcomes
Objective Response Rate (ORR) as Assessed by investigators according to RECIST 1.1.
Time frame: Up to approximately 18 months
Progression-free Survival (PFS) as Assessed by investigators according to RECIST 1.1
Time frame: Up to approximately 30 months
Overall Survival (OS)
Time frame: Up to approximately 30 months
Duration of Response (DOR) as Assessed by investigators according to RECIST 1.1.
Time frame: Up to approximately 30 months
Number of Participants with One or More Adverse Events
Time frame: Up to approximately 30 months
Disease Control Rate (DCR) as Assessed by investigators according to RECIST 1.1.
Time frame: Up to approximately 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ryo Ko, MD, PhD principal investigator
Department of Respiratory Medicine, Juntendo University
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Lenvatinib and Carboplatin in people with Non-squamous Non-small-cell Lung Cancer and EGFR Activating Mutation, run by Juntendo University at 10 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) as Assessed by BICR according to RECIST 1.1 (time frame: Up to approximately 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2026; AzTrials last refreshed its copy on 8 Nov 2026.