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Non-small Cell Lung Cancer Stage IBPhase 2NCT04040361

Neoadjuvant Therapy of Pembrolizumab + Ramucirumab for PD-L1 Positive Stage IB-IIIA Lung Cancer (EAST ENERGY)

A Phase 2 study testing Pembrolizumab, Ramucirumab and Surgery in people with Non-small Cell Lung Cancer Stage IB and Non-small Cell Lung Cancer Stage II, run by National Cancer Center Hospital East at 2 sites in Japan.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The efficacy and safety of the neoadjuvant therapy of pembrolizumab+ ramucirumab Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
Pembrolizumab, Ramucirumab and Surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
2 sitesJapan
Study dates
30 Nov 2019to 31 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Male/female participants who are at least 20 years of age on the day of signing informed consent
  • Previously untreated and histologically proven NSCLC harboring PD-L1 expression (≥1% in a biopsy specimen), as measured by immunohistochemistry (22C3).
  • Resectable clinical stage IB-IIIA NSCLC carefully evaluated by experienced thoracic surgeons. (If N2 disease is suspected, the histological or cytological confirmation is mandatory) (UICC version 8)
  • Pulmonary resection more than lobectomy and lymph node dissection is considered to be possible for complete resection of the tumor.Be able to undergo protocol therapy, including necessary surgery.
  • Has adequate pulmonary function for pulmonary resection. Predicted postoperative FEV1.0 is 800 mL or more. ｛(predicted postoperative FEV1.0) = (preoperative FEV1.0) x (18-number of resected segment) / 18｝
  • ECOG performance status of 0 to 1.
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  • Has measurable disease as defined by RECIST 1.1 as determined by investigator.
  • Has adequate organ function as defined in the following criteria. Clinical test data must meet the following criteria within 14 days of the registration. The registration day is the standard, including the same day of the week two weeks prior.
  • a Neutrophil count: ≥ 1500/mm3 b Hemoglobin (Hb) ≥ 9.0 g/dL c Platelet count: ≥ 10.0 × 104/mm3 d AST (SGOT) ≤ 100 IU/L e ALT (SGPT): ≤ 100 IU/L f Total bilirubin: ≤ 1.5 mg/dL (Total bilirubin: ≤ 3.0 mg/dL for patient with Gilbert's syndrome) g Creatinine: CRE ≤ 1.5 mg/dL, or creatinine clearance of 40 mL/minute or higher [Even when the value is less than 40 mL/min in the Cockcroft-Gault equation, if the measured value from a 24-hour urine collection is 40 mL/min or higher, the patient qualifies.] Cockcroft-Gault equation: Male: Ccr=｛(140-age) × body weight (kg)｝/｛72 × serum CRE value (mg/dL）｝Female: Ccr=0.85 × ｛(140-age) × body weight (kg)｝/｛72 × serum CRE value (mg/dL) h SpO(2) ≥ 92% (room air) i International normalized ratio (INR) ≤ 1.5 j PTT(aPTT) ≤ 1.5 × ULN k Urinary protein ≤1+ (if it is ≥2+, store the urine for 24 hours, and if the urinary protein is <1,000 mg, the patient is qualified).
  • Female who are likely to become pregnant are negative with pregnancy tests (urine or serum) within 7 days prior to enrollment. They agree to conduct proper contraception (total abstinence, intrauterine contraceptive device, hormone release system, or contraceptive implant and oral contraceptive) for both men and women during the trial and from the final investigational dosing up to 120 days
  • The participant is willing and able to provide written informed consent/assent for the trial.

Who cannot join

  • Has one of the following tumor locations/types:
  • NSCLC involving the superior sulcus
  • Large cell neuro-endocrine cancer (LCNEC)
  • Sarcomatoid tumor
  • Synchronous lung cancer (within 5 years), current non-pure GGN on TSCT, or pure GGN with 15mm or more on TSCT
  • Has an active infection requiring systemic therapy.
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  • Has an active autoimmune disease that has required systemic treatment in 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) is not considered a form of systemic treatment and is allowed.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (dose exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug.
  • Has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Hypersensitivity or allergy to pembrolizumab, ramucirumab, or any of their excipients.
  • Has a known history of, or any evidence of active, interstitial lung disease.
  • Has a hypertension that is difficult to control (systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with several hypotensive agents.
  • Has an acute coronary syndrome (including myocardial infarction and unstable angina), and with a history of coronary angioplasty or stent placement performed within 6 months before enrollment
  • Has a history of New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months
  • Has a severe (hospitalization required) complications (intestinal palsy, intestinal obstruction, pulmonary fibrosis, diabetes difficult to control, heart failure, myocardial infarction, unstable angina, renal failure, liver failure, liver cirrhosis, mental disease, cerebrovascular disease etc).
  • Has a known history of human immunodeficiency virus (HIV) infection. No HIV resting is required unless mandated by local health authority.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Positivefor HBs antigens, HBs antibodies, and HBc antibodies. However, if positive for HBs and/or HBc antibodies, the patient can be registered as long as they are negative for HBV-DNA.
  • Positive for HCV antibody. However, if positive for HCV antibody, the patient can be registered as long as they are negative for HCV-RNA.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has a known additional malignancy that is progressing or requires active treatment within the past (5 years) or received anti-cancer drug including hormone therapy.
  • Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, bladder carcinoma, or carcinoma in situ (eg, in situ cervical cancer, breast carcinoma, CIS and AIS of the lung) that have undergone potentially curative therapy are not excluded.
  • Has received a live vaccine within 30 days prior to the first dose of trial drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening or screening visit through 120 days after the last dose of trial treatment.
  • Has history of hemoptysis (more than 1/2 cups in teaspoon) in 2 months before registration, or invasion of major vessels by cancer or major vessel narrowing is recognized on the image.
  • Image shows cavity formation in the tumor.
  • Is considered highly likely to have complications related to bleeding.
  • Obvious tumor invasion to the chest great vessel, cavity formation of the lung lesion, or the existence of obvious thrombus on the image are recognized, etc.
  • Has past history of gastrointestinal perforation, peptic ulcer, diverticulosis or fistula within 6 months.
  • ※ As for peptic ulcer, registration is permitted when disease condition is controlled by appropriate treatment.
  • Has a history of pulmonary embolism / deep vein thrombosis, or other thromboembolism within 3 months before registration.
  • Received major surgery within 28 days before registration, or received procedures for placement of subcutaneous venous access devices within seven days before registration.
  • Severe wounds, ulcers or fractures within 28 days before registration.
  • Has undergone long-term treatment using aspirin, nonsteroidal anti-inflammatory drugs (such as ibuprofen, naproxen), dipyridamole, clopidogrel or similar drugs. However, use of aspirin up to 325 mg / day once a day is acceptable.
  • Patients who are receiving anticoagulant therapy and whose dose of oral anticoagulant or low molecular weight heparin is not stable. In case of taking warfarin, registration is permitted if there is no active bleeding or no risk of bleeding.
  • 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 of registration.
  • Note: Participants who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
  • Has no intention to comply with the study protocol or it is impossible to comply.
  • Investigator or clinical trial doctor judged unsuitable as subject of this trial.

Trial locations and contacts

2 sites in 1 country.

Japan2 sites

  • National Cancer Center Hospital East

    Kashiwa, Chiba, 277-8577

  • Tokyo Medical University Hospita

    Shinjuku-Ku, Tokyo

Other trials in Japan

About this study

Official title: Efficacy and Safety of Neoadjuvant Therapy of Pembrolizumab Combined With Ramucirumab for PD-L1 Positive Stage IB-IIIA Lung Cancer: An Open-label Single-arm Phase II Study

The efficacy and safety of the neoadjuvant therapy of pembrolizumab+ ramucirumab

Read the detailed description

To demonstrate the antitumor activity and safety of neoadjuvant pembrolizumab plus ramucirumab followed by surgery in patients with PD-L1 positive stage IB-IIIA non-small cell lung cancer

Being tested
Pembrolizumab, Ramucirumab, Surgery
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called MK3475

    Pembrolizumab will be administered as a dose of 200mg as a 30-minutes IV infusion, Q3W

  • RamucirumabDrug

    Also called LY3009806

    Ramucirumab will be administered as a dose of 10mg/kg as a 60-minutes IV infusion, Q3W

  • SurgeryProcedure or surgery

    Surgery to be performed is lobectomy or more extensive lung resection and lymph node dissection

Study groups in NCT04040361
Study groupRoleWhat they receive
Pembrolizumab+Ramucirumab+SurgeryExperimentalPembrolizumab and Ramucirumab will be administered simultaneously for non small cell lung cancer patients for 2 cycles before surgery.
Receives: Drug: Pembrolizumab; Drug: Ramucirumab; Procedure: Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Major pathologic response (MPR) rate by central review

    Determination of major pathologic response rate is based on the method by Hellmann et al. on the pathological section. The percentage of residual tumor cells is calculated as viable tumor cells / tumor area × 100 (%). Tumor area includes viable tumor cells and interstitial tissue such as fibrosis, necrosis, and inflammatory cells.

    Measured: 1 year 7 months

Secondary outcomes (7)

  1. Proportion of incidence of adverse events

    The incidences and types of adverse events that occur during neoadjuvant therapy and perioperative period (within postoperative 30 days and 90 days) will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: 1 year 7 months

  2. Major pathological response (MPR) rate by institutional report

    Determination of major pathologic response rate by institutional report

    Measured: 1 year 7 months

  3. Pathological complete response rate (pCR rate)

    Pathological complete response rate (pCR rate)

    Measured: 1 year 7 months

  4. Pathological complete resection rate (R0 rate)

    Pathological complete resection rate (R0 rate)

    Measured: 1 year 7 months

  5. Objective response rate (ORR) according to RECIST and iRECIST

    Objective response rate (ORR) according to RECIST and iRECIST

    Measured: 1 year 7 months

  6. Overall survival (OS)

    Overall survival (OS)

    Measured: 5 years

  7. Recurrence-free survival (RFS)

    Recurrence-free survival (RFS)

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2019
  2. Study start30 Nov 2019
  3. Primary completion20 Apr 2022
  4. Study completion31 Dec 2027 (estimated)

Resources

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
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04040361
Sponsor's protocol ID
EPOC1710
Status last verified
Oct 2026
First submitted
29 Jul 2019
Last updated
2 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Aokage K, Koyama S, Kumagai S, Nomura K, Shimada Y, Yoh K, Wakabayashi M, Fukutani M, Furuya H, Miyoshi T, Tane K, Samejima J, Taki T, Hayashi T, Matsubayashi J, Ishii G, Nishikawa H, Ikeda N, Tsuboi M. Efficacy, Safety, and Influence on the Tumor Microenvironment of Neoadjuvant Pembrolizumab plus Ramucirumab for PD-L1-Positive NSCLC: A Phase II Trial (EAST ENERGY). Clin Cancer Res. 2024 Dec 16;30(24):5584-5592. doi: 10.1158/1078-0432.CCR-24-1561.

    PubMed 39453771

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab, Ramucirumab and Surgery in people with Non-small Cell Lung Cancer Stage IB and Non-small Cell Lung Cancer Stage II, run by National Cancer Center Hospital East at 2 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 11 inclusion and 39 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: under way, not looking for participants, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

This study is still under way. Results are not available in the source record yet.

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?

Major pathologic response (MPR) rate by central review (time frame: 1 year 7 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04040361, which also lists 1 linked publication.

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 2 Nov 2026.

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