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

NCT04040361 | Unknown Phase 2

• 1 other identifier: EPOC1710
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Non-small Cell Lung Cancer Stage IB; Non-small Cell Lung Cancer Stage II; Non-small Cell Lung Cancer Stage ⅢA

Outcome Measures

Primary Outcomes (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.

  1 year 7 months

Secondary Outcomes (7)

• Proportion of incidence of adverse events

  1 year 7 months

• Major pathological response (MPR) rate by institutional report

  1 year 7 months

• Pathological complete response rate (pCR rate)

  1 year 7 months

• Pathological complete resection rate (R0 rate)

  1 year 7 months

• Objective response rate (ORR) according to RECIST and iRECIST

  1 year 7 months

Study Arms (1)

Pembrolizumab+Ramucirumab+Surgery

EXPERIMENTAL

Pembrolizumab and Ramucirumab will be administered simultaneously for non small cell lung cancer patients for 2 cycles before surgery.

Drug: Pembrolizumab; Drug: Ramucirumab; Procedure: Surgery

Interventions

Pembrolizumab DRUG

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

Also known as: MK3475

Pembrolizumab+Ramucirumab+Surgery

Ramucirumab DRUG

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

Also known as: LY3009806

Pembrolizumab+Ramucirumab+Surgery

Surgery PROCEDURE

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

Pembrolizumab+Ramucirumab+Surgery

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Masahiro Tsuboi: lead
• Merck Sharp & Dohme LLC: collaborator
• Eli Lilly and Company: collaborator

Study Sites (2)

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

RECRUITING

Tokyo Medical University Hospita

Shinjuku-Ku, Tokyo, Japan

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Ramucirumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Masahiro Tsuboi, Dr

  National Cancer Center Hospital East

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Masahiro Tsuboi, Dr

CONTACT

+81-4-7133-1111; energy@east.ncc.go.jp

Keiju Aokage, Dr

CONTACT

+81-4-7133-1111; energy@east.ncc.go.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Division of Thoracic Surgery

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: July 31, 2019
• Study Start: November 30, 2019
• Primary Completion: April 30, 2022
• Study Completion: November 30, 2025
• Last Updated: April 6, 2022

Record last verified: 2022-04

Locations

JP (2)