Comparing Efficacy and Safety between CT-P16 and EU-approved Avastin in Patients with Metastatic or Recurrent Non-Squamous Non Small Cell Lung Cancer

Phase 1

Conditions: Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
MedDRA version: 20.0Level: LLTClassification code 10079440Term: Non-squamous non-small cell lung cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-002147-28-PT

Lead Sponsor: CELLTRION, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 678

Inclusion Criteria

1. Patient (male or female) must be = 18 years of age.
2. Patient must have confirmed predominantly non-squamous non-small cell lung cancer (nsNSCLC) by hematoxylin and eosin staining and immunohistochemistry.
3. Patient must be diagnosed as recurrent disease or stage IV according to the American Joint Committee on Cancer (AJCC) Lung Cancer Staging 8th edition. Stage IV is defined as below:
a. Separate tumor nodule(s) in a contralateral lobe, or
b. Tumor with pleural or pericardial nodules, or
c. Malignant pleural or pericardial effusion related to tumor, or
d. Single or multiple extrathoracic metastases in a single organ or in multiple organs
4. Patient must have at least 1 measurable lesion by Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1. Target lesions situated in a previously irradiated area are considered measurable if recurrence has been demonstrated in such lesions.
a. Tumor lesions: = 10 mm in long axis by computerized tomography (CT) scan, or
b. Malignant lymph nodes: = 15 mm in short axis by CT scan
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy > 6 months based on clinical judgement.
7. Negative result in both epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement which is confirmed by biopsy or cytology specimens.
8. Patient must have adequate organ function as follows. These tests must be performed within 14 days prior to Day 1 of Cycle 1.
Bone marrow reserve:
a. Hemoglobin = 9.0 g/dL, and
b. Absolute neutrophil count = 1,500/mm3, and
c. Platelet count = 100,000/mm3
Hepatic:
a. Alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase = 3.0 × upper limit of normal (ULN) (= 5.0 × ULN with liver metastasis), and
b. Total bilirubin = 1.5 × ULN
Renal:
a. Serum creatinine = 1.5 × ULN, and
b. Creatinine clearance (CrCl) rate = 45 mL/min, and
c. Urine dipstick for proteinuria < 1+ (i.e., either 0 or trace); if urine dipstick is = 1+ then < 1.0 g of protein in 24 hours urine collection must be confirmed to allow participation in the study
9. Patient and their partner of childbearing potential must agree to use acceptable birth control methods throughout the study and for 6 months after the last dose of assigned treatment (see Section 6.5.2.8).
Aman or woman is of childbearing potential if, in the opinion of the investigator, he or she is biologically capable of having children and is sexually active. Male and female patients and their partners who have been surgically sterilized for less than 24 weeks prior to the date of informed consent must agree to use any medically acceptable methods of contraception. Menopausal females must have experienced their last period more than 1 year prior to the date of informed consent to be
classified as not of childbearing potential.
10. Patient has the ability to comprehend the full nature and purpose of the study, including possible risks and side effects, to cooperate with the investigator, to understand verbal and/or written instructions, and to comply with the requirements of the entire study.
11. Patient and/or their legally authorized representative must be informed and given ample time and opportunity to read and/or understand the nature and purpose of this study and must sign the informed consent form before any study specific procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (1

Exclusion Criteria

1. Patient who has predominantly squamous cell histology non-small cell lung cancer (NSCLC). If small cell elements are present, the patient is ineligible.
2. Patient who has clinically significant third-space fluid; for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to Day 1 of Cycle 1.
3. Patient who has untreated central nervous system (CNS) metastases or CNS metastasis with bleeding risk at investigator's discretion and/or leptomeningeal disease. However, treated and clinically stable (asymptomatic;off steroids) brain metastases are allowed.
4. Patient who has invasion of major blood vessels. Patient with a tumor cavitation in the opinion of the investigator is likely to bleed will be excluded as well.
5. Patient who has received previous anti-cancer systemic therapy including one or more of the following(s):
a. Cytotoxic chemotherapy for metastatic nsNSCLC,
b. Cytotoxic chemotherapy for non-metastatic nsNSCLC within 12 months prior to Day 1 of Cycle 1,
c. Anti-neoplastic biological therapy, immunotherapy or targeted therapy,
d. Bevacizumab (or a bevacizumab proposed biosimilar product).
6. Patient who has received previous surgical procedure including one or more of the following(s):
a. Surgery for metastatic nsNSCLC,
b. Surgery for non-metastatic nsNSCLC within 6 months prior to Day 1 of Cycle 1,
c. Open biopsy or open pleurodesis within 28 days prior to Day 1 of Cycle 1,
d. Core biopsy or other minor surgical procedure (e.g. placement of vascular access device, closed pleurodesis, thoracentesis, and mediastinoscopy) within 14 days prior to Day 1 of Cycle 1.
7. Patient who has received previous anti-cancer radiotherapy including one or more of the following(s):
a. Radiotherapy for metastatic nsNSCLC, but radiotherapy as part of the palliative therapy and/or treatment for CNS metastases completed at least 14 days prior to day 1 of Cycle 1 is allowed,
b. Radiotherapy for non-metastatic nsNSCLC within 6 months prior to Day 1 of Cycle 1,
c. Any toxicity related with radiotherapy prior to Day 1 of Cycle 1.
8. Patient who has a medical history of disease including one or more of the following(s):
a. Clinically significant allergic reactions such as asthma, urticaria, angio-oedema, and eczematous dermatitis, hypersensitivity to any component of carboplatin, paclitaxel, bevacizumab and Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanized
antibodies.
b. Cardiac, gastrointestinal, renal, hepatic, hematological (including pancytopenia, aplastic anemia or blood dyscrasia), metabolic (including known diabetes mellitus), autoimmune disease, or pulmonary diseases classed as significant in the opinion of the investigator.
c. A known infection with hepatitis B (active or carrier of hepatitis B), hepatitis C, or infection with human immunodeficiency virus (HIV). However, a patient with past hepatitis B virus is allowed if resolved.
d. New York Heart Association (NYHA) class 2, severe uncontrolled cardiac disease (unstable angina, clinically significant elctrocardiogram [ECG] abnormalities, ect.), or myocardial infarction, within 6 months prior to Day 1 of Cycle 1.
e. Malignancy or history of malignancy other than NSCLC in the past 5 years except adequately treated squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix.
f. Any recent infection requiring a course of systemic anti-infectives or a serious infection (as

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate CT-P16 is similar to EU-Approved Avastin in terms of efficacy as determined by ORR up to Cycle 6 during the Induction Study Period;Secondary Objective: • To evaluate additional efficacy profiles including ORR during the Whole Study Period, response duration, time to progression (TTP), PFS, and OS<br>• To evaluate the PK of trough serum concentration (Ctrough)<br>• To evaluate safety profile including immunogenicity<br>• To evaluate quality of life (QoL);Primary end point(s): The primary efficacy endpoint will be the ORR based on BOR during the Induction Study Period by RECIST v.1.1.;Timepoint(s) of evaluation of this end point: The primary endpoint will be eavluated up to Cycel 6 during the induction study period

Secondary Outcome Measures

Name	Time	Method

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