A Study of LY01008 and Bevacizumab Combined With Paclitaxel and Carboplatin for Treatment of Naïve Subjects With Metastatic or Recurrent Nonsquamous Non-small Cell Lung Cancer

NCT03533127 | Unknown Phase 3

• 1 other identifier: LY01008
• Study Type: interventional
• Target: 648
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Randomized, Double-blind, Multicenter Phase III Study Comparing Efficacy and Safety of LY01008 (Recombinant Humanized Anti-Human Vascular Endothelial Growth Factor Monoclonal Antibody Injection) and Bevacizumab Combined with Paclitaxel and Carboplatin for Treatment of Naïve Subjects with Metastatic or Recurrent Nonsquamous Non-small Cell Lung Cancer

Conditions

Non Small Cell Lung Cancer; Non Small Cell Lung Cancer Metastatic; Non Small Cell Lung Cancer Recurrent

Outcome Measures

Primary Outcomes (1)

• Best Objective Response Rate

  19 weeks from randomization

Secondary Outcomes (2)

• Progression Free Survival

  from the date of randomisation to the date of disease progression or death up to 12 months from randomisation of the last subject

• Overall Survival

  from the date of randomisation to the date of death up to 12 months from randomisation of the last subject

Study Arms (2)

LY01008+Carboplatin/Paclitaxel

EXPERIMENTAL

Drug: LY01008 15 mg/kg IV every 3 weeks on Day 1 Drug: Carboplatin Carboplatin AUC 6 IV every 3 weeks on Day 1 for 4-6 cycles Drug: Paclitaxel Paclitaxel 175 mg/m2 IV every 3 weeks on Day 1 for 4-6 cycles

Drug: LY01008

Bevacizumab + Carboplatin/Paclitaxel

EXPERIMENTAL

Drug: Bevacizumab Bevacizumab 15 mg/kg IV every 3 weeks on Day 1 Drug: Carboplatin Carboplatin AUC 6 IV every 3 weeks on Day 1 for 4-6 cycles Drug: Paclitaxel Paclitaxel 175 mg/m2 IV every 3 weeks on Day 1 for 4-6 cycles

Drug: Bevacizumab

Interventions

LY01008 DRUG

LY01008+Carboplatin/Paclitaxel

LY01008+Carboplatin/Paclitaxel

Bevacizumab DRUG

Bevacizumab + Carboplatin/Paclitaxel

Bevacizumab + Carboplatin/Paclitaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has voluntarily signed the written informed consent form (ICF)
• Male or female patients aged 18 to 75 years (18 years and 75 years are inclusive)
• The patients with metastatic (stage IV) or recurrent nonsquamous NSCLC proved by histological or cytological demonstrated who cannot have surgical treatment. The diagnosis result of nonsquamous NSCLC obtained only based on the sputum cytology is not accepted. If the patient has many kinds of tumor components, the main cell types should be classified；
• The patient should have at least one measurable lesion as the target lesion (according to RECIST 1.1 criteria)；
• The Eastern Cooperative Oncology Group (ECOG) performance status score is 0 to 1 point.
• The predictable survival duration is ≥ 6 months
• Laboratory results during screening:
• Blood routine: white blood cell count ≥ 3.0× 109/L, absolute neutrophil count ≥ 1.5× 109/L, platelet count≥ 100× 109/L and hemoglobin≥ 90 g/L.
• Liver function: Total bilirubin \<1.5×upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5×ULN for the subjects without liver metastasis and ALT and AST\< 5×ULN for the subjects with liver metastasis.
• Kidney function: Serum creatinine ≤ 1.5 ×ULN or creatinine clearance rate ≥ 50 mL/min and urine protein \<2+ ( quantitative test for 24h urine protein should be conducted when the baseline urine protein is 2+ and the subject can only be enrolled when the 24 h urine protein quantitation is ≤ 1 g );
• The international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT or aPTT) ≤ 1.5 × ULN within 7 days before the study treatment
• The subject can comply with the study protocol.
• The female subjects and male subjects of childbearing age and the partners of the male subjects agree to take reliable contraceptive measures (such as abstinence, sterilizing operation, contraceptives, injection of the contraceptive drug medroxyprogesterone acetate or subdermal implant of contraceptives

You may not qualify if:

• The patients who have received chemotherapy or other systemic antineoplastic therapy drugs (such monoclonal antibodies and tyrosine kinase inhibitors) for the disease of the current stage (stage IV or recurrent disease). The patients are allowed to have received past surgery and radiotherapy, but they must meet the criteria for the related two treatment methods listed in the study protocol. The subjects who have recurrented after adjuvant/ neoadjuvant chemotherapy can also be enrolled if the interval between the completion time of the adjuvant/ neoadjuvant therapy and the administration time of the initial dose of the study is more than 6 months；
• The subjects with mixed NSCLC which containing small cell cancer component or the squamous-cell carcinoma component dominant；
• The patient has history of hemoptysis within 3 months before screening and the expectorated fresh blood is ≥ 2.5 mL.
• The images reveal sign of tumor invasion in great vessels. The subjects with tumor completely closes to, surrounds or invades the lumen of great vessels (such as pulmonary artery or superior vena cava) must be excluded;
• The subjects with symptomatic brain metastasis, a history of spinal cord compression or meningeal metastases and subjects who have previously received brain metastasis treatment, if their lesion is radiographically confirmed to have remained stable for more than 4 weeks at screening, can be enrolled；
• The subjects who have received radical thoracic radiotherapy within 28 days before enrollment and the subjects who have received palliative radiotherapy for the bone lesions besides chest within 2 weeks before the treatment with the first dose of study drugs；
• The subjects who have had major surgery, major trauma (such as fracture) within 28 days before randomization or the subjects who are expected to have major surgery during the study cycle ；
• The patients who are taking or have taken aspirin (\>325 mg/day) or other non-steroidal anti-inflammatory drugs which are known to be able to inhibit platelet function recently (within 10 days before receiving the initial dose of the study drugs)；
• The patients who are taking or have taken whole dose oral or parenteral anticoagulation drugs or thrombolytic agents recently (within 10 days before receiving the initial dose of the study drugs). However, the patients are allowed to have preventive use of anticoagulation drugs；
• The patients who have inherited bleeding tendency or coagulation disorders；
• The patient with thrombotic diseases which revealed by medical history or examination results within 6 months before enrollment；
• The patient with uncontrolled hypertension (systolic pressure is more than 150 mmHg and/or diastolic pressure is more than 100 mmHg), hypertensive crisis or history of hypertensive encephalopathy;
• The patient with any unstable systemic disease: including but not limited to unstable angina pectoris, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade II), serious arrhythmia，liver, kidney or metabolic diseases that need drug treatment,
• The patient with serious unhealed wound and gastrointestinal ulcer. Medical history of the following diseases within 6 months before screening: gastrointestinal perforation, corrosive esophagitis or gastritis, inflammatory bowel disease or diverticulitis, abdominal fistula or intra-abdominal abscess.
• The patient with tracheo-esophageal fistula；

Sponsors & Collaborators

• Luye Pharma Group Ltd.: lead

Study Sites (1)

Chinese Academy of Medical Sciences

Chaoyang, Beijing Municipality, 100021, China

RECRUITING

Related Publications (1)

• Shi Y, Lei K, Jia Y, Ni B, He Z, Bi M, Wang X, Shi J, Zhou M, Sun Q, Wang G, Chen D, Shu Y, Liu L, Guo Z, Liu Y, Yang J, Wang K, Xiao K, Wu L, Yi T, Sun D, Kang M, Ma T, Mao Y, Shi J, Tang T, Wang Y, Xing P, Lv D, Liao W, Luo Z, Wang B, Wu X, Zhu X, Han S, Guo Q, Liu R, Lu Z, Zhang J, Fang J, Hu C, Ji Y, Liu G, Lu H, Wu D, Zhang J, Zhu S, Liu Z, Qiu W, Ye F, Yu Y, Zhao Y, Zheng Q, Chen J, Pan Z, Zhang Y, Lian W, Jiang B, Qiu B, Zhang G, Zhang H, Chen Y, Chen Y, Duan H, Li M, Liu S, Ma L, Pan H, Yuan X, Yuan X, Zheng Y, Gao E, Zhao L, Wang S, Wu C. Bevacizumab biosimilar LY01008 compared with bevacizumab (Avastin) as first-line treatment for Chinese patients with unresectable, metastatic, or recurrent non-squamous non-small-cell lung cancer: A multicenter, randomized, double-blinded, phase III trial. Cancer Commun (Lond). 2021 Sep;41(9):889-903. doi: 10.1002/cac2.12179. Epub 2021 Jun 29.

  PMID: 34184418 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab

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

Central Study Contacts

Can Wu

CONTACT

13811253790; wucan@luye.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The subjects will receive the treatment with LY01008 or bevacizumab combined with paclitaxel and carboplatin for 4-6 cycles, and then both groups of subjects will receive the maintenance monotherapy with LY01008

Study Record Dates

• First Submitted: May 10, 2018
• First Posted: May 22, 2018
• Study Start: November 27, 2017
• Primary Completion: June 28, 2020
• Study Completion: December 28, 2020
• Last Updated: July 10, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)