Non-squamous Non-small Cell Lung Cancer (nsNSCLC) MedDRA version: 20.0 Level: LLT Classification code 10079440 Term: Non-squamous non-small cell lung cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: bevacizumab biosimilar
Product Code: HD204
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Bevacizumab Biosimilar
Current Sponsor code: HD204
Other descriptive name: BEV
Sponsors
Prestige BioPharma Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to give written informed consent. 2. Aged = 18 years of age. 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 and life expectancy >3 months based on Investigator’s judgement. 4. Histologically confirmed metastatic Stage IV or recurrent non squamous non-small cell lung cancer (NSCLC) that is no longer amendable to curative surgery or local therapy. 5. At least one measurable lesion according to RECIST v.1.1. as confirmed by CIR; bone-only and brain-only metastases are not allowed. Lesions previously treated with radiotherapy are non-target lesions unless clear progression was documented. Previous results are acceptable if performed within 4 weeks prior to screening. 6. No first line treatment for metastatic or recurrent disease. Prior systemic therapy and/or radiotherapy for locally advanced disease is permitted if completed = 6 months prior to the diagnosis of relapsing disease. 7. Tumors without EGFR mutation or ALK receptor alteration. Patients with unknown mutation status or known EGFR mutation or ALK receptor alteration may be included provided the corresponding targeted agent is not available and chemotherapy is the standard of care of the study center. 8. Adequate hematological function, defined as: a. Platelet count: =100,000/µL without the need for transfusion in the 2 weeks prior to Screening. b. Prothrombin time (PT), International normalized ratio (INR) or activated partial thromboplastin time (aPTT) =1.5 x the upper limit of normal (ULN). c. Absolute neutrophil count: =1,500/µL without any medical interventionaltreatment (ie, granulocyte-colony stimulating factors [G-CSFs] and/or herbal remedies). d. Hemoglobin: =9 g/dL, without the need for transfusion in the 2 weeks prior to Screening. 9. Adequate hepatic function as evidenced by meeting all of the following requirements: a. Total bilirubin: = 1.5 x ULN. b. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP): = 3 x ULN. c. If liver metastases are present, ALT and AST = 5 x ULN; if liver and/or bone metastases are present ALP = 5 x ULN. 10. Adequate renal function, as evidenced by meeting all of the following requirements: a. Serum creatinine = 1.5 x ULN and creatinine clearance > 50 mL/minute or estimated glomerular filtration rate (GFR) >50 mL/minute. b. Urine dipstick for proteinuria of less than 2+ (other ways of urinalysis are also acceptable); if urine dip stick is = 2+, proteinuria must be =65 years) yes F.1.3.1 Number of subjects for this age range 130
Exclusion criteria
Exclusion criteria: 1. Diagnosis of small cell carcinoma of the lung or mixed tumors including small cell carcinoma. 2. Known ROS-1 positive tumor, except in scenarios where the corresponding target agent is not available, and chemotherapy is the standard of care at the study center. Patients with ROS-1 status not known at all can be considered as eligible for the study. 3. Tumor cavitation, tumor invading into large blood vessels or close to large vessels with high risk of bleeding, according to Investigator's judgment. 4. Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGFR. 5. Prior systemic anticancer therapy, or radiotherapy for locally advanced nsNSCLC if completed Grade I (except alopecia) from previous anticancer therapy (including radiotherapy). 9. History of hemoptysis (> 1/2 teaspoon per event over the past 6 months) or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding. Clinically non-significant minor bleeding is acceptable. 10. A significant thrombotic or hemorrhagic event = 6 months prior to Screening (includes hemoptysis [> 2.5 mL of red blood], gastrointestinal bleeding, hematemesis, CNS hemorrhage, severe epistaxis or vaginal bleeding, cerebral infarction, transient ischemic attacks, myocardial infarction, unstable angina, and uncontrolled coronary artery disease). 11. Clinically serious non-healing wounds, or incompletely healed bone fracture at screening. 12. Known hypersensitivity to any of the study drugs or their excipients, or history of clinically significant atopic allergy (eg, asthma including childhood asthma, urticarial). 13. Live/attenuated vaccine within 12 weeks prior to the Screening Visit. 14. History of myocardial infarction (= 6 months prior to Screening), unstable angina, New York Heart Association Grade II or greater, congestive heart failure, or serious cardiac arrhythmia requiring medication. 15. History of poorly controlled hypertension or resting blood pressure >150/100 mmHg in the presence of a stable regimen of antihypertensive therapy. 16. Any major surgical procedure (risk of bleeding or wound healing complications) within 28 days prior to the screening. 17. History of active gastroduodenal ulcer, abdominal fistula as well as nongastrointestinal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to Screening. However, patient with history of ulcer which had been treated could be considered as eligible for the study. 18. Clinically significant active infection requiring systemic therapy. 19. Known active Hepatitis B infection (according to local site standards) or active Hepatitis C infection (Hepatitis C virus [HCV] antibody p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate clinical equivalence of the bevacizumab biosimilar (HD204) to reference bevacizumab (EU-Avastin®) given with chemotherapy by comparing the overall response rate (ORR) at Week 18 in Patients with Metastatic or Recurrent Non-squamous Non-small Cell Lung Cancer.;Secondary Objective: • To compare ORR at Week 6 and Week 12 between the bevacizumab biosimilar (HD204) and reference bevacizumab (EU-Avastin®). • To compare ORR at Week 18 adjusted on dose intensity. • To compare the efficacy of bevacizumab biosimilar (HD204) to reference bevacizumab (EU-Avastin®) in terms of duration of response (DoR), progression-free survival (PFS) and overall survival (OS). • To compare the change in tumour burden from baseline as measured by the sum of longest diameters (SLD) of the target lesions. •To compare the safety and immunogenicity of bevacizumab biosimilar (HD204) and reference bevacizumab (EU-Avastin®). • To compare bevacizumab PK parameters after administration of bevacizumab biosimilar (HD204) and reference bevacizumab (EU-Avastin®).;Primary end point(s): Overall response rate (ORR) at Week 18. The response is evaluated according to RECIST version 1.1, as assessed by the central, independent, blinded radiologist.;Timepoint(s) of evaluation of this end point: Week 18 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: -ORR at Week 6 and Week 12 of the bevacizumab biosimilar (HD204) and reference bevacizumab (EU-Avastin®). - ORR at Week 18 adjusted on dose intensity. - Progression free Survival rate (PFS) at 12 months. - Progression free Survival time (time from randomization to date of documented clinical or radiological progression or death due to any cause). - Change in tumour burden from baseline as measured by the SLD of the target lesions. - Overall survival rate at 12 months. - Overall survival time. - Duration of Response (DOR) (from first documentation of a response (CP or PR) and first documentation of progression according to RECIST 1.1). Safety: Safety assessments will include monitoring for vital sign abnormalities, clinical laboratory abnormalities, physical examination, electrocardiogram parameters, adverse events (AEs; graded as mild, moderate, or severe), serious AEs, and treatment-emergent AEs (TEAEs). Immunogenicity: ADA and NADA correlated with Bevacizumab. Sampling: Baseline,end of cycle 4, end of Cycle 7 and at EoT Pharmacokinetics: Bevacizumab though following treatments of HD204 or EU-Avastin®. Sampling: -Baseline, -Cycle 2 (pre- and 1 hour post- infusion and 5-hour post-infusion); -Cycle 4 (pre- and 1 hour post- infusion and 5-hour post-infusion); -Cycle 6 (pre- and 1 hour post- infusion and 5-hour post-infusion); -EoT.;Timepoint(s) of evaluation of this end point: Efficacy: Week 6, 12 and 18. Month 12 Immunogenicity: Baseline, end of cycle 4, end of Cycle 7, EoT Pharmacokinetics: Baseline, cycle 2, 4, 6 and EoT | — |
Countries
Belarus, Bulgaria, Chile, Croatia, Georgia, Greece, Hungary, India, Latvia, Malaysia, Philippines, Poland, Russian Federation, Serbia, Slovakia, Thailand, Turkey, Ukraine
Contacts
Public ContactProject Manager
Prestige BioPharma Limited
Outcome results
None listed