Health Condition 1: null- non-squamous Non-Small-Cell Lung Cancer (nsNSCLC)
Conditions
Interventions
Intervention1: CBT124: Cipla BioTec biosimilar bevacizumab
25mg/mL strength
intravenous infusion
Control Intervention1: Avastin(registered mark) sourced from EU: Bevacizumab
intravenous infusion
Sponsors
Cipla BioTec Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1. Adult subjects aged >= 18 to 75 years (>= 18 to 65 years for India) with histologically or cytologically confirmed advanced non-squamous NSCLC. Mixed tumors should be categorized according to the predominant histology 2. Epidermal growth factor receptor (EGFR) negative (for example, deletion exon 19 or exon 21 point mutation L858R) or wild type mutations 3. No Kirsten rat sarcoma viral oncogene homolog (KRAS) and anaplastic lymphoma receptor tyrosine kinase (ALK) positive subjects 4. Stage IV (Unresectable recurrent disease or metastatic) NSCLC 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 6. Evaluable disease status or measurable tumor 7. Life expectancy > 6 months. 8. Adequate hepatic, renal, and bone marrow function (alanine aminotransferase [ALT] and aspartate aminotransferase [AST] bilirubin >= 60 mL/min; urine dipstick = 1500/mm3; platelet count >= 105/mm3; hemoglobin >= 9 g/dL). Subjects with a 1+ or greater urine dipstick reading should undergo further assessment as per the clinical judgement of the Investigator, including 24 hours urine collection or a laboratory protein/creatinine index in urine (with quantitative protein determination in a full sized sample even if not necessarily a 24 hours collection), as needed. Urinary protein should be hours or protein/creatinine index of less than 0.2 mg/mgCreatinine or 15 mg/mmol Creatinine. 9. Subjects with pre-existing hypertension must be well controlled on a stable regimen of antihypertensive therapy. Have systolic blood pressure = 90 mmHg, diastolic blood pressure = 50 mmHg and heart rate >= 40 and admission. For single measurements in the 141 to 160 mmHg range (systolic) or in the 91 to 100 mmHg range (diastolic), a single repetition after resting for a few minutes (e.g. 5 minutes) on a supine position on the same day is allowed and, in this case, the mean of both measurements will guide eligibility. The mean of both the measurements should be 10. Ability to understand risks of participation in the study and willingness provide informed consent.
Exclusion criteria
Exclusion criteria: 1. Small cell lung cancer (SCLC) or combination of SCLC and NSCLC. Squamous-cell tumors and mixed adenosquamous carcinomas of predominantly squamous nature 2. Known sensitizing EGFR mutations (for example, deletion exon 19 or exon 21 point-mutation L858R) or EML4-ALK translocation-positive mutations. Subjects with KRAS mutations 3. Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGF receptors, including bevacizumab 4. Prior therapy with carboplatin or paclitaxel 5. Prior systemic therapy for metastatic disease. Prior systemic anticancer therapy or radiotherapy for locally-advanced NSCLC if completed 6. Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation that in the opinion of the Investigator is likely to bleed 7. Symptomatic brain metastasis (head computed tomography [CT]/magnetic resonance imaging [MRI] is required within 6 weeks of study randomization) 8. Previous malignancy other than NSCLC in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix 9. Any unresolved toxicity > Common Toxicity Criteria Grade 1 (except alopecia) from previous anticancer therapy (including radiotherapy) 10. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding. Thrombotic or hemorrhagic event 11. History of hemoptysis greater than ½ teaspoon of bright red (fresh) blood in the past 4 weeks 12. Subjects receiving long-term aspirin ( > 325 mg/day), or other non-steroidal anti-inflammatory agents, or other drugs known to inhibit platelet function, treatment with dipyridamole, ticlopidine, or clopidogrel 13. Subjects receiving anticoagulants 14. Subjects who plan to undergo surgery during the study period 15. Subjects who have undergone a major surgery, or have had a significant traumatic injury within 4 weeks prior to randomization 16. Subjects who have a significant non-healing wound, or bone fracture within 4 weeks prior to randomization 17. Subjects with history of gastrointestinal perforation or fistula formation 18. Subjects with known hypersensitivity to any of the ingredients of the investigational products, or mammalian cell-derived products 19. Female subjects who are pregnant, breast-feeding, planning to be pregnant during the study, or women of child-bearing potential (any woman who is not surgically sterile i.e., bilateral tubal ligation, total hysterectomy or reliable method of double contraception (e.g. condom plus diaphragm, condom or diaphragm plus spermicidal gel/foam, tubal ligation, or stable dose of hormonal contraception) throughout the study period 20. Male subject with a partner of childbearing potential (as mentioned in exclusion criteria 19) who does not consent to the use of a reliable method of double contraception (as mentioned in exclusion criteria 19) 21. Subjects with uncontrolled hypertension 22. Subjects with active infection assessed to be clinically significant by Investigator 23. Known history of, or positive test result for human immunodeficiency virus (HIV)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) per RECIST criteria version 1.1.Objective response rate is defined as the proportion of subjects whose best confirmed overall response over Week 1 to Week 19 is either complete response (CR) or partial response (PR). Confirmed best overall response (complete or partial response) may be claimed only if the criteria for each are met after a repeat radiologic tumor assessment (using RECIST criteria version 1.1) 6 weeks later.Timepoint: 19 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy: Progression-free survival (PFS) rate Overall Survival (OS) rate Duration of responseTimepoint: PFS - 1 year OS - 1 year;Pharmacokinetics: Secondary PK parametersTimepoint: Cycle 1 (Cmax) Cycle 2-6 (Ctrough);Safety (Proportion of subjects with selected adverse events (AE) of gastrointestinal perforation, hypertension, proteinuria, and pulmonary hemorrhage)Timepoint: 19 weeks and EoS | — |
Countries
Bulgaria, Hungary, India, South Africa, Ukraine
Contacts
Public ContactSandesh Sawant
Cipla BioTec Pvt. Ltd.
Outcome results
None listed