ung cancer clinical study comparing efficacy, safety and immunogenicity of CBT124 (Bevacizumab Candidate Biosimilar) with EU-sourced Avastin®.

Phase 3

Not yet recruiting

• Conditions: Health Condition 1: null- non-squamous Non-Small-Cell Lung Cancer (nsNSCLC)

• Registration Number: CTRI/2017/02/007805
• Lead Sponsor: Cipla BioTec Pvt Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 24 November 2021

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: Not specified
• Target Recruitment: 200

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] < 2.5 Ã? upper limit of normal [ULN], or ALT and AST

< 5 Ã? ULN, if liver function abnormalities are due to underlying malignancy; total

bilirubin <= 1.5 Ã? ULN; serum creatinine <= 1.5 Ã? ULN or calculated creatinine clearance

>= 60 mL/min; urine dipstick < 1+ [i.e., 0 or traces]; international normalized ratio (INR)

<= 1.5, and partial thromboplastin time <= ULN; absolute neutrophil count >= 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 < 100 mg/24

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 <= 140 and >= 90 mmHg, diastolic

blood pressure <= 90 and >= 50 mmHg and heart rate >= 40 and <= 90 bpm at screening 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

<= 140 mmHg (systolic) and <= 90 mmHg (diastolic).

10. Ability to understand risks of participation in the study and willingness provide informed

consent.

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 < 12 months prior to screening

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 <= 6 months prior to screening

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 < 2 years post menopause) not using a

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)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) per RECIST criteria version 1.1.Objective response rate is defined as the proportion of subjects whose best confirmed overall <br/ ><br>response over Week 1 to Week 19 is either complete response (CR) or partial response (PR). <br/ ><br>Confirmed best overall response (complete or partial response) may be claimed only if the <br/ ><br>criteria for each are met after a repeat radiologic tumor assessment (using RECIST criteria <br/ ><br>version 1.1) 6 weeks later.Timepoint: 19 Weeks

Secondary Outcome Measures

Name	Time	Method
Efficacy: Progression-free survival (PFS) rate <br/ ><br>Overall Survival (OS) rate <br/ ><br>Duration of responseTimepoint: PFS - 1 year <br/ ><br>OS - 1 year;Pharmacokinetics: Secondary PK parametersTimepoint: Cycle 1 (Cmax) <br/ ><br>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