Health Condition 1: C34- Malignant neoplasm of bronchus andlung
Conditions
Interventions
Intervention1: Nivolumab: The test drug is a Biosimilar Nivolumab at a concentration of 100 mg/10 mL in a single dose vial. Nivolumab will be administered via intravenous infusion at a dose of 240 mg
Sponsors
Shilpa Biologicals Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Participants of either gender greater than or equal to 18 and less than or equal to 75 years of age. 2. Participants capable and willing to voluntarily provide informed consent for participation as per the locally applicable regulations. 3. Participants must be willing and able to comply with the study requirements. 4. Participants with ECOG performance status score of 0, 1 or 2. 5. Participants with histologically- or cytologically-documented NSCLC who present with Stage IIIB or Stage IIIC or Stage IV disease, or with recurrence or progressive disease following platinum-based chemotherapy. 6. Participants with at least 1 radiographically measurable lesion as per RECIST 1.1 criteria 7. Participants with PD-L1 expression grater than equal to 1 percentage (Tumor Proportionality Score-TPS) 8. Laboratory values must meet the following criteria for adequate bone marrow function: A. Total WBC count greater than or equal to 2000 per mm3, B. ANC greater than or equal to 1500 per mm3, C. Platelet count greater than or equal to 1,00,000 per mm3, D. Haemoglobin greater than or equal to 9.0 g per dL. 9. Laboratory values must meet the following criteria for appropriate renal and liver function status: A. Serum creatinine of less than or equal to 1.5 X ULN or creatinine clearance greater than 40 mL/minute (using Cockcroft/Gault formula); Female CrCL = (140 - age in years) X weight in kg X 0.85/72 X serum creatinine in mg per dL; Male CrCl = (140 - age in years) X weight in kg X 1.00/72 X serum creatinine in mg per dL B. AST less than or equal to 3 X ULN, ( less than or equal to 5 X ULN for liver metastasis) C. ALT less than or equal to 3 X ULN, ( less than or equal to 5 X ULN for liver metastasis) D. Total bilirubin less than or equal to 1.5 X ULN E. aPTT less than or equal to 1.5 X ULN F. INR less than 1.5 10. Prior radiotherapy or radiosurgery must have been completed at least 2 weeks prior to randomization (if administered). 11. Woman of childbearing potential should have a negative pregnancy test at screening and randomization; and should agree to use two highly effective methods of birth control (see list in the Note below) and not to donate or cryopreserve ova during the course of study treatment and for at least 12 months after the last administration of study treatment. Non-pregnant women and women who are not breast feeding will be eligible for the study 12. Sexually active male participants, unless permanently sterile by bilateral orchidectomy or successful vasectomy, who agree to use highly effective methods such as condoms, combined with an additional highly effective method in his female partner (see list in the Note below) and not to donate or cryopreserve sperm during the course of study treatment and for at least 12 months after the last administration of study treatment.
Exclusion criteria
Exclusion criteria: 1. Participants with CNS metastases 2. Participants with carcinomatous meningitis. 3. Participants with a known active or suspected autoimmune disease. Participants with type I diabetes mellitus, autoimmune hypothyroidism controlled with thyroid hormone replacement, autoimmune skin disorders (such as vitiligo, psoriasis, or immune mediated alopecia) not requiring systemic treatment and participants whose autoimmune conditions having well identified and avoidable triggers are permitted to enroll. 4. Participants with any condition requiring systemic treatment with either corticosteroids (higher than 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization and throughout the study period. Note: Topical, ocular, otological, intra-articular, intranasal, and inhalational corticosteroids are permitted. Adrenal substitutive glucocorticoids are allowed even at doses higher than 10 mg daily prednisone (or equivalent) if needed due to stress, in the absence of active autoimmune disease. 5. Participants with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. 6. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 7. Any other active malignancy requiring concurrent intervention. 8. History of previous malignancies except non-melanoma skin cancers, or in situ cervical or breast cancer unless a complete remission was achieved at least 2 years prior to randomization AND no additional therapy is required during the study period. 9. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (NCI-CTCAE, Version 6.0 or a recent version) or baseline before administration of study drug. 10. Participants must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment. 11. History of or current abuse of alcohol or illegal drugs (testing not required). 12. Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). 13. Positive test for hepatitis B virus (HBsAg) or hepatitis C virus other than positive hepatitis B surface antibody test in vaccinated participants. 14. History of allergy or intolerance (unacceptable adverse event) to study drug components 15. History of severe hypersensitivity reactions to other monoclonal antibodies. 16. Ongoing or planned administration of anti-cancer therapies other than those specified in this study. 17. Received any other investigational intervention or used an invasive investigational medical device within 30 days or 5 half-lives prior to the first dose of study intervention, whichever is longer, or is currently enrolled in an investigational study. 18. Any other serious or uncontrolled medical disorder, active infection, physical examination finding, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a participantâ??s ability to comply with the study requirements, substantially increase risk to the participant, or impact the interpretability of study results. 19. Have a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. To assess the pharmacokinetic equivalence of Biosimilar Nivolumab IV infusion as compared to Reference Nivolumab IV infusion 2. To compare the efficacy of Biosimilar Nivolumab IV infusion versus Reference Nivolumab IV infusion in Participants with locally advanced or metastatic non-small cell lung cancer.Timepoint: 1. a. AUCtau,sd at Cycle 1 (Single dose) [Time Frame: Day-1 to Day-14] Area under the concentration-time curve for one dosing interval (tau=14 days) after a single (initial) dose (AUCtau,sd) of SBPL-Nivolumab Biosimilar and Reference Nivolumab (Cycle 1) b. AUCtau,ss at Cycle-6 (Steady State) [Time Frame: Day-71 to Day-85] Area under the concentration-time curve for one dosing interval (tau=14 days) at steady state (AUCtau,ss) of SBPL-Nivolumab Biosimilar and Opdivo® (Cycle 6). 2. Objective Response Rate (i.e., complete response [CR] + partial response [PR]) using Response Evaluation Criteria in Solid Tumours: Revised RECIST guideline (Version 1.1) at the end of Cycle 8 (Day 113). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To assess the secondary pharmacokinetics of Biosimilar Nivolumab IV infusion as compared to Reference Nivolumab IV infusion 2. To assess the immunogenicity of Biosimilar Nivolumab IV infusion as compared to Reference Nivolumab IV infusion 3. To compare the safety & tolerability in Participants exposed to the investigational medicinal products 4. To compare the progression free survival (PFS) of Biosimilar Nivolumab IV infusion with ReferenceTimepoint: 1. Evaluate Secondary PK of Biosimilar Nivolumab as compared to Reference Nivolumab infusion. cycle 1 to cycle 8 2. Compare the ADA & NAbs between participants of Biosimilar Nivolumab & Reference Nivolumab. cycle 1 to cycle 8 3. Compare the AEs, AESI, TEAEs, & SAEs between participants randomized to Biosimilar Nivolumab & Reference Nivolumab. cycle 1 to cycle 12 4. Compare Progression Free Survival between participants of SBPL-Nivolumab Biosimilar & Reference Nivolumab. cycle 1 to cycle 12 | — |
Countries
India
Contacts
Public ContactDr P Veerendra Kumar
Shilpa Biologicals Private Limited
Outcome results
None listed