Melanoma
Conditions
Keywords
Neoplasm, Programmed cell death-protein 1(PD-1), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), Monoclonal antibody, Immunoglobulins
Brief summary
The purpose of this study is to investigate the pharmacokinetics (PK) similarity of Bmab1700 (an intended nivolumab biosimilar), compared with United States (US)-licensed Opdivo, in participants after complete surgical removal of melanoma.
Detailed description
This study consists of 2 treatment periods: Double-Blind Treatment Period (DB-TP, Week 0 to Week 24 Predose) and Open-Label Treatment Period (OL-TP, From Week 24 Dosing to Week 52). Participants will be randomized in a ratio of 1:1 ratio to receive intravenous infusion of either Bmab1700 (test) or Opdivo (reference) every 4 weeks (Q4W) in DB-TP until disease relapse or recurrence, unacceptable toxicity, or Week 20, whichever occurs earlier. At Week 24, after completing all pre-dose assessments, participants who will remain on study will receive Bmab1700 Q4W until Week 48 end of treatment (EOT) of OL-TP \[EOT-OL-TP\]. The end-of-study (EOS) for OL-TP (EOS-OL-TP) will then occur at Week 52.
Interventions
DRUGBmab1700
Intravenous infusion.
DRUGOpdivo
Intravenous infusion.
Sponsors
Biocon Biologics UK PLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants greater than or equal to (\>=)18 years of age on the day of signing informed consent (follow local regulatory requirements if the legal age of consent for study participation is \>18 years old). 2. Able to understand and willing to provide consent using the study Informed Consent Form (ICF). The voluntarily signed ICF must be obtained before any study-specific procedures are performed. 3. Histologically or cytologically confirmed Stage IIB, Stage IIC, Stage III, or Stage IV melanoma (per American Joint Committee on Cancer, 8th edition) that was completely surgically resected. Complete surgical resection requires removal of all clinically or radiographically evident regional disease. Completion of lymph node dissection is not required unless clinically indicated. Participants must have been surgically rendered free of disease with negative margins on resected specimens documented by appropriate pathology and surgical reports. 4. Complete surgical resection of melanoma must have been performed within 12 weeks before randomization. 5. All participants must have disease-free status documented by a complete physical examination and imaging studies before randomization. 6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 7. Participants must have recovered from melanoma related surgery and its complications before randomization, as per investigator.
Exclusion criteria
1. History of ocular/uveal melanoma. 2. Participants with an active, known, or suspected autoimmune disease are to be excluded from participation. Participants who have received systemic treatment for an autoimmune disease within the past 2 years before randomization (eg, with disease-modifying agents, corticosteroids, or immunosuppressive drugs) are also excluded. 3. History of active malignancy other than melanoma under study within 3 years before randomization, except for locally curable early-stage cancers (carcinoma in situ or Stage I) that have been curatively treated, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. 4. Participants with a condition requiring systemic treatment with either corticosteroids \>10 mg daily prednisone or equivalent or other immunosuppressive medications within 14 days before randomization. Inhaled or topical steroids, and adrenal replacement steroid doses \<=10 mg daily prednisone or equivalent, are permitted in the absence of active autoimmune disease 5. Female participants who are pregnant or breastfeeding at the screening visit, or who intend to become pregnant or breastfeed at any time during the study and for 150 days after the last dose of study intervention. 6. Use of an investigational agent or an investigational device within 28 days or 5 half-lives (if half-life is known for the investigational agent), whichever is longer, before randomization or have not recovered from AEs associated with such therapies to Grade 1 or below (based on CTCAE Version 6.0). 7. Any antineoplastic therapy after the complete resection of melanoma under study (eg, chemotherapy, radiation therapy, targeted agents, biotherapy, or limb perfusion). 8. Participants who have received a live/attenuated vaccine within 28 days before randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. 9. Expected to receive any other form of antineoplastic therapy during the clinical study. 10. Participants who received previous systemic therapy with any of the following: anti-programmed cell death-protein 1 (PD-1), anti programmed cell death-ligand 1 (PD-L1), anti-programmed cell death-ligand 2 (PD-L2), anti-CD137, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies (including nivolumab or pembrolizumab or ipilimumab or other CTLA-4 targeting agents), chimeric antigen receptor T-cell therapy cells, or any agents targeting the IL-2 pathway or other T-cell co-stimulation/ checkpoint pathways. 11. Treatment with complementary medications (eg, herbal supplements or traditional medicines) with an antineoplastic intent to treat the melanoma within 2 weeks before randomization. Such medications are permitted if they are used as supportive care. 12. Participants will be excluded if clinical assessment or laboratory investigations before randomization demonstrate any of the following: 1. White blood cells: less than (\<) 2000 per microliter 2. Neutrophils: \<1500 per microliter 3. Platelets: \<100 \*103 per microliter 4. Hemoglobin: \<9.0 gram per deciliter (g/dL) 5. Participants with estimated creatinine clearance (CrCl) (measured or calculated) less than or equal to (\<=) 40 milliliter per minute (mL/min). • CrCl: using the Cockroft-Gault formula: * Female CrCl = \[(140 - age in years) \* weight in kilogram (kg) \* 0.85\] divided by (72 \* serum creatinine in milligram per deciliter \[mg/dL\]) * Male CrCl = \[(140 - age in years) \* weight in kg \* 1.00\] divide by (72 \* serum creatinine in mg/dL) 6. Aspartate aminotransferase: greater than (\>) 2.5 \* upper limit of normal (ULN) 7. Alanine aminotransferase: \>2.5 \* ULN 8. Total bilirubin \>1.5 \* ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of \<3.0 \* ULN) 13. Participants positive for human immune deficiency virus (HIV-1 and HIV-2) tests. Screening for HIV infection must adhere to local regulatory guidelines and confirm the absence of HIV-1 and HIV-2 infection. Note: Participants with documented HIV infection may be enrolled where required by local regulatory or ethics committee guidance, provided all the following criteria are met: * The participant is on stable antiretroviral therapy for at least 12 weeks prior to the first dose of study treatment, and no planned change in antiretroviral therapy regimen during the PK sampling period. * Adequate immune function, defined as: CD4+ T cell count greater than or equal to (\>=) 350 cells per millimeter cube (cells/mm\^3) at screening * No history of uncontrolled or recent Acquired Immunodeficiency Syndrome (AIDS) defining illness, that is \[ie\], no active AIDS defining condition within the past 12 months * Undetectable viral RNA load 14. Participants having positive test result for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating presence of virus, eg, hepatitis B surface antigen (Australia antigen) positive, or hepatitis C antibody (anti- HCV) positive (except if HCV RNA negative). 15. Participants with history or current evidence of any clinically significant medical condition (including but not limited to physical examination, vital signs, electrocardiogram \[ECG\] findings, laboratory results), or ongoing therapy, that could confound study results, increase participation risk, or are deemed not in the participant's best interest by the treating investigator. 16. Known history of allergy or hypersensitivity to IMP components. 17. Known history of severe hypersensitivity reaction (Grade \>=3) to any monoclonal antibody. 18. Participants who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness. 19. Has documented or known current alcohol/drug abuse that precludes the participant's ability to adhere to the protocol. 20. Prisoners or participants who are involuntarily incarcerated.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Concentration-Time Curve from Time 0 (Day 1) To Day 29 After the First Dose (AUC0-28days) of Bmab 1700 and Opdivo | Week 0 through Week 4 |
| Area Under the Concentration-Time Curve Over a Dosing Interval (AUC0-tau) of Bmab 1700 and Opdivo | Week 16 through Week 20 |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Observed Serum Concentration (Cmax) of Bmab 1700 and Opdivo | Cycle 1, Days 1 to 22: Predose, 1, 3, 24, 48, 168, 336 and 504 hours after the end of infusion (each cycle is of 28 days) |
| Time to Reach the Maximum Serum Concentration (Tmax) of Bmab 1700 and Opdivo | Cycle 1, Days 1 to 22: Predose, 1, 3, 24, 48, 168, 336 and 504 hours after the end of infusion (each cycle is of 28 days) |
| Maximum Observed Plasma Concentration (Cmaxss) of Bmab 1700 and Opdivo at Steady State | Cycle 5, Days 1 to 22: Predose, 1, 3, 24, 48, 168, 336 and 504 hours after the end of infusion (each cycle is of 28 days) |
| Time to Reach the Maximum Serum Concentration (Tmaxss) of Bmab 1700 and Opdivo at Steady State | Cycle 5, Days 1 to 22: Predose, 1, 3, 24, 48, 168, 336 and 504 hours after the end of infusion (each cycle is of 28 days) |
| Serum Observed Concentration Before Next Dosing (Ctrough) of Bmab 1700 and Opdivo | Cycles 2 to 7, Day 1: At predose (each cycle is of 28 days) |
| Number of Participants with Adverse Events (AEs), serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESIs) | Baseline up to Week 24 |
| Percentage of Participants who Developed Anti-drug Antibodies (ADA) and ADA Titer to Bmab 1700 and Opdivo | Baseline up to Week 24 |
Countries
Georgia, Romania, Serbia, South Africa, Spain, Turkey (Türkiye)
Contacts
CONTACTDharma Rao Uppada, MD
CONTACTRajesh CN
Outcome results
None listed