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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-525158-20-00 | EU Trial (CTIS) Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bmab1700 | Experimental | Participants will receive intravenous infusion of Bmab1700 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 continue to receive Bmab1700 Q4W until Week 48 end of treatment of OL-TP [EOT-OL-TP]. |
|
| Opdivo | Experimental | Participants will receive intravenous infusion of Opdivo Q4W 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 of OL-TP [EOT-OL-TP]. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bmab1700 | Drug | Intravenous infusion. |
| |
| Opdivo |
| Measure | Description | 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 |
| Measure | Description | 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 |
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Inclusion Criteria:
Exclusion Criteria:
History of ocular/uveal melanoma.
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.
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.
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
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.
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).
Any antineoplastic therapy after the complete resection of melanoma under study (eg, chemotherapy, radiation therapy, targeted agents, biotherapy, or limb perfusion).
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.
Expected to receive any other form of antineoplastic therapy during the clinical study.
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.
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.
Participants will be excluded if clinical assessment or laboratory investigations before randomization demonstrate any of the following:
White blood cells: less than (<) 2000 per microliter
Neutrophils: <1500 per microliter
Platelets: <100 *103 per microliter
Hemoglobin: <9.0 gram per deciliter (g/dL)
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:
Aspartate aminotransferase: greater than (>) 2.5 * upper limit of normal (ULN)
Alanine aminotransferase: >2.5 * ULN
Total bilirubin >1.5 * ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of <3.0 * ULN)
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:
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).
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.
Known history of allergy or hypersensitivity to IMP components.
Known history of severe hypersensitivity reaction (Grade >=3) to any monoclonal antibody.
Participants who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Has documented or known current alcohol/drug abuse that precludes the participant's ability to adhere to the protocol.
Prisoners or participants who are involuntarily incarcerated.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Dharma Rao Uppada, MD | Contact | +91 80 2808 5302 | dharmarao.uppada@biocon.com | |
| Rajesh CN | Contact | +91 9725466994 | rajesh.cn@biocon.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| High Technology Hospital Medcenter | Batumi | Georgia |
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| Drug |
Intravenous infusion. |
|
| 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 |
| JSC Vian | Kutaisi | Georgia |
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| Institute of Clinical Oncology - Lubliana Street | Tbilisi | Georgia |
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| Israel-Georgian Medical Research Clinic Helsicore | Tbilisi | Georgia |
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| LTD New Hospitals | Tbilisi | Georgia |
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| Todua Clinic | Tbilisi | Georgia |
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| Centrul de Oncologie Sfantu Nectarie | Craiova | Romania |
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| Institute for Oncology and Radiology of Serbia | Belgrade | Serbia |
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| Military Medical Academy | Belgrade | Serbia |
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| Oncology Institute of Vojvodina | Kamenitz | Serbia |
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| University Clinical Center Kragujevac, Clinic for Oncology | Kragujevac | Serbia |
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| University Clinical Center Nis, Clinic for Oncology/ | Niš | Serbia |
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| Excellentis Clinical Trial Consultants | George | South Africa |
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| The Medical Oncology Center of Rosebank | Johannesburg | South Africa |
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| WITS Clinical Research - Wits Donald Gordon Medical Centre | Johannesburg | South Africa |
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| Phoenix Pharma Pty Ltd | Port Elizabeth | South Africa |
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| Hospital Universitario Vall d\'Hebron | Barcelona | Spain |
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| Instituto Oncológico Dr. Rosell (IOR) - Hospital Universitari Quirón Dexeus | Barcelona | Spain |
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| START Madrid - Hospital Universitario Fundación Jiménez Díaz | Madrid | Spain |
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| Hospital Virgen de Arrixaca | Murcia | Spain |
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| Institut d'Investigació iInnovació Parc Taulí | Sabadell | Spain |
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| Hospital Universitario Virgen del Rocío (HUVR) | Seville | Spain |
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| Hospital Universitario Virgen Macarena | Seville | Spain |
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| Universities, 1604. Cadde No 9 Ankara, Ankara 06800 Türkiye, Ankara Billkent Şehir Hastanesi | Ankara | Turkey (Türkiye) |
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| Ege University Tulay Aktas Oncology Hospital | Bornova | Turkey (Türkiye) |
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| Dokuz Eylul University Medical Oncology Hospital Dokuz Eylül Üniverstesi Medikal Onkolji Hastanesi | Konak | Turkey (Türkiye) |
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| ID | Term |
|---|---|
| D008545 | Melanoma |
| D009369 | Neoplasms |
| C563326 | Diabetes Mellitus, Insulin-Dependent, 12 |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D000077594 | Nivolumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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