NCT07221734招募中3 期
Randomised, Multicentre, Multinational, Double-Blind Integrated Study to Compare the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of MB11 (Proposed Nivolumab Biosimilar) Versus EU-/US-Opdivo® in Subjects With Previously Untreated Advanced (Unresectable or Metastatic) Melanoma (LEON Study)
mAbxience Research S.L.15 个研究点 分布在 1 个国家目标入组 632 人开始时间: 2025年12月29日最近更新:
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 632
- 试验地点
- 15
- 主要终点
- To demonstrate the Pharmacokinetic (PK) bioequivalence between MB11 and EU/ US-Opdivo.
研究概览
简要总结
This is a randomised, multicentre, multinational, double-blind, integrated study to sompare the pharmacokinetics, efficacy, safety, and immunogenicity of MB11 versus Opdivo® in subjects with previously untreated advanced (unresectable or Metastatic) Melanoma
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years at the time of signing the informed consent (or adulthood where the legalage of majority in the country is established >18 years).
- •Body weight ≥50 kg at baseline.
- •Signed informed consent must be obtained before initiation of any study-specific procedures or treatment.
- •ECOG performance status of 0 or
- •Life expectancy for at least 3 months.
- •Untreated, histologically confirmed advanced unresectable Stage III or Stage IV melanoma, as per AJCC 8th Edition staging system. Prior melanoma systemic therapy for earlier stages is allowed for patients who have been disease-free for at least 1 year after end of therapy, except if therapy included use of prohibited medications. Prior use of immune therapies (adjuvant or neoadjuvant) is not allowed as per
排除标准
- •At least 1 measurable disease lesion by CT or MRI per RECIST v1.1 criteria.
- •Tumour tissue from an unresectable or metastatic site of disease, collected within 90 days prior to randomisation, must be available and provided for PD-L1 testing. All samples must be classified as PD-L1 positive (≥1% to <5% or ≥5%). If only the old sample >90 days is available and there is no possibility of having a new biopsy sample, then the subject will be excluded.
- •In the case of prior palliative radiotherapy (on metastatic lesions), this must have been completed at least 2 weeks prior to the study drug administration. No adjuvant radiation therapies are allowed.
- •Any BRAF mutation status is allowed (BRAF-mutated, BRAF wild-type or non-mutated, or BRAF status unknown).
- •Adequate organ function (bone marrow, hepatic, renal, haematologic, endocrine, and coagulation function) should be demonstrated during the screening period. This is defined as:
- •Haematologic function: absolute neutrophil count ≥1.5 × 109/L, platelets 9≥100 × 10 /L, and haemoglobin ≥9 g/dL.
- •** Subjects should not have received RBC transfusion prior to 14 days beforescreening labs.
- •Renal function: serum creatinine level ≤1.5 × ULN or calculated CrCl ≥60 mL/min (using the Cockcroft-Gault formula).
- •Liver function: total bilirubin level ≤1.5 × ULN (except subjects with Gilbert Syndrome, who can have total bilirubin <3.0 mg/dL), albumin level ≥LLN, AST/ALT ≤2.5 × ULN (≤5 × ULN for subjects with liver metastases).
- •Endocrine function: TSH within normal limits. If TSH is not within normal limits, the subject may still be eligible if T3 and free T4 are within normal limits.
- •Coagulation: INR and aPTT ≤1.5 × ULN unless the subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy must be on a stable anticoagulation regimen and have an INR not above the target therapeutic range for the 14 days preceding the start of the study drug.
- •Female subjects of childbearing potential and their partners, as well as male subjects with female partners of childbearing potential and their partners, must agree to adhere to the use of a highly effective method of contraception during the study and for at least 5 months after the last dose of nivolumab. Refer to Appendix 15.1 for contraception guidance.
- •Non-fertile females can be included.
- •Exclusion Criteria:
- •Subjects receiving any prior systemic therapy for advanced, unresectable, or metastatic Stage III or Stage IV melanoma (except for palliative radiotherapy, in accordance with Inclusion Criteria #9).
- •Subjects receiving any prior immunotherapy (regardless of the melanoma stage), such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-LAG or anti-CTLA-4 therapy (including ipilimumab or any other antibody or drug that specifically targets costimulation of T-cells or immune checkpoints) and/or BRAF-targeted therapy.
- •Participation in another clinical study or treatment with another investigational agent within 4 weeks or 5 elimination half-lives prior to randomisation (whichever is longer)
- •Brain metastases or leptomeningeal metastases. A negative brain imaging of less than 90 days prior to screening is required.
- •Peritoneal melanomatosis.
- •Ocular melanoma, mucosal melanoma and acral lentiginous melanoma.
- •History of another malignancy or a concurrent malignancy. Exceptions include subjects who have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ.
- •Active autoimmune disease that has required systemic treatment in the last 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin or physiological corticosteroid replacement therapy for pituitary or adrenal insufficiency [daily prednisone at a dose of ≤10 mg or equivalent]) is not considered a form of systemic treatment.
- •Subjects with hyperthyroidism or hypothyroidism are excluded but those subjects who are stable on hormone replacement will be allowed.
- •Any diagnosis of immunodeficiency, systemic steroid therapy (replacement therapy outlined in Exclusion Criteria #8, inhaled, intranasal, intraocular, or topical steroids are allowed) or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study drug.
- •Any major surgery (eg, hip or spine surgery) less than 28 days prior to the first dose of the study drug.
- •Having received a solid organ/tissue allogeneic or haematopoietic transplant.
- •History and/or current interstitial lung disease or pneumonitis (non-infectious) requiring oral or IV steroids or another immunosuppressive drug.
- •Any active or previous infection requiring therapy (oral or systemic) within 30 days prior to the first dose of the study drug.
- •Have received or are about to receive a live virus vaccination within 30 days prior to the first dose of the study drug. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
- •Known active TB or untreated latent TB.
- •Positive serology for human immunodeficiency virus (HIV 1/2), hepatitis B (HBsAg positive and/or HBcAb positive, and HBV DNA positive, refer to Section 8.3.2.1) or hepatitis C (HCVAb positive and HCV RNA positive). In addition, subjects with untreated positive serology for Strongyloides spp will be excluded.
- •At the time of signing the informed consent, the subject is a regular user (including "recreational use") of any illicit drug or have a recent history (within the past year) of substance abuse (including alcohol).
- •Be pregnant or lactating or expecting to conceive during the study or up to 5 months after the last dose of the study drug.
- •Immediate family member who is at the research site or sponsoring staff who is directlyninvolved in this study.
- •Inability to comply with protocol procedures and/or any other acute or chronic medical condition that may increase the risk for the subject associated with study participation or study drug administration, that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
研究组 & 干预措施
MB11 (Proposed Nivolumab Biosimilar)
Experimental
干预措施: MB11 (Proposed Nivolumab Biosimilar) (Drug)
EU-Opdivo®
Active Comparator
干预措施: EU-Opdivo® (Drug)
US- sourced Opdivo®
Active Comparator
干预措施: US- sourced Opdivo® (Drug)
结局指标
主要结局
To demonstrate the Pharmacokinetic (PK) bioequivalence between MB11 and EU/ US-Opdivo.
时间窗: Week 1 - Week 24
Area under the concentration-time curve (AUC) between Cycle 1 and Cycle 2 (AUC from time 0 to 504 hours postdose \[AUC0-336\]. AUC at steady state (AUCss) between Cycle 8 and Cycle 9.
To demonstrate the efficacy equivalence of MB11 and Opdivo® administered as first-line treatment in adult subjects with untreated, unresectable, or metastatic Stage III or Stage IV melanoma
时间窗: Week 1 - Week 24
Best Overall Response (BOR), prior to permanent treatment discontinuation, prior to use of other anti-cancer therapies and by 24 weeks after Day 1
次要结局
- .To compare the PK profile based on other PK parameters and timepoints (not covered by the primary PK endpoints) of MB11 as compared with Opdivo® over the study period.(Week 1 - Week 52)
- To assess the safety and tolerability of MB11 as compared with Opdivo®(Week 1 - Week 52)
- To assess the immunogenicity of MB11 as compared with Opdivo®(Week 1 - Week 52)
- To compare the efficacy of MB11 with Opdivo based on other efficacy parameters and timepoints over the study period.(Week 1 - Week 52)
研究者
研究点 (15)
Loading locations...
相似试验
已完成
不适用
A clinical trial to study the effects of two Anti-CD20 monoclonal antibodies in combination with CHOP in patients with diffuse large B-cell Lymphoma.CTRI/2012/11/003129Dr Reddys Laboratories Ltd190
已完成
3 期
A Study to Compare Efficacy, PK, PD, Safety and IMM of MB09 to Prolia® [EU-sourced] in Postmenopausal Osteoporosis.Postmenopausal Women With OsteoporosisNCT05338086mAbxience Research S.L.558
招募中
3 期
Double-blind Study to Evaluate the PK, Efficacy, Safety and Immunogenicity of MB12 Versus Keytruda® in Stage IV NSCLCNon Small Cell Lung Cancer MetastaticNCT05668650Laboratorio Elea Phoenix S.A.174
已完成
2 期
A Study of Plazomicin Compared With Levofloxacin for the Treatment of Complicated Urinary Tract Infection (cUTI) and Acute Pyelonephritis (AP)Acute PyelonephritisComplicated Urinary Tract InfectionNCT01096849Achaogen, Inc.145
已完成
3 期
An Efficacy and Safety Study of Subcutaneous Tocilizumab in Combination With Methotrexate (MTX) and as Monotherapy Versus MTX in Participants With Moderate to Severe Rheumatoid Arthritis With Inadequate Response to Current Disease-Modifying Antirheumatic Drug (DMARD) TherapyRheumatoid ArthritisNCT03155347Hoffmann-La Roche340