Advanced (Unresectable or Metastatic) Melanoma
Conditions
Brief summary
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
Interventions
DRUGMB11 (Proposed Nivolumab Biosimilar)
During fist 12 cycles: 3 mg/kg IV infusion, over 30 minutes, Q2W. On Cycle 13 onwards: 3 mg/kg IV infusion, over 30 minutes, Q2W or 240 mg flat dose Q2W dosing
DRUGEU-Opdivo®
During fist 12 cycles: 3 mg/kg IV infusion, over 30 minutes, Q2W. On Cycle 13 onwards: 3 mg/kg IV infusion, over 30 minutes, Q2W or 240 mg flat dose Q2W dosing
DRUGUS- sourced Opdivo®
During fist 12 cycles: 3 mg/kg IV infusion, over 30 minutes, Q2W. On Cycle 13 onwards: 3 mg/kg IV infusion, over 30 minutes, Q2W or 240 mg flat dose Q2W dosing
Sponsors
mAbxience Research S.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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). 2. Body weight ≥50 kg at baseline. 3. Signed informed consent must be obtained before initiation of any study-specific procedures or treatment. 4. ECOG performance status of 0 or 1. 5. Life expectancy for at least 3 months. 6. 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
Exclusion criteria
#2. 7. At least 1 measurable disease lesion by CT or MRI per RECIST v1.1 criteria. 8. 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. 9. 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. 10. Any BRAF mutation status is allowed (BRAF-mutated, BRAF wild-type or non-mutated, or BRAF status unknown). 11. Adequate organ function (bone marrow, hepatic, renal, haematologic, endocrine, and coagulation function) should be demonstrated during the screening period. This is defined as: 1. 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. 2. Renal function: serum creatinine level ≤1.5 × ULN or calculated CrCl ≥60 mL/min (using the Cockcroft-Gault formula). 3. 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). 4. 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. 5. 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. 12. 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. 13. Non-fertile females can be included.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To demonstrate the Pharmacokinetic (PK) bioequivalence between MB11 and EU/ US-Opdivo. | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To compare the efficacy of MB11 with Opdivo based on other efficacy parameters and timepoints over the study period. | Week 1 - Week 52 | Progression-free survival (PFS) |
| .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 | Maximum concentration (Cmax), Minimum concentration (Ctrough), |
| To assess the safety and tolerability of MB11 as compared with Opdivo® | Week 1 - Week 52 | Treatment-emergent adverse events (TEAEs) |
| To assess the immunogenicity of MB11 as compared with Opdivo® | Week 1 - Week 52 | Anti-drug antibodies (ADAs) and Neutralizing antibodies (NAbs) in ADA-positive samples |
Countries
Portugal, Ukraine
Contacts
CONTACTSusana Millán, PhD
CONTACTCamino Huerga
Outcome results
None listed