Adult Patients With Stage IIB, IIC, and Stage III Melanoma Following Complete Resection (Adjuvant Settings)
Conditions
Keywords
Pembrolizumab, Melanoma, Biosimilar, Adjuvant Therapy
Brief summary
The purpose of the study is to evaluate the pharmacokinetic (PK) equivalence of Bmab1800 as compared with reference product Keytruda® in a randomized, double-blind, two-arm, parallel comparative, multi-center study in patients with resected melanoma (Stage IIB, or Stage IIC, or Stage III) as an adjuvant treatment. This study also compares the safety and immunogenicity of Bmab1800 and Keytruda.
Detailed description
This is a randomized, double-blind, two-arm, parallel-group, multicenter Phase 1 study conducted in adult patients with Stage IIB, IIC, or Stage III melanoma following complete surgical resection. Approximately 138 patients will be randomized in 1:1 ratio to receive either Bmab1800 or Keytruda. Study treatment will be administered intravenously at a dose of 200 mg every 3 weeks till Week 21. Post which the patient will continue through Week 21, with continuation through Week 24. At Week 24, following completion of all pre dose assessments, patients who were initially randomized to the pembrolizumab arm and who are eligible to continue treatment will transition to the Bmab1800 arm and receive Bmab1800 during an open label treatment period. These patients will continue to receive Bmab1800 through Week 48 (end of treatment for the open label treatment period \[EOT OL TP\]), with end of study at Week 51 (EOS OL TP), ensuring that all patients receive pembrolizumab equivalent therapy in accordance with recommended treatment guidelines. The primary objective is to demonstrate PK equivalence based on AUC0-21 and AUC over a dosage interval at steady-state (AUCτ during Cycle 7; Week 18 to Week 21) PK parameters. Safety and immunogenicity will be evaluated through Week 24. Additional safety follow-up during an open-label treatment period through Week 51.
Interventions
BIOLOGICALBmab1800
* 200 mg Q3W, intravenous infusion, over 24 weeks * Double-blind period through Week 24; eligible patients may continue in open-label period through Week 48
BIOLOGICALUS-Licensed Keytruda
* 200 mg Q3W, intravenous infusion, over 24 weeks * Double-blind period through Week 24
Sponsors
Biocon Biologics UK PLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double (Participant, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients aged ≥18 years (or legal adult age per local regulations) * ECOG Performance Status of 0 or 1 at screening and prior to randomization. * Histologically confirmed melanoma that is completely surgically resected with negative margins (per local standard), classified as: Stage IIB, IIC, or Stage III melanoma per AJCC Cancer Staging Manual, 8th edition. * Patients must have undergone definitive melanoma resection ≥28 days prior to signing informed consent, and randomization must occur within 12 weeks after surgery. * All patients must have disease-free status (ie, no evidence of locoregional recurrence or distant metastasis); no clinical evidence of brain metastases.
Exclusion criteria
* History of ocular/uveal and mucosal melanoma. * Active autoimmune disease that has necessitated chronic systemic treatment within 2 years before the first study treatment * Active, known, or suspected autoimmune disease that has required systemic treatment in past 2 years. * Prior malignancy active within the previous 3 years, except for early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy. * Prior therapy with anti-PD-1 (including pembrolizumab), anti PD-L1, anti PD L2, anti CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody) or agents that target interleukin-2 (IL-2) pathway any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways. * Requirement for systemic treatment corticosteroids (\>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of 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. * History of ocular/uveal and mucosal melanoma. * Active autoimmune disease that has necessitated chronic systemic treatment within 2 years before the first study treatment * Active, known, or suspected autoimmune disease that has required systemic treatment in past 2 years. * Prior malignancy active within the previous 3 years, except for early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy. * Prior therapy with anti-PD-1 (including pembrolizumab), anti PD-L1, anti PD L2, anti CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody) or agents that target interleukin-2 (IL-2) pathway any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways. * Requirement for systemic treatment corticosteroids (\>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of 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. * Receipt of treatment directed against the resected melanoma (eg, chemotherapy, targeted agents, biotherapy, or limb perfusion) administered after the complete resection. * History of allergy or hypersensitivity to pembrolizumab or its excipients. * History of severe hypersensitivity reaction (Grade ≥3) to any monoclonal antibody. * Received prior anticancer therapy including mAb, chemotherapy, or an investigational agent or device within 5 half-lives before first dose of study intervention or not recovered (ie, \> Grade 1 or at baseline) from AEs due to previously administered agents at screening and before randomization. * Patients with ≤ Grade 2 neuropathy are an exception and may qualify for the study. * Received a live vaccine within 30 days prior to the first dose of study intervention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Curve from Time 0 to 21 Days (AUC₀-₂₁days) | Week 0 to Week 3 | Assessed to compare pharmacokinetics of Bmab1800 and Keytruda® |
| Time Curve Over the Dosing Interval at Steady State (AUCτ) | Assessed to demonstrate steady-state PK equivalence | Cycle 7 (Week 18 to Week 21) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | From first dose through Week 24 (DB-TP) | — |
| tmax | From first dose through Week 24 (DB-TP) | — |
| Cmax,ss | From first dose through Week 24 (DB-TP) | — |
| tmax,ss | From first dose through Week 24 (DB-TP) | — |
| Ctrough | From first dose through Week 24 (DB-TP) | — |
| Incidence and severity of adverse events and serious adverse events | From first dose through Week 24 (DB-TP) | Assessed by incidence and severity of adverse events and serious adverse events |
| Immunogenicity | From first dose through Week 24 (DB-TP) | Assessed by incidence of anti-drug antibodies |
Outcome results
None listed