A PK Study to Compare GME751 (Proposed Pembrolizumab Biosimilar) and US-licensed and EU-authorized Keytruda® in Participants With Stage II and III Melanoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the pharmacokinetic (PK) similarity and efficacy, safety, and immunogenicity of GME751 compared with Keytruda® (pembrolizumab) in subjects with resected advanced melanoma requiring adjuvant treatment with pembrolizumab.

Detailed Description
-----------------
Eligible subjects will be randomized in a 1:1:1 ratio to receive either GME751, Food and Drug Administration (FDA)-licensed pembrolizumab (Keytruda-US) or European Union (EU)-authorized pembrolizumab (Keytruda-EU). The maximum study duration for a participant will be approximately 28 weeks including screening. Treatment duration is 24 weeks (4 treatment cycles, each of 6 weeks duration). However, subject should discontinue study participation in case of disease recurrence, unacceptable toxicity or other reasons. Participants who are benefiting from treatment with pembrolizumab without signs of recurrence or unacceptable toxicity will be eligible for continued pembrolizumab treatment via most suitable option based on the respective country regulations.

Official Title
-----------------
A Randomized, Double-blind, Parallel-group Study to Compare Pharmacokinetics of GME751 (Proposed Pembrolizumab Biosimilar) and US-licensed and EU Authorized Keytruda® in Participants With Stage II and III Melanoma Requiring Adjuvant Treatment With Pembrolizumab

Conditions
-----------------
Melanoma

Intervention / Treatment
-----------------
* Drug: GME751
* Drug: Keytruda - EU
* Drug: Keytruda - US


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: At least 18 years of age Advanced Melanoma Completely removed melanoma by surgery performed within 13 weeks of randomization Adequate organ function Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Exclusion Criteria: Known history or evidence of ocular or uveal melanoma Known history of hypersensitivity (grade ≥3) to pembrolizumab or its excipients Known History of auto-immune disease Received live vaccine ≤30 days before the first study treatment Prior treatment with anti-PD-1 agents or agent against another stimulatory or co-inhibitory T cell receptor Active autoimmune disease that has necessitated chronic systemic treatment within 2 years before the first study treatment Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GME751<br>Subjects will receive GME751 via intravenous (IV) infusion. | Drug: GME751<br>* 400 mg Q6W, i.v. infusion, over 24 weeks period<br>|
| Active Comparator: Keytruda - EU<br>Subjects will receive Keytruda-EU via intravenous (IV) infusion. | Drug: Keytruda - EU<br>* 400 mg Q6W, i.v. infusion, over 24 weeks period<br>|
| Active Comparator: Keytruda - US<br>Subjects will receive Keytruda-US via intravenous (IV) infusion. | Drug: Keytruda - US<br>* 400 mg Q6W, i.v. infusion, over 24 weeks period<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Serum Concentration-time Curve from Time Zero to 42 Days (AUC0-42d) | The PK similarity (AUC0-42d) of GME751 compared with pembrolizumab will be demonstrated in subjects with advanced melanoma in the adjuvant setting. | Day 1 (Postdose) through Day 42 | 
| Area Under the Serum Concentration-time Curve Over the Dosing Interval at Steady State | The PK similarity (AUCtau_ss) of GME751 compared with pembrolizumab will be demonstrated in subjects with advanced melanoma in the adjuvant setting. | Week 19 through Week 24 |