A Phase II Study of the Interleukin-6 Receptor Inhibitor Sarilumab in Combination With Ipilimumab, Nivolumab and Relatlimab in Patients With Unresectable Stage III or Stage IV Melanoma

Summary

This study will evaluate how safe the study drug is, how well patients tolerate it, how it works in the body, and the disease's response to the drug. The study drug being tested is sarilumab, when given with the combination of ipilimumab, nivolumab, and relatlimab in patients like yourself, with stage III or stage IV melanoma that cannot be removed by surgery. Previous studies have provided a strong rationale for combining sarilumab, with ipilimumab, nivolumab and relatlimab in metastatic melanoma to reduce side effects and potentially work better for your type of cancer. Sarilumab is an FDA-approved inhibitor of the receptor for the cytokine IL-6, currently approved for the treatment of rheumatoid arthritis, but it is not FDA-approved to treat melanoma. This means that the use of Sarilumab to treat melanoma is considered investigational. The other drugs which will be administered in this study, ipilimumab and nivolumab, are also monoclonal antibodies, but they target different proteins. Ipilimumab and nivolumab are both approved by the FDA to treat advanced stage III and IV melanomas. The nivolumab + relatlimab FDC (fixed dose combination) being used in this study is considered investigational, meaning it is not approved by the FDA. The combination of sarilumab, ipilimumab, nivolumab and relatlimab is considered investigational because it has not yet been approved by the FDA. The FDA has given its permission to study the investigational combination of these drugs in this research study.

Detailed description

This is a Phase II study conducted in two stages. In the first stage, up to 33 patients will be treated with all four drugs in a single arm open label trial. In the second stage, 72 patients will be randomized 1:1 to receive ipilimumab, nivolumab and relatlimab with or without sarilumab for up to 24 weeks. The study will include an assessment of the safety and tolerability and overall response rates of sarilumab administered concurrently at 150 mg flat dose every 2 weeks for 12 doses in combination with ipilimumab for three doses given every 8 weeks, and fixed dose nivolumab and relatlimab given every 4 weeks for six doses to week 24, then maintenance nivolumab and relatlimab every 4 weeks and ipilimumab every 8 weeks for up to a total of two years to patients with advanced melanoma in the first stage, and a comparison of the co-primary endpoints in the second randomized stage of the trial. Treatment will be divided into an 8-week induction and subsequent maintenance phases.

Arms & interventions

• DrugSarilumab

  Injectable solutions of sarilumab are formulated in 2 mL of aqueous solution in a 5 mL vial containing 175 mg/ml of sarilumab arginine (8.94 mg), histidine (3.71 mg), polysorbate 20 (2.28 mg), sucrose (57 mg) and Water for Injection USP.Patients will be administered sarilumab at a dose of 150 mg subcutaneously in combination with ipilimumab, nivolumab and relatlimab given intravenously, with nivolumab/relatlimab given intravenously, or sarilumab at a dose of 150 mg subcutaneously given alone.

• DrugIpilimumab Injection

  Ipilimumab injection is a sterile, nonpyrogenic, clear to slightly opalescent, colorless to pale yellow solution, single-use, preservative-free, isotonic aqueous solution that may contain particles. It is formulated at a concentration of 5 mg/mL ipilimumab in TRIS hydrochloride (also known as 2-amino-2-hydroxymethyl-1,3-propanediol hydrochloride), sodium chloride, mannitol, pentetic acid (also known as diethylenetriaminepentaacetic acid or DTPA), polysorbate 80, and water at pH 7.0. Sodium hydroxide and/or hydrochloric acid may be used to adjust the pH of the solution. Ipilimumab Injection 200 mg/40 mL (5 mg/mL) is packaged in a 50-cc Type I flint molded glass vials.

• DrugNivolumab/Relatlimab

  The FDC drug product, referred to as nivolumab/relatlimab, contains relatlimab and nivolumab in a single vial in a kit of 2 vials. The product is a sterile, non-pyrogenic, single-use, isotonic aqueous solution for IV infusion. It is formulated at a total protein concentration of 16 mg/mL (4 mg/mL relatlimab and 12 mg/mL nivolumab) and is packaged in a 20-cc glass vial in a kit of two vials. Each vial contains 80 mg of relatlimab and 240 mg of nivolumab.

Outcome measures

Eligibility criteria