YERVOY

What it is

YERVOY (ipilimumab) is a recombinant, fully human monoclonal antibody that binds to the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). YERVOY is a sterile, preservative-free liquid for intravenous administration.

Approved indications

— Unresectable or metastatic melanoma (as monotherapy). — Unresectable or metastatic melanoma (in combination with nivolumab). — Intermediate or poor-risk, previously untreated advanced renal cell carcinoma (in combination with nivolumab). — Metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumour aberrations, for first-line treatment with nivolumab and platinum-doublet chemotherapy. — Unresectable malignant pleural mesothelioma, for first-line treatment in combination with nivolumab. — Unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥1%, for first-line treatment in combination with nivolumab. — Unresectable or metastatic colorectal cancer that is microsatellite instability high or mismatch repair deficient, in combination with nivolumab. — Unresectable or metastatic hepatocellular carcinoma, for first-line treatment in combination with nivolumab.

Dosing overview

For unresectable or metastatic melanoma as monotherapy, the recommended dose of YERVOY is 3 mg/kg administered intravenously over 30 minutes every 3 weeks for a total of 4 doses. For combination therapy with nivolumab, dosing varies by indication. In melanoma, the recommended dose of nivolumab in the combination phase is 1 mg/kg intravenously over 30 minutes every 3 weeks for the first 4 doses in combination with YERVOY 3 mg/kg. In renal cell carcinoma, the recommended dose is 3 mg/kg nivolumab intravenously over 30 minutes every 3 weeks for the first 4 doses in combination with 1 mg/kg YERVOY. In non-small cell lung cancer, the recommended dose is 360 mg nivolumab every 3 weeks in combination with 1 mg/kg YERVOY every 6 weeks, and platinum chemotherapy every 3 weeks. In oesophageal squamous cell carcinoma, the recommended dose is 1 mg/kg YERVOY every 6 weeks in combination with either 3 mg/kg nivolumab every 2 weeks or 360 mg nivolumab every 3 weeks.

Key safety warnings

YERVOY can cause severe and life-threatening immune-related adverse reactions that can involve any organ system. The majority of these initially manifest during treatment; however, a minority can occur weeks to months after discontinuation, and some immune-related adverse reactions can be permanent such as thyroid dysfunction and diabetes mellitus. Life-threatening or fatal immune-related adverse reactions that have occurred with YERVOY monotherapy or YERVOY and nivolumab combination therapy include colitis, intestinal perforation, hepatitis, pneumonitis, hypophysitis, adrenal insufficiency, toxic epidermal necrolysis, myocarditis, encephalitis, myasthenia gravis and neuropathy. YERVOY is associated with serious immune-related gastrointestinal reactions, and fatalities due to gastrointestinal perforation have been reported in clinical trials. YERVOY is associated with serious immune-related hepatitis, and fatal hepatic failure has been reported in clinical trials. YERVOY is associated with serious skin adverse reactions that may be immune-related, and Stevens Johnson Syndrome or fatal toxic epidermal necrolysis have been reported in clinical trials. Immune-related adverse reactions are seen more frequently, and are more severe, with YERVOY and nivolumab combination therapy than with YERVOY or nivolumab monotherapy.

Contraindications

Hypersensitivity to the active substance or to any of the excipients.

PBS listing

YERVOY injection concentrate for intravenous infusion 200 mg in 40 mL is listed on the PBS with streamlined restriction, with an ex-manufacturer price of A$21,378.52.

Regulatory history

YERVOY ipilimumab 50 mg in 10 mL and 200 mg in 40 mL concentrate solutions for intravenous infusion were first listed on the ARTG on 4 July 2011. The TGA approved YERVOY as monotherapy for the treatment of patients with unresectable or metastatic melanoma who have failed or are intolerant to prior therapy on 27 June 2011. YERVOY was evaluated as a new biological entity and first-in-class monoclonal antibody targeting CTLA-4. The PBAC recommended an amendment to the PBS listing in November 2014 to allow treatment of patients with unresectable or metastatic melanoma who have progressed on or after prior treatment with a BRAF inhibitor. In July 2016, the PBAC recommended a further amendment to the PBS restriction, specifying that treatment must be the sole PBS-subsidised therapy for melanoma, maintaining streamlined Authority Required status.