Drug Name (Brand / Generic)
Keytruda / pembrolizumab
Keytruda (pembrolizumab) is an anti-programmed death receptor-1 (PD-1) therapy initially indicated for the treatment of unresectable or metastatic melanoma.
Developed by Merck, the drug received approval from the US Food and Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma and progression of the disease in September 2014. It was also granted breakthrough therapy designation by the FDA.
In addition, the drug received the FDA’s approval for various indications, including advanced non-small cell lung cancer (NSCLC), hepatocellular carcinoma, microsatellite instability-high (MSI-H) cancer and Merkel cell carcinoma.
The European Commission (EC) approved the drug for the treatment of advanced NSCLC in January 2017.
Keytruda received approval from the China National Drug Administration (CNDA) for the treatment of advanced melanoma in July 2018.
The Japan Pharmaceuticals and Medical Devices Agency (PMDA) granted five approvals to Keytruda as monotherapy or in combination for the treatment of advanced NSCLC, MSI-H and melanoma in January 2019.
The drug is also approved in Canada and Australia.
A mitogen-activated protein kinase (MEK) inhibitor, indicated for treatment of unresectable or metastatic melanoma in adults.
Melanoma is a type of cancer that develops in the pigment-producing cells of the skin. It starts as a small pigmented patch on the skin. It can cause moles to become flattened, raised or irregular in shape, as well as form different coloured spots. In the metastatic stage, the disease spreads to surrounding areas and destroys tissues.
Causes of the disease include over exposure to the sun, repeated tanning with ultraviolet A (UVA), family history of melanoma and the development of other skin cancers.
Around 75,000 new cases of melanoma are recorded in the US every year. Of all the diagnosed skin cancers, Melanoma causes the highest number of deaths.
Keytruda is a humanised monoclonal antibody (mAb) that boosts the body’s immune system and enhances the ability to fight against melanoma-causing tumours.
The drug prevents the interaction between PD-1 and its ligands, including PD-L1 and PD-L2. Keytruda is available in 50mg dose single-use vials, which can be administered intravenously.
The US FDA’s approval for Keytruda was based on results obtained from a Phase Ib clinical trial named KEYNOTE-001 study. It was an open-label, multi-centred, randomised, dose-comparative study that enrolled 411 patients with unresectable or metastatic melanoma and progression of disease.
The study enrolled patients that were treated with two or more doses of ipilimumab at 3mg/kg or higher alongside a BRAF or MEK inhibitor. The study excluded patients with auto immune diseases and with a history of adverse reactions with ipilimumab. The average age of the patients that participated in the study was 61 years.
Patients were randomised to receive 2mg/kg or 10mg/kg of Keytruda every three weeks. The dose was continued until some disease progression or some toxicity was noticed.
The primary endpoint of the study was confirmed overall response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS) and duration of response. Tumour response in advanced melanoma was evaluated using response evaluation criteria in solid tumours using blinded independent central review and duration of response. The drug’s performance was observed by assessing the status of the tumour every 12 weeks.
The most common adverse reactions found in the Keytruda-administered patients included fatigue, cough, nausea, pruritus, rash, decreased appetite, arthralgia, constipation and diarrhoea.
Preliminary results of the study demonstrated that in 89 patients who received 2mg/kg of Keytruda, the overall response rate (ORR) was 24%, and the response duration ranged between 1.4 and 8.5 months.
Keytruda’s approval for NSCLC was based on the results of a Phase III clinical trial KEYNOTE-189, which demonstrated significant improvement in the OS and PFS of the patients receiving Keytruda than those on placebo.
The approval of the drug for hepatocellular carcinoma was based on the positive outcomes of the phase II clinical study KEYNOTE-224. The ORR was the primary endpoint of the study.
The FDA granted approval to Keytruda for the gastric cancer treatment on the basis of the results of phase II clinical study KEYNOTE-059.
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