Module 6

02/10/2024

Example: Keytruda (active pembrolizumab) for Cancer Maximise the potential opportunities to extend the medicinal product Pre-marketing clinical trials to support marketing authorisation: • Phase 1: open-label evaluating safety, tolerability, PK, PD and anti-tumour activity in patients with melanoma. Several parts: o Part A : dose escalation in patients with tumours. Patients enrolled sequentially at escalating doses 1, 3, 10mg/kg every 2 weeks o Part B & C with and without patients treated with ipilimumab and Part D : evaluated safety and efficacy in patients with advanced melanoma at 3 doses: 2mg/kg Q3W, 10mg/kg Q3W, 10mg/kg Q2W • Phase 2: randomised (1:1:1), double-blinded, active-control, pembrolizumab (2mg/kg Q3W and 10mg/kg Q3W) vs chemotherapy (investigator choice SOC) in patients with advanced melanoma. [interim analysis] • Phase 3: 1 single pivotal trial. Randomised controlled 3-arm, 2 doses (2mg/kg Q3W and 10mg/kg Q3W) versus active-comparator ipilimumab in patients with unresectable or metastatic melanoma. [2 x interim analysis]

Pivotal clinical trial results: • Keytruda can delay worsening of melanoma and improve survival. •

Results from a study of 540 previously treated patients with melanoma showed that 2 years after start of treatment, the disease had not worsened in 16% of patients treated with Keytruda compared with less than 1% of patients treated with chemotherapy. • Overall safety data supported the efficacy of Keytruda as monotherapy in patients naïve to ipilimumab and patients that have been previously treated with ipilimumab in melanoma patients with advanced disease.

Post-authorisation commitments: • Post-approval commitments were imposed by CHMP: completion of Phase 2 & Phase 3 studies and a biomarker study.

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Example: Adcetris (active: brentuximab vedotin) A balance of extensions to the brand and additional safety modifications to the PI

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