Phase I, open-label study of pasireotide in patients with <i>BRAF-</i>wild type and <i>NRAS</i>-wild type, unresectable and/or metastatic melanoma.

Somatostatin analogues exert antitumour activity via direct and indirect mechanisms. The present study was designed to assess the safety and efficacy of pasireotide in patients with &lt;i&gt;BRAF&lt;/i&gt; -wild type (WT) and &lt;i&gt;NRAS&lt;/i&gt; -WT metastatic melanoma. Patients with unresectable and/or metastatic melanoma or Merkel cell carcinoma were eligible. Pasireotide was administered at different doses for ≤8 weeks in dose-escalation phase, followed by long-acting pasireotide 80 mg or lower dose in case of toxicity in follow-up phase up to six additional months. Primary endpoint was safety in the first 8 weeks of dose-escalation phase. The study was terminated early due to slow recruitment. Of the 10 patients with metastatic melanoma enrolled, only four reached the high dose level: two patients reached 3600 µg in dose-escalation and follow-up phases and two patients reached 3600 µg in dose-escalation and long-acting pasireotide 80 mg in follow-up phases and were stable for &gt;5 months. Most common adverse events (AEs) during dose-escalation phase in ≥2 patients (20%) were: diarrhoea (50%), nausea (50%), fatigue (20%), hyperglycaemia (20%), hypophosphatemia (20%), chills (20%) and tumour pain (20%). Grade 3 or 4 study drug-related AEs were diarrhoea and nausea, reported in one patient. Partial response was documented in one patient and stable disease in another. Pasireotide was well tolerated, and safety results were similar to those previously reported in other indications. Further studies are needed to evaluate its antitumour activity alone and in combination with other drugs in melanoma