A Phase I/IIa First-in-Human Single-arm Open-label Multicentre Clinical Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Ascending Doses of a Cisplatin-based Formulation Administered as Dry Powder for Inhalation in Combination with First Line Standard of Care in Patients with Stage IV Non-Small Cell Lung Cancer
Administration of cisplatin by inhalation (pulmonary route) is a promising additional approach that may overcome the limitations of conventional chemotherapy and increase the efficacy of the current SoC via sustained local attack on the lung tumours of patients treated using immune checkpoint inhibitors with or without iv chemotherapy.
Use of a dry powder inhaler enables a high therapeutic response by delivering high local concentrations of a well-established active substance without the usual undesired reactions that limit the use of high doses when administered through the conventional systemic route.
Thanks to limited systemic exposure to the cytotoxic active ingredient with the use of a dry powder inhaler, such add-on treatment enables considering 5 times weekly administration of inhaled chemotherapy at the patient’s home. Increasing the frequency of local chemotherapy treatment in this way may enhance activation of the systemic anti-tumour immune response via local activation and stimulation of tumour-specific antigen release as a result of a safe, sustained and prolonged local effect, compared to the peak/short effect of iv chemotherapy.
Patients with stage IV NSCLC will be divided in two populations:
Population 1: Stage IV NSCLC patients with PD-L1 expression assessed by TPS ≥50%, hence being treated, as a first line SoC, with iv pembrolizumab.
Population 2: Stage IV NSCLC patients with a PD-L1 expression assessed by TPS <50%, hence being treated, as a first line SoC, with a combination of iv pembrolizumab and iv carboplatin-doublet chemotherapy (either pemetrexed + carboplatin in non-squamous NSCLC patients or paclitaxel + carboplatin in squamous NSCLC patients).