A First-in-Human Phase I/IIa clinical trial (CIS-DPI-01) was conducted to investigate the safety, tolerability, pharmacokinetics and preliminary efficacy of CIS-DPI, a cisplatin-based dry powder formulation for inhalation, in combination with the current standard of care (immunotherapy with or without intravenous chemotherapy) in patients with Stage IV non-small cell lung cancer (NSCLC). CIS-DPI was administered five times weekly (5 days on – 2 days off), primarily at the patient's home.
The CIS-DPI-01 trial has now been terminated and the resulting data analysed. The findings provided encouraging preliminary signals, supporting the continued clinical development of CIS-DPI under an adapted study design. Building on the data and experience generated during CIS-DPI-01, an optimized clinical trial protocol has been developed for the next study, CIS-DPI-11. The new trial is currently being prepared for regulatory and ethics submission in Belgium and France, with study approval expected by the end of 2026.
CIS-DPI is an innovative inhaled formulation of cisplatin, a platinum-based chemotherapy widely used in the treatment of lung cancer. By delivering cisplatin directly to the lungs, this novel route of administration is intended to reduce the systemic toxicities associated with intravenous administration, enable more frequent local treatment, and potentially induce a local anti-tumour immune response through the immunogenic properties of the product. CIS-DPI-11 will further investigate the safety and therapeutic potential of this approach, using an adapted and optimized clinical development strategy informed by the findings and experience gained from CIS-DPI-01.
CIS-DPI will be administered to 2 patients' populations (split based on their Standard of Care) through 2 different phases:
A Phase I/IIa Single-arm Open-label Multicentre Clinical Trial to Investigate the Tolerability, Safety, 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 Participants with Advanced Non-Small Cell Lung Cancer
2026-527203-13-00
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 up to 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).
