Padeliporfin VTP Using Robotic Assisted Bronchoscopy in Peripheral Lung Cancer

A multicenter, open label, phase 1/1b, safety, feasibility, and light dose titration study followed by further study of therapeutic ablation effects.

Patients with high risk of peripheral primary lung cancer, stage 1A1/1A2, for whom surgical treatment is planned, will be recruited. Patients who are candidates for lung resection will be recruited as a diagnose and treat in the same anaesthesia, protocol; surgery will be performed at least 5 days and up to 21 days following the VTP procedure.

Study intervention will consist of robotic assisted bronchoscopic Padeliporfin VTP lung ablation: vascular targeted photodynamic therapy using Padeliporfin photosensitizer, an ablation mechanism with efficacy related to immune response post-ablation.

Inclusion criteria

• Age ≥18
• Patients with primary lung lesions who are at high risk for primary lung cancer.

2.1.Biopsy with intraoperative confirmation of malignancy using on-site cytology will be used as final inclusion prior to study treatment.

• All patients will be approved by a multi-disciplinary team (thoracic surgery, interventional pulmonology, medical oncology and radiation oncology) as appropriate for bronchoscopic VTP prior to surgical resection.
• Tumor size targeted for VTP treatment ≤ 2 cm (Part A) and <3cm (Part B), based on CT scan, including solid or semi-solid tumors.
• EBUS mediastinal staging performed intraoperative prior to VTP treatment with rapid on-site evaluation negative for nodal involvement of malignancy.
• Tumor is ≥ 2cm from the central bronchial tree (distal 2 cm of the trachea, carina, and named major lobar bronchi up to their first bifurcation) (Timmerman, 2018).
• Lung lesion is not contiguous with and ≥ 1 cm from the pleura/fissures.
• Patient is eligible to undergo bronchoscopy under general anesthesia.
• Tumor is accessible for Padeliporfin VTP treatment via robotic bronchoscopy
• ECOG performance score 0-2
• Estimated life expectancy of ≥3 months
• Adequate organ system function
• Negative serum pregnancy test

Exclusion criteria

• Patient has a centrally located lung lesion, as defined by RTOG within 2 cm of the proximal bronchial tree, or within 2 cm of other major mediastinal structure (aorta, heart, trachea, pericardium, superior vena cava, pulmonary artery, esophagus, vertebra's body or spinal canal).
• Patient has a lung lesion located less than 1 cm from the pleura or fissure
• Patient has a lung cancer lesion >2cm in diameter, for the expansion cohort lesion >2-3 cm
• Patient has cytologic or histologic evidence of nodal disease
• Tumor invades major vessels
• Prior exposure to VTP or PDT treatments
• Pregnant or breastfeeding women
• Receiving any other investigational treatment
• Co-morbidities:

• Baseline hypoxia with O2 saturation <92% on 2L NC or more of oxygen
• New York Heart Association (NYHA) stage III/IV heart failure
• Unstable coronary artery disease or MI within the last 6 months
• Uncontrollable clinically serious arrhythmia
• Decompensated/clinically worsening interstitial lung disease or obstructive lung disease.
• Unstable cerebrovascular or peripheral vascular disease
• Inability to stop anticoagulation or anti-platelet therapy peri-procedure
• Evidence of clinically active infection requiring systemic (any route) antibiotic therapy. All prior infections must have resolved following optimal therapy.
• Patient has any acute or chronic condition assessed as clinically significant by Investigator which may preclude bronchoscopy procedure
• History of medical or psychiatric disease which, in the view of the investigator, would preclude safe treatment or acceptable study compliance
• Known severe pulmonary hypertension (mean pulmonary arterial pressure ≥ 50 mmHg)
• Patient has a cancer diagnosis with active disease requiring further cancer therapy.
• Patient has had major surgery within the last 4 weeks.
• Patient has porphyria or hypersensitivity to padeliporfin or porphyrin-like compounds or to any of its excipients.