Lung Cancer Cryo-Activation as a Novel Approach to Improve Cancer Immunogenicity and Augment Immunotherapy Efficacy
Cryo-activation involves the insertion of a cryoprobe in the tumor bed with subsequent cell necrosis and tumor antigens release. Such technique has the potential to induce immune-specific reactions influencing cancer cells outside of the ablated region. The addition of cryo-activation to immune-checkpoint blockers (ICB) in the advanced NSCLC setting could represent a synergistic therapeutic avenue in order to potentiate treatment responses
• Patients must be ≥18 years of age.
• Patients must have histologically or cytologically confirmed NSCLC that is advanced/metastatic or unresectable and for which no curative therapy is available.
• Patients must present PD-L1 tumor proportion score (TPS) ≥50% in order to be eligible for first-line pembrolizumab monotherapy.
• Patients may have had prior adjuvant or neoadjuvant chemotherapy for NSCLC providing completed at least 12 months prior to relapse. Patients may not have had anti-PD-1/PD-L1 agents in the adjuvant or neoadjuvant setting.
• Patients must have an ECOG performance status 0 or 1, and a minimum life expectancy of at least 12 weeks.
• Patients must have clinically and/or radiologically documented disease with at least one lesion measurable as defined by RECIST 1.1 (excluding the lesion selected for cryo-activation). All radiology studies must be performed within 21 days prior to enrollment (within 28 days if negative). The criteria for defining measurable disease are as follows:
‣ CT scan (with slice thickness of 5 mm) lesion of ≥10 mm - longest diameter (≥15 mm for nodal lesions, measured in short axis)
⁃ Chest x-ray ≥20 mm
⁃ Physical exam (using calipers) ≥10 mm
• Primary and/or secondary lung lesions or proven metastatic lymph nodes must be accessible to flexible bronchoscopy, endobronchial ultrasound (EBUS) or endoscopic ultrasound (EUS).
• Patients must have disease amenable to biopsy and be willing and able to undergo tumor biopsies at baseline, at 4 weeks following anti-PD-1 initiation and at disease progression.