Phase 1/1b study of direct intratumoral injection of pleural mesothelioma of immunostimulant prior to surgical resection.

Abstract

To evaluate the role of neoadjuvant injection of the viral mimic poly-ICLC (polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose) in patients with pleural mesothelioma undergoing curative-intent surgical resection. Patients with documented pleural mesothelioma who were deemed resectable underwent intratumoral injection of poly-ICLC 2-4 weeks prior to planned curative-intent surgery. Safety and toxicity were the primary endpoints. Secondary endpoints were postoperative complications, mortality, and overall survival (OS), with patients censored at the date of last follow-up if not known to be deceased. Between 2020 and 2024, 19 patients underwent treatment followed by pleurectomy/decortication a median of 19 days (range, 14-192 days) later. Poly-ICLC was well tolerated, with drug-related grade I toxicities occurring in 7 patients (37%). All patients were resectable and had the diaphragm and pericardium preserved. The median length of stay was 7 days (range, 3-19 days), postoperative complications were minor, except 1 cardiac arrest due to complete heart block, and there were no deaths within 90 days of surgery. The median OS was 19.6 months from injection (95% confidence interval [CI], 14.7 months to not reached [NR]) and 19.1 months from surgery (95% CI, 13.4 months to NR). One patient in whom surgery was delayed and who underwent systemic chemotherapy following injection was found to have a complete response to poly-ICLC and systemic treatment. This prospective clinical trial is the first to demonstrate the safety of intratumoral injection of poly-ICLC with excellent surgical results and favorable survival, with 1 patient experiencing a dramatic response to injection and chemotherapy. The use of poly-ICLC as an immunostimulant with combinatorial strategies offers hope for treating this challenging disease.