Predictive biomarkers for PFS in patients receiving quaratusugene ozeplasmid.

e15184 Background: Quaratusugene ozeplasmid is a gene therapy that delivers a plasmid coding for the TUSC2 tumor suppressor gene to lung cancer cells, as > 80% of lung cancers have been shown to have decreased or absent TUSC2 protein. TUSC2 protein levels have not correlated with PFS, presumably because of the complexities of TUSC2 protein regulation. Preclinical studies have identified higher levels of Trop-2 protein in organoids and lower levels of PTEN protein in lung cancer cell lines as correlating with response (AACR 2026). Tumor tissue from patients in clinical trials with quaratusugene ozeplasmid were evaluated for Trop-2 and PTEN protein expression. Methods: Monoclonal antibodies against Trop-2 (BSB148 from BioSB) and PTEN (138G6 from Cell Signaling Technology) were used for immunohistochemistry in paraffin sections from archival tumor samples in patients enrolled in 3 clinical trials with quaratusugene ozeplasmid and results expressed as H-scores. H-scores were calculated by evaluating diaminobenzidine staining intensity using the formula [1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)]. Results: Data on Trop-2 and PTEN protein expression and data on Progression Free Survival (PFS) were available from 18 patients enrolled in clinical trials with quaratusugene ozeplasmid. Six patients with NSCLC were enrolled in the Acclaim-1 trial in combination with osimertinib, and one was enrolled in the Acclaim-2 trial in combination with pembrolizumab. Eleven patients with SCLC were enrolled in the Acclaim-3 trial in combination with atezolizumab. In patients with NSCLC, Trop-2 H-scores above 100 correlated with prolonged PFS (p = 0.05), and PTEN H-scores below 100 correlated with prolonged PFS (p = 0.03). In patients with SCLC, Trop-2 H-scores were universally low, and thus non-evaluable. PTEN H-scores in patients with SCLC did not correlate with prolonged PFS (p = 0.53). Conclusions: Following up on preclinical cell line and organoid models indicating that Trop-2 and PTEN protein expression correlated with response, levels of Trop-2 and PTEN protein were evaluated in patients treated with quaratusugene ozeplasmid. Despite the small number of samples evaluated, both Trop-2 H-scores above 100 and PTEN H-scores below 100 correlated with longer PFS in patients with NSCLC, but not in patients with SCLC. Clinical trial information: NCT04486833 ; NCT05062980 ; NCT05703971 .