OP-NEU-101: A phase 1/2 open-label, dose finding and expansion study to investigate the safety and effectiveness and determine the optimal dose of N17350 administered intratumorally in participants with advanced solid tumors.

Abstract

TPS2679 Background: Despite advances in targeted therapies and immunotherapy, many patients with advanced solid tumors have limited treatment options. N17350 is a first-in-class, optimized therapeutic elastase designed for intratumoral administration that selectively induces cancer cell death by activating the neutrophil elastase (ELANE) pathway while preserving immune cell viability. Preclinical studies demonstrated broad antitumor activity across 30 cancer cell lines, 15 in vivo models, and 45 patient-derived tumor samples, as well as induction of antitumor immunity in both immunologically cold and hot tumors (Gujar et al., 2025; doi:10.1016/j.xcrm.2025.102446. Together with preclinical toxicology studies supporting a starting dose within the therapeutic range, these findings support the clinical evaluation of N17350. Methods: This first-in-human, multicenter, open-label Phase 1/2 study (OP-NEU-101) is evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of intratumorally administered N17350 in adults with advanced solid tumors. The study consists of a dose-finding and dose-optimization phase (Parts A1 and A2) followed by monotherapy expansion cohorts (Part A3). Dose-finding in participants with superficial (Part A1) and visceral lesions (Part A2) is guided by a Backfill Bayesian Optimal Interval (BF-BOIN) design to determine the maximum tolerated dose, optimal biologic dose, and/or recommended Phase 2 dose (RP2D). Once optimal dose(s) are identified, up to five tumor-specific expansion cohorts (data dependent: SCCHN, NSCLC, TNBC, cuSCC, Melanoma) may be opened to further characterize safety and clinical activity. Key Eligibility Criteria: Eligible participants are adults with advanced or metastatic solid tumors who have progressed on or are intolerant to standard therapies, have ECOG performance status 0–1, adequate organ function, and at least one superficial or visceral lesion suitable for intratumoral injection. Endpoints: The primary endpoints of the dose-finding phase are safety and tolerability, including the incidence of dose-limiting toxicities and treatment-emergent adverse events. Secondary endpoints include PK, immunogenicity, and preliminary antitumor activity assessed per RECIST v1.1 and/or itRECIST. Exploratory endpoints include evaluation of ELANE pathway activation, immune modulation, circulating tumor DNA, and multiomic analyses of tumor tissue and peripheral blood. The study has been initiated and will be enrolling participants at sites in the United States and Australia. Clinical trial information: NCT07339176 .