Safety and efficacy results from a first-in-human, phase 1/2 study of ASKG915, an anti-PD-1/pro-IL-15 bifunctional fusion protein, for patients with advanced solid tumors.

Abstract

2607 Background: ASKG915 is a bifunctional fusion protein of PD-1 antibody fused with an IL-15 prodrug. Preclinical studies demonstrated the efficacy of ASKG915 in neoplastic models. Here, we present updated safety and efficacy results from a first-in-human, dose escalation and dose expansion of ASKG915 monotherapy in patients (pts) with advanced solid tumors. Methods: This open-label, multicenter, Phase 1/2 study in adult pts with advanced unresectable or metastatic solid tumors (NCT05867420) comprised two parts: dose escalation (Part 1) and dose expansion (Part 2). Pts with advanced solid tumors that were resistant/refractory to current standard treatment, and with at least 1 measurable lesion per RECIST 1.1, were eligible. The primary objective was safety. Secondary objectives included efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity. Results: As of December 30, 2025, we have treated 104 pts at dose-escalation phase (n=19) and dose expansion phase (n=85). Primary tumor types included NSCLC (n=48, 46.2%), CRC (n=35, 33.6%), ovarian cancer (n=11, 10.6%), cervical cancer (n=4, 3.8%) and others (n=6, 5.8%). Most pts (83/104, 79.8%) had received two and more lines of prior treatment, and 71 pts (68.3%) had undergone previous immunotherapy. No dose-limiting toxicities was observed in dose escalation phase, and the maximum tolerated dose has not been reached up to 3 mg/kg. In SS set, any-grade treatment-related adverse events (TRAEs) were reported in 98/104 (94.2%) pts, with the most common being rash (39/104, 37.5%), anemia (37/104, 35.6%), and elevated aspartate aminotransferase (19/104, 18.3%). ASKG915 monotherapy exhibited dose-dependent efficacy across dose levels. In the EFR cohort, encouraging antitumor activity was observed at the mid-dose level or above in both late-line NSCLC that had progressed on prior immunotherapy and MSS CRC: a 30% confirmed partial response (PR) rate (3/10) in non-liver metastatic MSS CRC at the mid-dose level or above, and a 30% PR rate (3/10) in NSCLC patients at the high-dose level. Further efficacy data will be presented at the time of the conference. CD8+ T and NK cells demonstrated proliferative expansion at mid-to-high doses. Drug plasma exposure increased dose-dependently with low activated ASKG915 levels and no ADA impact after repeat dosing. Conclusions: ASKG915 demonstrated a promising clinical efficacy in pts with MSS CRC and NSCLC, with a well-tolerated safety profile. These results support further evaluation of ASKG915 as a monotherapy and in combination therapies. Clinical trial information: NCT05867420 .