Dr Moser on Outcomes for WTX-124 ± Pembrolizumab in Advanced Immune-Sensitive Solid Tumors

[With] high-dose IL-2, very few patients are actually healthy enough to receive this treatment due to the [AEs]. In this study, we showed that multiple nonagenarians, so 90-year-olds, were treated, which is striking compared [with] the historical toxicity of IL-2.

Justin Moser, MD, medical director of the Melanoma and Cutaneous Oncology Program in the Oncology Research Division at HonorHealth Research Institute, discussed findings from a phase 1/1b study (NCT05479812) evaluating the tumor-activated interleukin-2 (IL-2) prodrug WTX-124 alone or in combination with pembrolizumab (Keytruda) in patients with relapsed/refractory, advanced immune-sensitive solid tumors, highlighting the agent’s safety profile and its activity in tumor types not traditionally considered responsive to IL-2. Data from the study were presented at the 2026 SITC Annual Meeting

WTX-124 is a conditionally activated IL-2 designed to remain inactive in circulation and release IL-2 selectively in the tumor microenvironment, with the goal of avoiding the systemic toxicities, including vascular leak syndrome, that have limited the use of high-dose IL-2. The open-label, multicenter dose-escalation and expansion study is evaluating intravenous WTX-124 given every 2 weeks as monotherapy and in combination with pembrolizumab.

According to Moser, the most striking aspect of the reported data was the safety profile of WTX-124. Historically, few patients have been fit enough to tolerate high-dose IL-2, he explained, whereas several patients in their 90s were treated in this study. The most common grade 3 or higher toxicities were arthralgia and decreased lymphocyte counts, Moser noted. Across all grades, the most frequent adverse effects were arthralgia, fatigue, and fever, which were manageable, he added.

Regarding efficacy, WTX-124 demonstrated activity in tumors known to be responsive to IL-2, including multiple responses in patients with cutaneous melanoma, Moser said. Notably, responses were also observed in immune-sensitive tumor types that are not typically thought to respond to IL-2, such as gastroesophageal cancer and non–small cell lung cancer, he explained.

These findings suggest that by limiting the toxicities that historically confined IL-2 therapy to a narrow group of patients, WTX-124 could extend IL-2–based treatment to older patients and a broader range of immune-sensitive tumors, Moser concluded.