Quality of life in cancer patients treated with anchored interleukin-12 (IL-12) immunotherapy: Results from a first-in-human phase 1 trial of tolododekin alfa (ANK-101).

2593 Background: Anchored immunotherapy is a novel method for retaining high concentrations of anti-tumor drugs in established tumors with limited systemic exposure. The integration of quality-of-life (QOL) assessment in a phase 1 study of anchored IL-12, tolododekin alfa (ANK-101), provided an opportunity to gather baseline QOL data, longitudinally measure patient well-being during drug exposure, identify associations between adverse events and patient well-being, and generate additional clinical benefit information. Methods: All patients enrolled in the phase 1 clinical trial of ANK-101 for patients with advanced/metastatic solid tumors were eligible and provided written informed consent. Patients were treated with direct intratumoral injection every 3 weeks up to 8 cycles over 6 months. QOL was measured by the validated FACT-G survey, which collects scores across a 27-item questionnaire that measures physical, family/social, emotional, and functional well-being. Subjects were asked to complete the FACT-G at baseline every 3 weeks during treatment and at end-of-treatment. QOL scores were evaluated by paired-sample t-tests to evaluate differences in QOL at various time intervals. Data cut-off was on October 21, 2025. Results: 39 of 40 (98%) patients completed at least two FACT-G surveys. The median age was 68 and 44% were female. Patients had a median of 5 lines of prior therapy (range 1-18). The most common cancer types included were melanoma (33%), head and neck (18%), cutaneous squamous cell carcinoma (8%), and colorectal cancer (8%). There were no dose-limiting toxicities but there were 42 grade 2 events in 13 subjects and five grade 3 events in 3 subjects (elevated liver transaminases, abdominal pain, neutropenia, stomatitis). At baseline, the median of QOL score was 80.5 (range 51-106). After two and four cycles, there was no decrease in QOL scores across any of the functional domains. For patients who developed grade 2 or 3 adverse events, there was a trend toward decreased QOL in social well-being (median 25.5 at baseline to 23 after two cycles; median change -2.0; p=0.08) and in physical well-being (median 24 at baseline to 20 after four cycles; median change -5.5; p=0.06 after four cycles). Patients who completed all 8 cycles of treatment demonstrated no change in any QOL measure (p range 0.14-0.70). Conclusions: ANK-101, the first anchored immunotherapy, was associated with QOL scores that were not significantly diminished in heavily pre-treated advanced cancer patients with a non-significant decrease in social and physical well-being among those who developed grade 2 or greater adverse events. Further, patients with visceral tumors had no difference in QOL compared to superficial lesions. Early implementation of QOL data is feasible in phase 1 trials and may be of use to identify drug impact on clinical and safety measures. Clinical trial information: NCT06171750 .