Subcutaneous (Sc) Dosing Of Recombinant Human Interleukin-21 (Ril-21) Is Safe And Has Clinical Activity: Results From A Dose-Escalation Study In Stage 4 Melanoma (Mm) Or Renal Cell Cancer (Rcc)

3041 Background: IL-21 plays a key role in cancer immunology, and rIL-21 administered IV and SC is currently in clinical trials as monotherapy and in various combinations. The maximum tolerated dose (MTD) for rIL-21 administered IV (thrice weekly or repeated 5-day cycles) was previously determined to be 30–50μg/kg. Here we report the outcome of a SC dose-finding study. Methods: A phase I, open label, dose escalation, safety and tolerability study of rIL-21 administered SC in patients with stage 4 MM or RCC. Primary objective: To assess safety and tolerability of escalating doses of rIL-21 using a 3/W dosing regimen, and to determine the SC MTD. Secondary objectives: dose-response relationship for selected biomarkers, pharmacokinetics, immunogenicity and effect on tumor size per RECIST. Eligible patients had histologically confirmed melanoma or RCC and surgically incurable stage 4 disease, PS 0–1, life expectancy > 3months, and no CNS involvement. rIL-21 was administered 3/W for 8 weeks, and pts without symptomatic progression after 8 weeks were offered an additional 8 weeks of treatment. Results: A total of 23 pts were included (11 RCC, 12 MM) at the following dose levels: 3, 10, 30, 100, 200, and 300μg/kg. No dose limiting toxicity was observed at any dose level, but the trial was stopped after inclusion of 7 pts at 300μg/kg due to inconveniently high SC injection volumes at higher doses. The safety profile was similar to but milder than what was observed in phase 1 studies of rIL-21 given IV. Typical adverse events were fever, malaise, rash, all grade 2 or less. Best tumor responses include 1 CR of 6 months duration (MM with cutaneous, lung and lymph node involvement treated at 10μg/kg) and 2 confirmed PR (RCC with abdominal mass and RCC with lung and mediastinal lymph node metastases both treated with 200μg/kg). Not all pts have been evaluated for response yet. Conclusions: rIL-21 can be safely administered in a 3/W regimen in doses up to and including 300μg/kg; a true MTD was not reached with the present drug formulation of 10mg/mL. To date clinically meaningful responses including 1 CR and 2 PR were observed among 23 pts exposed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novo Nordisk Novo Nordisk Novo Nordisk