Abstract 749P
Background
Although therapy with interleukin-2 (IL-2) can improve outcome in cancer patients, its use has been limited by significant side effects. ANV419 is a fusion protein of a highly specific anti-IL-2 antibody and human-IL-2. ANV419 is currently being investigated in the phase I/II dose finding study in patients with solid tumors (ANV419-001). The primary objective is to describe the safety and tolerability of ANV419 and RP2D.
Methods
ANV419 is administered intravenously over 15 minutes every 2 weeks, without premedication. 19 patients with (cutaneous (n=3) and non-cutaneous (n=5)) melanoma, RCC (n=3), NSCLC (n=2), CRC (n=2), HCC (n=1), pancreatic adenocarcinoma (n=1), esophageal adenocarcinoma (n=1), adenoid cystic carcinoma (n=1) have been dosed in 8 cohorts. Patients received 3, 6, 12 (n=1 each), 24 (n=4), 48 (n=3), 72 (n=3), 108 (n=3) and 162 (n=3) μg/kg of ANV419.
Results
ANV419 is generally well tolerated, all drug-related AEs are G1 or G2, no DLTs observed and MTD not reached. Most patients (63%) experienced chills (G1), with or without low-grade fever (G1) 2-4 hours post-infusion, which resolved with antipyretic treatment. Seven CRS (five G1 and two G2) events were reported of whom 2 required in house observation and were reported as SAEs. Two patients were given a single dose of dexamethasone, one with CRS and one with prolonged G2 fever. One drug related SAE of fever (G2) was reported and resolved with anti-pyretic medication. Pharmacokinetic data suggest a dose proportional increase of the ANV419 plasma concentration. Pharmacodynamic evaluation on day 4 post-dosing showed a dose dependent increase of %Ki67+ CD8 T and NK cells, but with a dose independent increase of %Ki67+ Tregs. 4 patients continue to receive ANV419. Of the 18 patients who received at least two cycles of ANV419, seven showed stable disease as per RECISTv1.1. 6 eventually progressed after 6, 7, 8, 16, 19 and 24 weeks.
Conclusions
ANV419 shows a favorable and consistent safety profile across doses and selectively induces expansion and proliferation of CD8 T and NK cells, but not Tregs. Updated clinical data including additional dose cohorts, long term PK/PD and histology will be shared at the meeting.
Clinical trial identification
NCT04855929.
Editorial acknowledgement
Legal entity responsible for the study
Anaveon AG.
Funding
Anaveon AG.
Disclosure
H. Läubli: Other, Personal and Institutional, Advisory Board: Lilly, Roche, Bristol Myers Squibb, MSD Oncology, AstraZeneca, Pfizer, Merck Serono, Boehringer Ingelheim, Eisai, Astellas Pharma, Novartis, Bayer; Other, Personal and Institutional, Speaker’s Bureau: Anaveon AG, GlycoEra, Palleon Pharmaceuticals, Bristol Myers Squibb, AstraZeneca. M. Joerger: Financial Interests, Institutional, Invited Speaker, Clinical study activity: Basilea, Bayer, BMS, Immunophotonics, Innomedica, MSD, Novartis, Roche; Financial Interests, Institutional, Other, Clinical study activity: DaiichySankyo; Non-Financial Interests, Advisory Role: Novartis, AstraZeneca, Basilea, Bayer, BMS, Debiopharm, MSD, Roche, Sanofi. E. Garralda: Financial Interests, Personal, Advisory Board: Genentech, F.Hoffmann/La Roche, Neomed Therapeutics1 Inc, Boehringer Ingelheim, Janssen Global Services, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Lilly, Hengrui; Financial Interests, Personal, Invited Speaker: Ellipses Pharma, Seattle Genetics, Bristol Myers Squibb, MSD, F-Star Therapeutics; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho. All other authors have declared no conflicts of interest.