Found 2 Presentations For Request "ANV419"
39P - ANV419 is a novel CD122-biased IL-2/anti-IL-2 fusion protein with potent CD8 T cell and NK cell stimulating capacity that shows additive efficacy in combination with checkpoint inhibitors and treatments acting through antibody dependent cellular cytotoxicity
- Kirsten Richter (Bottmingen, Switzerland)
Abstract
Background
ANV419 is an antibody-cytokine fusion protein with natural affinity to the heterodimeric IL-2Rβ/γ, but no affinity for IL-2Rα. Therefore, ANV419 preferentially stimulates CD8 T cells and NK cells over regulatory T cells. ANV419 is currently being investigated in a phase I/II dose finding study in patients with solid tumors. Goal of the presented study was the evaluation of the activity of ANV419 on NK cells and its potential combination with complementary immune-oncology mechanisms that can strengthen its NK or CD8 T cell anti-tumor response for the planned phase II trials.
Methods
The signaling properties and effects of ANV419 on NK cell receptor expression were compared to IL-2 and IL-15 in human PBMCs. NK cell killing was analyzed in combination with trastuzumab in vitro and in the N87 xenograft mouse model. Combination of ANV419 with checkpoint inhibitors was tested in the H22 syngeneic tumor mouse model.
Results
In NK cells, ANV419 showed STAT5 phosphorylation kinetics and NK receptor regulation that was comparable to recombinant IL-2 and IL-15. In vitro combination of ANV419 with the antibody dependent cellular cytotoxicity (ADCC) inducing anti-HER2 antibody trastuzumab showed additive effects in NK cell killing compared to single trastuzumab treatment. In line with the in vitro findings, the combination of trastuzumab and ANV419 exhibited additive effects in the N87 xenograft model supporting clinical combination of ANV419 with treatments fostering NK cell mediated killing. To assess the role of ANV419 in indications where T cells are involved in tumor resolution, ANV419 combination with the checkpoint inhibitors anti-PD1 or anti-CTLA4 was tested and showed additive effects in tumor growth retardation in mice bearing H22 tumors compared to single treated mice.
Conclusions
The data presented here, support the initiation of clinical phase II studies assessing ANV419 treatment in indications in which NK and CD8 T cells are involved in tumor resolution and in combination with ADCC inducing treatments or checkpoint inhibitors.
Legal entity responsible for the study
Anaveon AG.
Funding
Syncona, Novartis Venture Fund, Forbion, Cowen Healthcare investments, Pfizer Ventures, Pontifax, UZH Life Sciences Fund, BaseLaunch.
Disclosure
All authors have declared no conflicts of interest.
749P - ANV419, a selective IL-2R-beta-gamma targeted antibody-IL-2 fusion protein, in patients with advanced solid tumors, a phase I/II study
- Heinz Läubli (Basel, Switzerland)
Abstract
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.
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.