1031P - ANV419, a selective IL-2Rβ/γ agonist in patients with relapsed/refractory advanced solid tumors

Background

ANV419 is a potent and selective IL-2Rβ/γ selective agonist, designed to enable the delivery of high-dose IL-2 in a safe way. ANV419 leads to preferential expansion of CD8+ T and NK cells over Treg cells. ANV419-001 is an open-label, phase 1 dose escalation study of intravenous single-agent ANV419 in patients with relapsed/refractory advanced solid tumors.

Methods

A 3+3 dose escalation design was applied. Primary objective was to evaluate the safety and tolerability of ANV419. Secondary objectives include efficacy using RECISTv1.1, characterization of pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of ANV419. The DLT observation period was two weeks. ClinicalTrials.gov Identifier: NCT04855929.

Results

At the data cutoff (22 Mar 2023), 40 pts received ANV419 at 3, 6, 12 (n=1 each), 24 (n=5), 48 (n=3), 72 (n=3), 108 (n=6), 162 (n=3), 243 (n=6) and 364 μg/kg (n=5) Q2W and at 243 μg/kg Q3W (n=6). Patients were generally heavily pretreated (1-8 lines) and 75% received immune checkpoint inhibitors. Two DLTs (CRS G3, pemphigoid G3) occurred in 2 pts at 364 μg/kg. ANV419-related AEs occurred in 97.5% of pts;. 35% ≥G3, transient, self-limiting and allowing treatment continuation. The only G4 AEs were transient lymphopenia, no G5 AEs occurred. No AEs led to treatment discontinuation. The most frequent ANV419-related AEs (≥ 10% of pts) were pyrexia, chills, vomiting, nausea, CRS, increased liver enzyme levels, fatigue, diarrhea, hypotension, myalgia, rash and thrombocytopenia, mainly G1 and G2. PK data showed half-life up to 12 hrs at RP2D. ANV419 induced a dose-dependent preferential expansion of Ki67+ CD8+ T and NK cells over Ki67+ Treg cells. Among 39 pts evaluable for tumor response, SD according to RECIST v1.1 was demonstrated in 21 pts (52.5%), prolonged PR in one pt with advanced immunotherapy-resistant NSCLC.

Conclusions

Overall, ANV419 was well-tolerated. All events were self-limiting, reversible, or manageable with standard supportive care. ANV419 at a dose of 243 μg/kg was determined as MTD and RP2D. Preliminary anti-tumor activity was observed including durable response in NSCLC. Further studies assessing the antitumor activity of ANV419 in melanoma and myeloma are ongoing.

Clinical trial identification

NCT04855929.

Editorial acknowledgement

Legal entity responsible for the study

ANAVEON AG.

Funding

ANAVEON AG.

Disclosure

E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Amunix, Anaveon, AstraZeneca, BMS, Janssen, MonTa, MSD, Nanobiotix, Nouscom, Novartis, Servier, TargImmune, T-knife, Chugai, Elevation Oncology, Ellipses Pharmacy, SyneosHealth, Genmab, Diaccurate; Financial Interests, Personal, Invited Speaker: OncoDNA, PharmaMar, Roche/Genentech; Financial Interests, Personal, Full or part-time Employment, Director, Clinical Research: HM Hospitales Group; Financial Interests, Personal, Full or part-time Employment, Medical Oncologist. Clinical Investigator. Director, Clinical Research: START Madrid - CIOCC (Centro Integral Oncológico Clara Campal); Financial Interests, Personal, Member of Board of Directors, External Independent member of Board of Directors: PharmaMar; Financial Interests, Personal, Ownership Interest: START, Oncoart Associated; Financial Interests, Personal, Steering Committee Member, Member of Data Monitoring Committee: BeiGene, Sanofi, Merus; Financial Interests, Personal, Steering Committee Member: Novartis; Non-Financial Interests, Other, Non-for-profit Foundation. President and co-founder: INTHEOS (Investigational Therapeutics in Oncological Sciences) non-for-profit Foundation; Non-Financial Interests, Advisory Role: PsiOxus; Non-Financial Interests, Other, Chair of the Independent Data Monitoring Committee: EORTC IDMC; Non-Financial Interests, Member of Board of Directors, Non-for-profit Foundation, trustee member: Non-for-profit Foundation PharmaMar; Non-Financial Interests, Advisory Role, Non-for-profit foundation: CRIS Cancer Foundation, non-for-profit ; Non-Financial Interests, Member: ASCO, ESMO, SEOM, EORTC. M. Joerger: Financial Interests, Institutional, Coordinating PI, Clinical study activity: Basilea, Bayer, BMS, Immunophotonics, MSD, Novartis, Roche; Financial Interests, Institutional, Other, Clinical study activity: DaiichySankyo; Financial Interests, Institutional, Local PI, Clinical study activity: Innomedica; Non-Financial Interests, Advisory Role: Novartis, AstraZeneca, Basilea, Bayer, BMS, Debiopharm, MSD, Roche, Sanofi. H. Läubli: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Palleon Pharmaceuticals, GlycoEra; Financial Interests, Institutional, Invited Speaker: Novartis. J.S. Lopez: Financial Interests, Personal, Advisory Board: Roche Genentech, Basilea, Ellipses Pharma, Cureteq, Pierre Faber; Financial Interests, Institutional, Research Grant: Roche Genentech, Basilea, Astex. D. Hess: Financial Interests, Personal, Stocks/Shares: Novartis, Roche, Bayer. D. König: Other, Personal, Speaker, Consultant, Advisor: AstraZeneca, Sanofi, Amgen; Other, Personal, Other, Support for attending meetings and/or travel: Amgen, Roche, Sanofi; Other, Personal, Advisory Board: MSD, AstraZeneca, Merck. E. Gasal: Financial Interests, Institutional, Officer, President & Chief Medical Officer: Innovent Biologics USA; Financial Interests, Institutional, Officer, Chief Medical Officer: Anaveon AG; Financial Interests, Institutional, Stocks/Shares: Anaveon AG. E. Garralda: Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte; Financial Interests, Personal, Invited Speaker: MSD, Lilly, Roche, Thermo Fisher, Novartis, Seagen; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: BeiGene, Janssen. All other authors have declared no conflicts of interest.