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631 Phase I dose escalation study in patients with advanced solid tumors with ANV419, a novel fusion protein selective for IL-2Rβ/γ
  1. Christoph Bucher1,
  2. Guzman Alonso2,
  3. Juanita Lopez3,
  4. Emiliano Calvo4,
  5. Markus Joerger5,
  6. Vicky Sanchez Perez3,
  7. Elena Corral4,
  8. Daniela Di Blasi1,
  9. Kirsten Richter1,
  10. Christoph Huber1,
  11. Julie Mouton1,
  12. Silvio Costanzo1,
  13. Sangeeta Jethwa1,
  14. Elena Gerralda2 and
  15. Heinz Läubli6
  1. 1Anaveon AG, Basel, Switzerland
  2. 2Vall d’Hebron, Barcelona, Spain
  3. 3Royal Marsden, London, UK
  4. 4START Madrid-CIOCC, Madrid, Spain
  5. 5Kantonsspital St. Gallen, St. Gallen, Switzerland
  6. 6University Hospital, Basel, Switzerland


Background ANV419 is a fusion protein of an anti-IL-2 antibody and human-IL-2 with selective signaling through IL-2Rβ/γ thus limiting the side effects of activating the IL-2Rα/β/γ ANV419 is investigated in a phase I dose finding study in patients with advanced solid tumors (ANV419-001).

Methods The primary objective of ANV419-001 is safety and tolerability of ANV419. Secondary objectives include response rate (RECISTv1.1), pharmacokinetic and pharmacodynamic evaluation. ANV419 is administered as a 15 minutes intravenous infusion Q2W. As of 29th June 2022, 26 patients with Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 and a range of primary tumor types with multiple previous lines of therapy have been enrolled and dosed in 9 cohorts up to 243μg/kg.

Results ANV419 was generally well tolerated across multiple cycles, with no dose-limiting toxicities (DLTs) up to and including 243µg/kg. The most frequent ANV419 related adverse events (AEs), reported in at least 10% of patients, were chills, fever, fatigue, nausea, vomiting, cytokine release syndrome (CRS) and increased liver function tests, mainly Grade 1 and Grade 2. All drug related events were responsive to supportive care therapy and reversible.

A dose proportional increase in ANV419 plasma concentration results in an increased estimated half-life up to 28 hours at higher doses.

In this study, IL-6, IL-8, TNF-α, and IFN-γ levels (10-Plex Panel) were transiently increased at high doses (108 and 243µg/kg), 4 hours after infusion.

Pharmacodynamic evaluation of ANV419 on day 4 post-dosing (cycle 1 and 2) showed a selective and dose dependent proliferation of CD8+ T and NK cells, with a lower increase of proliferating Tregs. As typical for IL-2 related lymphocyte sequestration, a transient dose dependent lymphopenia was observed in all patients lasting up to at least 72 hours after ANV419 infusion, followed by a dose dependent increasing lymphocyte counts up to 5.4-fold of baseline. Lymphocyte numbers keep increasing over multiple cycles up to 3.8-fold after 2 cycles (243µg/kg). In 21 patients with at least one post-baseline tumor response assessment, 52% of patients (n=11) achieved a response of SD or PR, with 10 SD, 1 PR and 10 PD.

Conclusions ANV419 maintains a favorable safety profile, while inducing a systemic inflammatory response in cancer patients with preferential proliferation of effector cells compared to high dose of IL-2. Dose escalation is ongoing. The preliminary efficacy data shows a potential for ANV419 as therapeutic option for patients with progressing/relapsing cancer. Updated data will be shared at the meeting.

Trial Registration NCT04855929

Ethics Approval The study ANV419-001 has been approved by the following Ethics committee:

- HM Hospitals Drug Research Ethics Committee (CEIm) (ID: 20.12.1736-GHM)

- EKNZ – Ethikkommission Nordwest und Zentralschweiz ( ID 2021-00911)

- London – Surrey Borders Research Ethics Committee (ID: 21/LO/0213)

Written consent was obtained from all patients prior taking part into this study.

Consent Written informed consent was obtained from the patient for publication of this abstract.

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