ANV419

P1, N=55, Completed, Anaveon AG | Recruiting --> Completed | N=80 --> 55 | Trial completion date: Jan 2025 --> Jul 2024

P2, N=40, Not yet recruiting, Vall d'Hebron Institute of Oncology

Current treatment strategies, such as the use of denosumab, tocilizumab, and emerging agents like bimekizumab and ANV419, highlight the potential of interleukin-targeted therapies in mitigating bone metastases...While not exhaustive, this overview underscores the critical roles of interleukins in bone metastases and highlights the need for continued research to fully elucidate their complex interactions and therapeutic potential. Addressing these gaps will be essential for advancing our understanding and treatment of bone metastases in cancer patients.

ANV419 also enhances the NK cell killing capacity and increases tumor growth inhibition when used alongside trastuzumab in a Her-2+ xenograft mouse model...These data support the clinical development of ANV419 in solid tumors and hematological malignancies as monotherapy and in combination with checkpoint inhibitors or agents that induce antibody-dependent cellular cytotoxicity. ANV419 is currently in Phase 1/2 clinical development and may provide cancer patients with a wider therapeutic window than aldesleukin.

In a separate clinical cohort, we retrospectively measured the residual concentration of nivolumab and pembrolizumab, revealing persistent serum concentrations of anti-PD-1/PD-L1 antibodies even months after treatment cessation. This underscores the importance of comprehensively documenting prior immunotherapy details in clinical trials. Such information is crucial for understanding potential interactions that may impact both immunological and clinical effects.

P1/2, N=130, Recruiting, Anaveon AG | Trial primary completion date: Jun 2024 --> Sep 2024

ANV419 at doses up to 243 µg/kg (the RP2D) was well tolerated and showed signs of antitumor activity in a heavily pretreated patient population with advanced solid tumors.

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.

P1, N=10, Recruiting, University Hospital, Basel, Switzerland | Not yet recruiting --> Recruiting

P1, N=80, Recruiting, Anaveon AG | N=60 --> 80

P1, N=10, Not yet recruiting, University Hospital, Basel, Switzerland

Recombinant IL-2 (proleukin) induces durable responses in approximately 10% of patients with melanoma...In Part 3, the efficacy and safety of ANV419 in combination with the approved doses pembrolizumab or ipilimumab will be evaluated using a Simon’s 2-stage design...Preliminary monotherapy efficacy data are expected by Q1/2024. Clinical trial information: NCT05578872.

The OMNIA-2 study (ANV419-102; NCT 05641324) will evaluate safety and preliminary efficacy of ANV419 as monotherapy and in combination with daratumumab (dara), or lenalidomide with low dose dexamethasone (lena/dex), in patients with relapsed or refractory multiple myeloma...OMNIA-2 is being conducted in Denmark, France, Germany, Spain, Switzerland, UK and enrolment began in January 2023 and preliminary data are expected in Q1 2024. Clinical trial information: NCT05641324.

P1/2, N=130, Recruiting, Anaveon AG | Not yet recruiting --> Recruiting | Trial primary completion date: Mar 2024 --> Jun 2024

P1/2, N=130, Not yet recruiting, Anaveon AG

NK cell killing was analyzed in combination with trastuzumab...Treatment of whole blood with a combination of ANV419 and pembrolizumab (anti-PD1) or ipilimumab (anti-CTLA4) induced only slightly increased cytokine secretion compared to ANV419 alone and is therefore considered to have a reasonable safety profile. Conclusions The data presented here further elucidate the in vitro and in vivo effects of ANV419 and support the rationale for clinical development in indications where NK and CD8 T cells are involved in tumor resolution as well as in combination with ADCC inducing treatments or checkpoint inhibitors.

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...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.

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.

Overall, ANV419 is well tolerated and selectively induces expansion and proliferation of CD8 T cells and NK cells, but not Tregs up to a dose of at least 48mcg/kg. Updated data will be shared during the meeting.

ANV419 is very well tolerated and induces a high degree of proliferation in CD8 T cells and NK cells but not Tregs. ANV419-001 will further evaluate the safety and efficacy of ANV419 alone and in combination with other immunotherapy drugs.

P1/2, N=75, Recruiting, Anaveon AG | Not yet recruiting --> Recruiting

Novel interleukin-2 (IL-2)-based therapeutic modalities with preferential signaling through the IL-2 β/γ receptor (IL-2Rβ/γ) are entering clinical trials and have the potential to substantially increase the therapeutic index of recombinant IL-2 (aldesleukin) for cancer therapy...The combination treatment with anti-HER2 antibody trastuzumab led to an increased anti-tumor activity of the monoclonal antibody in the gastric cancer N87 xenograft model...Aligned to its potent proliferative effect on CD8 and NK cells, ANV419 induces strong anti- tumor responses in various mouse models of cancer. This pre-clinical data and the marked safety window of ANV419 in non-human primates support its translational development as immunotherapeutic agent in oncology.

P1/2, N=75, Not yet recruiting, Anaveon AG