P2, N=396, Recruiting, Nektar Therapeutics | Trial completion date: Dec 2025 --> Dec 2026

P2, N=27, Active, not recruiting, Ascendis Pharma A/S | Recruiting --> Active, not recruiting | N=92 --> 27

Nemvaleukin was well tolerated and demonstrated promising antitumor activity across heavily pretreated advanced solid tumors. Phase 2/3 studies of nemvaleukin are ongoing.

P2, N=162, Recruiting, Philogen S.p.A. | Active, not recruiting --> Recruiting | Initiation date: Dec 2023 --> Jul 2024

P2, N=84, Recruiting, Nektar Therapeutics | Trial completion date: Feb 2026 --> Aug 2026

P3, N=214, Active, not recruiting, Philogen S.p.A. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2028

The addition of Nemvaleukin therapy may enhance responses to RT alone and in combination with anti-PD1.

P2, N=180, Recruiting, Mural Oncology, Inc | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Mar 2024 --> Jun 2025

P3, N=456, Active, not recruiting, Mural Oncology, Inc | Recruiting --> Active, not recruiting

P1/2, N=78, Active, not recruiting, Mural Oncology, Inc | Recruiting --> Active, not recruiting

P1, N=189, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1/2, N=150, Recruiting, Latticon Antibody Therapeutics, Inc | Not yet recruiting --> Recruiting

P3, N=448, Recruiting, Mural Oncology, Inc | Active, not recruiting --> Recruiting | Trial completion date: Dec 2026 --> May 2027 | Trial primary completion date: Dec 2025 --> May 2026

Our model reproduces differential effects of immunotherapy in melanoma patients, capturing the inherent heterogeneity in clinical responses. Taken together, these data demonstrate our model's translatability for novel immunotherapies in melanoma patients. The data are also supportive for the continued clinical investigation of nemvaleukin as a novel immunotherapeutic for the treatment of melanoma.

P3, N=214, Recruiting, Philogen S.p.A. | Trial primary completion date: Dec 2023 --> Oct 2024

P2, N=110, Recruiting, Nektar Therapeutics

P3, N=376, Active, not recruiting, Mural Oncology, Inc | Recruiting --> Active, not recruiting

P2, N=162, Active, not recruiting, Philogen S.p.A.

P1/2, N=150, Not yet recruiting, Latticon Antibody Therapeutics, Inc

P1/2, N=243, Completed, Mural Oncology, Inc | Active, not recruiting --> Completed

P1, N=256, Recruiting, Hoffmann-La Roche | Phase classification: P1a/1b --> P1 | Trial completion date: Nov 2026 --> May 2027 | Trial primary completion date: May 2026 --> Nov 2026

P2, N=396, Recruiting, Nektar Therapeutics

The immune stimulatory mechanisms triggered by NL-201 and RT resulted in superior tumor growth inhibition and survival benefit in both localized and metastatic cancers. Our results support further preclinical and clinical investigation of this novel synergism regimen in locally advanced and metastatic settings.

P2, N=40, Recruiting, Philogen S.p.A. | Trial completion date: Feb 2023 --> Sep 2024 | Trial primary completion date: Nov 2022 --> Sep 2024

The primary end point is investigator-assessed progression-free survival. Clinical Trial Registration: GOG-3063; ENGOT-OV68; NCT05092360 (ClinicalTrials.gov).

The RP2D for monotherapy was determined at 120 mcg/kg IV every 3 weeks while dose escalation continues for combination therapy. PK data indicated a half-life of at least 35 hours and PD data confirm durable activation and expansion of cytotoxic immune cells from TransCon IL-2 β/γ.

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.

Patients must have had â¥1 prior line of platinum-based therapy, â¤5 prior lines of systemic anticancer therapy (platinum-resistant setting), and prior bevacizumab, with radiographic progression on most recent therapy...Approximately 376 patients will be randomised (3:1:1:3) to receive nemvaleukin 6 μg/kg IV (days 1-5)+pembrolizumab 200 mg IV (day 1) of each 21-day cycle, pembrolizumab or nemvaleukin monotherapy, or chemotherapy, and stratified by PD-L1 status, histologic subtype, and chemotherapy (paclitaxel vs others)...Primary endpoint: investigator-assessed progression-free survival (RECIST v1.1) with nemvaleukin+pembrolizumab vs chemotherapy. Secondary/exploratory endpoints include overall survival, other antitumor measures, safety, health-related quality of life, and pharmacokinetic/pharmacodynamic effects.Results Trial in progressConclusion Pending data availability

P1/2, N=78, Recruiting, Alkermes, Inc. | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Mar 2023 --> Jul 2024

In addition, results from clinical trials with Nidlegy in high-risk basal cell carcinoma patients, candidates for disfiguring surgery who experienced durable complete responses, will be shared. Other clinical trial results in “difficult-to-treat tumors” will be discussed.

High-dose recombinant human IL-2 (rhIL-2, aldesleukin) emerged as an important treatment option for selected patients with metastatic melanoma and metastatic renal cell carcinoma, producing durable and long-lasting antitumor responses in a small fraction of patients and heralding the potential of cancer immunotherapy...In this review, we highlight novel drug development strategies, including biochemical modifications and engineered IL-2 variants, to expand the narrow therapeutic window of IL-2 by leveraging downstream activation of the IL-2 receptor to selectively expand anti-tumor CD8-positive T cells and natural killer cells. These modified IL-2 cytokines improve single-agent activity in solid tumor malignancies beyond the established United States Food and Drug Administration (FDA) indications of metastatic melanoma and renal cell carcinoma, and may also be safer in rational combinations with established treatment modalities, including anti-PD-(L)1 and anti-CTLA-4 immunotherapy, chemotherapies, and targeted therapy approaches.

Trial in progress.

TNRX-257 blocks the interaction of LAG3 with MHC-II and enhances TCR signaling with similar potency as Relatlimab. In contrast, the corresponding untargeted IL2Rγ/β Tentacle had no efficacy. Together, these data show that TNRX-257 has drug-like properties and elicits strong anti-tumor efficacy, supporting its clinical development.

MC38 tumor-bearing C57Bl/6 mice were subcutaneously administered murine nemvaleukin alfa (mNemva), an engineered IL-2 immunotherapy that selectively activates and expands cytotoxic NK cells and antigen-experienced CD8+ T cells. Moreover, long-term immunity was 100% effective if the re-challenge experiment was performed out to 5 months after the last dose of mNemva had been administered.Therefore, the neoadjuvant/adjuvant dosing regimen exhibits a superior response in this preclinical model, when combined with partial tumor-debulking surgery, similar to the recent findings in patients with melanoma that were treated with pembrolizumab. In addition, this strategy enables sampling of tumor tissue for analyses of the immune response and the identification of potential predictive markers of response.

In this all autologous humanized melanoma mouse model, nemvaleukin treatment not only enhances T cell engraftment, it significantly augments anti-tumor efficacy. These data support the use of this personalized melanoma xenograft model to analyze the underlying immune responses in responders and non-responders to novel immunotherapies.

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

P2, N=176, Recruiting, Alkermes, Inc. | N=110 --> 176

P1a/1b, N=348, Recruiting, Hoffmann-La Roche | Trial completion date: Jun 2027 --> Nov 2026 | Trial primary completion date: Mar 2027 --> May 2026

mNemvaleukin, a novel cytokine-based immunotherapy, significantly inhibited murine SCLC tumor growth and prolonged survival, which was further enhanced by the addition of chemotherapy. mNemvaleukin alone, and in combination with chemotherapy, drove a strong antitumor immune program elicited by cytotoxic immune cells. Our findings support the evaluation of nemvaleukin alone or in combination with chemotherapy in clinical trials for the treatment of SCLC.

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.