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ePoster Display

1661P - Antitumor efficacy and immune profiling of the mouse ortholog of nemvaleukin alfa, a novel engineered IL-2 fusion protein, in an orthotopic mouse model of small cell lung cancer alone or in combination with standard chemotherapy

Date

16 Sep 2021

Session

ePoster Display

Presenters

Yuanwang Pan

Citation

Annals of Oncology (2021) 32 (suppl_5): S1164-S1174. 10.1016/annonc/annonc680

Authors

Y. Pan1, H. Zhang1, T. Chen1, H. Ding1, H. Han1, C. Almonte1, K.E. Labbe1, S. Nguyen2, J.E. Lopes2, H.C. Losey2, R.J. Winquist2, K. Wong1

Author affiliations

  • 1 Perlmutter Cancer Center, NYU Langone Medical Center, 10016 - New York/US
  • 2 Research, Alkermes, Inc, 02451 - Waltham/US
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Abstract 1661P

Background

Small cell lung cancer (SCLC) is a deadly cancer with a 5-year survival of less than 7%. Immune checkpoint blockade was recently approved but survival benefits are limited. nemvaleukin alfa (‘nemvaleukin’; formerly ALKS 4230), a novel engineered IL-2 fusion protein currently under phase I/II study, is designed to selectively expand tumor-killing CD8+ and NK cells. Here, utilizing a novel SCLC murine model, we investigated the effects of RDB 1462, the murine ortholog of nemvaleukin, on tumor growth and immune cell profiles.

Methods

A novel syngeneic Rb1 -/- p53 -/- p130 -/- (RPP) SCLC model that closely mimics human disease was generated. After confirming tumor burden by magnetic resonance imaging (MRI), mice were treated with RDB 1462 alone or in combination with standard chemotherapy (cisplatin + etoposide). Tumor growth was measured by MRI and survival was recorded. The percentages and functionality of tumor-infiltrating and peripheral blood immune cells were analyzed.

Results

RDB 1462 treatment significantly delayed tumor growth in the SCLC model, which was further enhanced by combining with chemotherapy. Combining RDB 1462 with chemotherapy provided the most significant survival benefits among all treatment groups. Profiling immune cells in tumors after short-term treatment revealed that RDB 1462 expanded the total number of tumor-infiltrating CD8+ T cells. Furthermore, RDB 1462 increased the percentages of activated, effector, and cytotoxic CD8+ T cells in tumors. RDB 1462 treatment also expanded the total number of tumor-associated NK cells and increased the percentage of NK cells expressing the proliferation marker Ki67. Similar findings were observed in the peripheral blood in RDB 1462-treated mice.

Conclusions

The mouse version of nemvaleukin, RDB 1462, demonstrated anti-tumor immunity in a murine model of SCLC. RDB 1462 reduced SCLC growth and prolonged survival in mice, which was further enhanced by combining with standard chemotherapy. The data could potentially support further evaluation of nemvaleukin in the treatment of SCLC either alone or in combination in the clinic.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Alkermes, Inc. and NYU Langone Medical Center.

Funding

Alkermes, Inc.

Disclosure

S. Nguyen: Financial Interests, Institutional, Stocks/Shares: Alkermes, Inc.; Financial Interests, Institutional, Full or part-time Employment: Alkermes, Inc. J.E. Lopes: Financial Interests, Institutional, Stocks/Shares: Alkermes, Inc.; Financial Interests, Institutional, Full or part-time Employment: Alkermes, Inc. H.C. Losey: Financial Interests, Institutional, Stocks/Shares: Alkermes, Inc.; Financial Interests, Institutional, Full or part-time Employment: Alkermes, Inc. R.J. Winquist: Financial Interests, Institutional, Stocks/Shares: Alkermes, Inc.; Financial Interests, Institutional, Full or part-time Employment: Alkermes, Inc. K. Wong: Financial Interests, Personal, Stocks/Shares: G1 Therapeutics; Financial Interests, Institutional, Funding: Takeda; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Mirati; Financial Interests, Institutional, Funding: Alkermes; Financial Interests, Institutional, Funding: Merus; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Ansun Biopharma; Financial Interests, Institutional, Funding: Enliven Therapeutics; Financial Interests, Institutional, Funding: Tvardi Therapeutics; Financial Interests, Institutional, Funding: Delfi Diagnostics; Financial Interests, Institutional, Funding: Dracen Pharmaceuticals; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Recursion; Financial Interests, Personal, Advisory Board: Navire; Financial Interests, Personal, Advisory Board: Prelude; Financial Interests, Personal, Advisory Board: Ono; Financial Interests, Personal and Institutional, Other, Funding & Advisory Board: Janssen; Financial Interests, Personal and Institutional, Other, Funding & Advisory Board: Pfizer; Financial Interests, Personal and Institutional, Other, Funding & Advisory Board: Zentalis. All other authors have declared no conflicts of interest.

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