Safety Study of BJ-001, an IL-15 Fusion Protein, for Locally Advanced/Metastatic Solid Tumors

Summary

The purpose of this study is to assess the safety and tolerability of BJ-001, a human IL-15 fusion protein, administered via subcutaneous injections, as a single agent and in combination with pembrolizumab in adult patients with Locally Advanced/Metastatic Solid Tumors

Timeline

Start

2019-12-04

Primary completion

2024-04-29

Completion

2024-10-22

Publications

• Background Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14.
• Background Caudana P, Nunez NG, De La Rochere P, Pinto A, Denizeau J, Alonso R, Niborski LL, Lantz O, Sedlik C, Piaggio E. IL2/Anti-IL2 Complex Combined with CTLA-4, But Not PD-1, Blockade Rescues Antitumor NK Cell Function by Regulatory T-cell Modulation. Cancer Immunol Res. 2019 Mar;7(3):443-457. doi: 10.1158/2326-6066.CIR-18-0697. Epub 2019 Jan 16.
• Background Conlon KC, Lugli E, Welles HC, Rosenberg SA, Fojo AT, Morris JC, Fleisher TA, Dubois SP, Perera LP, Stewart DM, Goldman CK, Bryant BR, Decker JM, Chen J, Worthy TA, Figg WD Sr, Peer CJ, Sneller MC, Lane HC, Yovandich JL, Creekmore SP, Roederer M, Waldmann TA. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. J Clin Oncol. 2015 Jan 1;33(1):74-82. doi: 10.1200/JCO.2014.57.3329. Epub 2014 Nov 17.
• Background Cox L, Larenas-Linnemann D, Lockey RF, Passalacqua G. Speaking the same language: The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System. J Allergy Clin Immunol. 2010 Mar;125(3):569-74, 574.e1-574.e7. doi: 10.1016/j.jaci.2009.10.060. Epub 2010 Feb 7.
• Background Desbois M, Le Vu P, Coutzac C, Marcheteau E, Beal C, Terme M, Gey A, Morisseau S, Teppaz G, Boselli L, Jacques Y, Bechard D, Tartour E, Cassard L, Chaput N. IL-15 Trans-Signaling with the Superagonist RLI Promotes Effector/Memory CD8+ T Cell Responses and Enhances Antitumor Activity of PD-1 Antagonists. J Immunol. 2016 Jul 1;197(1):168-78. doi: 10.4049/jimmunol.1600019. Epub 2016 May 23.
• Background Hensley TR, Easter AB, Gerdts SE, De Rosa SC, Heit A, McElrath MJ, Andersen-Nissen E. Enumeration of major peripheral blood leukocyte populations for multicenter clinical trials using a whole blood phenotyping assay. J Vis Exp. 2012 Sep 16;(67):e4302. doi: 10.3791/4302.
• Background Knudson KM, Hicks KC, Alter S, Schlom J, Gameiro SR. Mechanisms involved in IL-15 superagonist enhancement of anti-PD-L1 therapy. J Immunother Cancer. 2019 Mar 21;7(1):82. doi: 10.1186/s40425-019-0551-y.
• Background Erratum: Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188-195. Blood. 2016 Sep 15;128(11):1533. doi: 10.1182/blood-2016-07-730689.
• Background Lenz HJ. Management and preparedness for infusion and hypersensitivity reactions. Oncologist. 2007 May;12(5):601-9. doi: 10.1634/theoncologist.12-5-601.
• Background Mier JW, Brandon EP, Libby P, Janicka MW, Aronson FR. Activated endothelial cells resist lymphokine-activated killer cell-mediated injury. Possible role of induced cytokines in limiting capillary leak during IL-2 therapy. J Immunol. 1989 Oct 1;143(7):2407-14.
• Background Raedler LA. Opdivo (Nivolumab): Second PD-1 Inhibitor Receives FDA Approval for Unresectable or Metastatic Melanoma. Am Health Drug Benefits. 2015 Mar;8(Spec Feature):180-3. No abstract available.
• Background Rhode PR, Egan JO, Xu W, Hong H, Webb GM, Chen X, Liu B, Zhu X, Wen J, You L, Kong L, Edwards AC, Han K, Shi S, Alter S, Sacha JB, Jeng EK, Cai W, Wong HC. Comparison of the Superagonist Complex, ALT-803, to IL15 as Cancer Immunotherapeutics in Animal Models. Cancer Immunol Res. 2016 Jan;4(1):49-60. doi: 10.1158/2326-6066.CIR-15-0093-T. Epub 2015 Oct 28.
• Background Rosenberg SA. IL-2: the first effective immunotherapy for human cancer. J Immunol. 2014 Jun 15;192(12):5451-8. doi: 10.4049/jimmunol.1490019.
• Background Sim GC, Radvanyi L. The IL-2 cytokine family in cancer immunotherapy. Cytokine Growth Factor Rev. 2014 Aug;25(4):377-90. doi: 10.1016/j.cytogfr.2014.07.018. Epub 2014 Aug 1.
• Background Salmaninejad A, Valilou SF, Shabgah AG, Aslani S, Alimardani M, Pasdar A, Sahebkar A. PD-1/PD-L1 pathway: Basic biology and role in cancer immunotherapy. J Cell Physiol. 2019 Aug;234(10):16824-16837. doi: 10.1002/jcp.28358. Epub 2019 Feb 19.
• Background Waldmann TA. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol. 2006 Aug;6(8):595-601. doi: 10.1038/nri1901.
• Background West EE, Jin HT, Rasheed AU, Penaloza-Macmaster P, Ha SJ, Tan WG, Youngblood B, Freeman GJ, Smith KA, Ahmed R. PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. J Clin Invest. 2013 Jun;123(6):2604-15. doi: 10.1172/JCI67008. Epub 2013 May 15.
• Background Wrangle JM, Velcheti V, Patel MR, Garrett-Mayer E, Hill EG, Ravenel JG, Miller JS, Farhad M, Anderton K, Lindsey K, Taffaro-Neskey M, Sherman C, Suriano S, Swiderska-Syn M, Sion A, Harris J, Edwards AR, Rytlewski JA, Sanders CM, Yusko EC, Robinson MD, Krieg C, Redmond WL, Egan JO, Rhode PR, Jeng EK, Rock AD, Wong HC, Rubinstein MP. ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2018 May;19(5):694-704. doi: 10.1016/S1470-2045(18)30148-7. Epub 2018 Apr 5.

Drugs

Indications

No indication recorded.