An Autologous NK/CIK Cell Product (PB101) in Combination With EGFR-TKI for Treating Lung Cancer

Summary

This study was designed to determine the safety and tolerability of PB101 (autologous NK cell product) in combination with standard of care EGFR-TKI in patients with EGFR-mutated advanced non-small cell lung cancer.

Timeline

Start

2018-09-01

Primary completion

2019-08-01

Completion

2023-12-01

Publications

• Results Zhang Q, Liu XY, Zhang T, Zhang XF, Zhao L, Long F, Liu ZK, Wang EH. The dual-functional capability of cytokine-induced killer cells and application in tumor immunology. Hum Immunol. 2015 May;76(5):385-91. doi: 10.1016/j.humimm.2014.09.021. Epub 2014 Oct 8.
• Results Woan K, Reddy V. Potential therapeutic role of natural killer cells in cancer. Expert Opin Biol Ther. 2007 Jan;7(1):17-29. doi: 10.1517/14712598.7.1.17.
• Results Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, Thompson CB, Griesser H, Mak TW. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995 Nov 10;270(5238):985-8. doi: 10.1126/science.270.5238.985.
• Results Ware KE, Hinz TK, Kleczko E, Singleton KR, Marek LA, Helfrich BA, Cummings CT, Graham DK, Astling D, Tan AC, Heasley LE. A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop. Oncogenesis. 2013 Mar 25;2(3):e39. doi: 10.1038/oncsis.2013.4.
• Results Mollet TW, Garcia CA, Koester G. Skin metastases from lung cancer. Dermatol Online J. 2009 May 15;15(5):1.
• Results Thompson CB, Allison JP. The emerging role of CTLA-4 as an immune attenuator. Immunity. 1997 Oct;7(4):445-50. doi: 10.1016/s1074-7613(00)80366-0. No abstract available.
• Results Small EJ, Fratesi P, Reese DM, Strang G, Laus R, Peshwa MV, Valone FH. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol. 2000 Dec 1;18(23):3894-903. doi: 10.1200/JCO.2000.18.23.3894.
• Results Shi SB, Tang XY, Tian J, Chang CX, Li P, Qi JL. Efficacy of erlotinib plus dendritic cells and cytokine-induced killer cells in maintenance therapy of advanced non-small cell lung cancer. J Immunother. 2014 May;37(4):250-5. doi: 10.1097/CJI.0000000000000015.
• Results Sheng J, Fang W, Liu X, Xing S, Zhan J, Ma Y, Huang Y, Zhou N, Zhao H, Zhang L. Impact of gefitinib in early stage treatment on circulating cytokines and lymphocytes for patients with advanced non-small cell lung cancer. Onco Targets Ther. 2017 Feb 21;10:1101-1110. doi: 10.2147/OTT.S112158. eCollection 2017.
• Results Seino K, Motohashi S, Fujisawa T, Nakayama T, Taniguchi M. Natural killer T cell-mediated antitumor immune responses and their clinical applications. Cancer Sci. 2006 Sep;97(9):807-12. doi: 10.1111/j.1349-7006.2006.00257.x. Epub 2006 Jun 29.
• Results Segal NH, Parsons DW, Peggs KS, Velculescu V, Kinzler KW, Vogelstein B, Allison JP. Epitope landscape in breast and colorectal cancer. Cancer Res. 2008 Feb 1;68(3):889-92. doi: 10.1158/0008-5472.CAN-07-3095.
• Results Perez VL, Van Parijs L, Biuckians A, Zheng XX, Strom TB, Abbas AK. Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement. Immunity. 1997 Apr;6(4):411-7. doi: 10.1016/s1074-7613(00)80284-8.
• Results Parkhurst MR, Riley JP, Dudley ME, Rosenberg SA. Adoptive transfer of autologous natural killer cells leads to high levels of circulating natural killer cells but does not mediate tumor regression. Clin Cancer Res. 2011 Oct 1;17(19):6287-97. doi: 10.1158/1078-0432.CCR-11-1347. Epub 2011 Aug 15.
• Results Ocean AJ, Vahdat LT. Chemotherapy-induced peripheral neuropathy: pathogenesis and emerging therapies. Support Care Cancer. 2004 Sep;12(9):619-25. doi: 10.1007/s00520-004-0657-7.
• Results Niu Q, Wang W, Li Y, Qin S, Wang Y, Wan G, Guan J, Zhu W. Cord blood-derived cytokine-induced killer cells biotherapy combined with second-line chemotherapy in the treatment of advanced solid malignancies. Int Immunopharmacol. 2011 Apr;11(4):449-56. doi: 10.1016/j.intimp.2010.12.014. Epub 2011 Jan 5.
• Results Morgillo F, Della Corte CM, Fasano M, Ciardiello F. Mechanisms of resistance to EGFR-targeted drugs: lung cancer. ESMO Open. 2016 May 11;1(3):e000060. doi: 10.1136/esmoopen-2016-000060. eCollection 2016.
• Results Lee JH, Lee JH, Lim YS, Yeon JE, Song TJ, Yu SJ, Gwak GY, Kim KM, Kim YJ, Lee JW, Yoon JH. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology. 2015 Jun;148(7):1383-91.e6. doi: 10.1053/j.gastro.2015.02.055. Epub 2015 Mar 4.
• Results Kirkwood JM, Tarhini AA, Panelli MC, Moschos SJ, Zarour HM, Butterfield LH, Gogas HJ. Next generation of immunotherapy for melanoma. J Clin Oncol. 2008 Jul 10;26(20):3445-55. doi: 10.1200/JCO.2007.14.6423.
• Results Kim H, Kim SH, Kim MJ, Kim SJ, Park SJ, Chung JS, Bae JH, Kang CD. EGFR inhibitors enhanced the susceptibility to NK cell-mediated lysis of lung cancer cells. J Immunother. 2011 May;34(4):372-81. doi: 10.1097/CJI.0b013e31821b724a.
• Results Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.
• Results Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med. 2006 Sep 21;355(12):1253-61. doi: 10.1056/NEJMra061808. No abstract available.
• Results Jin S, Deng Y, Hao JW, Li Y, Liu B, Yu Y, Shi FD, Zhou QH. NK cell phenotypic modulation in lung cancer environment. PLoS One. 2014 Oct 9;9(10):e109976. doi: 10.1371/journal.pone.0109976. eCollection 2014.
• Results He S, Yin T, Li D, Gao X, Wan Y, Ma X, Ye T, Guo F, Sun J, Lin Z, Wang Y. Enhanced interaction between natural killer cells and lung cancer cells: involvement in gefitinib-mediated immunoregulation. J Transl Med. 2013 Aug 12;11:186. doi: 10.1186/1479-5876-11-186.
• Results Gutierrez-Gutierrez G, Sereno M, Miralles A, Casado-Saenz E, Gutierrez-Rivas E. Chemotherapy-induced peripheral neuropathy: clinical features, diagnosis, prevention and treatment strategies. Clin Transl Oncol. 2010 Feb;12(2):81-91. doi: 10.1007/S12094-010-0474-z.
• Results Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, Chao TY, Nakagawa K, Chu DT, Saijo N, Duffield EL, Rukazenkov Y, Speake G, Jiang H, Armour AA, To KF, Yang JC, Mok TS. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011 Jul 20;29(21):2866-74. doi: 10.1200/JCO.2010.33.4235. Epub 2011 Jun 13.
• Results Chang N, Duan J, Wang L, Dong Z, Liu Z. Patients with advanced non-small cell lung cancer with EGFR mutations in addition to complex mutations treated with osimertinib have a poor clinical outcome: A real-world data analysis. Oncol Lett. 2020 Sep;20(3):2266-2272. doi: 10.3892/ol.2020.11801. Epub 2020 Jul 1.
• Results Bour-Jordan H, Esensten JH, Martinez-Llordella M, Penaranda C, Stumpf M, Bluestone JA. Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family. Immunol Rev. 2011 May;241(1):180-205. doi: 10.1111/j.1600-065X.2011.01011.x.
• Results Boivin JF. Second cancers and other late side effects of cancer treatment. A review. Cancer. 1990 Feb 1;65(3 Suppl):770-5. doi: 10.1002/1097-0142(19900201)65:3+3.0.co;2-8.
• Results Beijers AJ, Jongen JL, Vreugdenhil G. Chemotherapy-induced neurotoxicity: the value of neuroprotective strategies. Neth J Med. 2012 Jan;70(1):18-25.
• Results Baxevanis CN, Gritzapis AD, Tsitsilonis OE, Katsoulas HL, Papamichail M. HER-2/neu-derived peptide epitopes are also recognized by cytotoxic CD3(+)CD56(+) (natural killer T) lymphocytes. Int J Cancer. 2002 Apr 20;98(6):864-72. doi: 10.1002/ijc.10251.

Drugs

Indications