Phase I study of Nivolumab, an anti-PD-1 antibody, in patients with malignant solid tumors

Investigational New Drugs

Volumn 35, Issue 2, 2017, Pages 207-216

  Yamamoto, Noboru ^a   Nokihara, Hiroshi ^a   Yamada, Yasuhide ^a   Shibata, Takashi ^a   Tamura, Yosuke ^a   Seki, Yoshitaka ^a   Honda, Kazunori ^a   Tanabe, Yuko ^a   Wakui, Hiroshi ^a   Tamura, Tomohide ^a  

^a NATIONAL CANCER CENTER HOSPITAL   (Japan)

Author keywords

Immune checkpoint inhibitor; Nivolumab; Pharmacokinetics; Phase I study

Indexed keywords

C REACTIVE PROTEIN; NIVOLUMAB; RHEUMATOID FACTOR; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY; PDCD1 PROTEIN, HUMAN; PROGRAMMED DEATH 1 RECEPTOR;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALBUMIN BLOOD LEVEL; ANOREXIA; ANTINEOPLASTIC ACTIVITY; ARTICLE; CLINICAL ARTICLE; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DECREASED APPETITE; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; EOSINOPHIL COUNT; ERYTHEMA; FATIGUE; FEMALE; FEVER; FLU LIKE SYNDROME; HEART VENTRICLE EXTRASYSTOLE; HEMATOCRIT; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYPONATREMIA; IMMUNOGENICITY; INJECTION SITE REACTION; JAPANESE (PEOPLE); LACTATE DEHYDROGENASE BLOOD LEVEL; LEUKOCYTE COUNT; LIFE EXPECTANCY; LIOTHYRONINE BLOOD LEVEL; LYMPHOCYTE COUNT; LYMPHOCYTOPENIA; MALAISE; MALE; MALIGNANT NEOPLASM; NAUSEA; PHARMACOKINETICS; PHASE 1 CLINICAL TRIAL; PROTEIN BLOOD LEVEL; PRURITUS; RASH; SIDE EFFECT; SOLID TUMOR; THROMBOCYTOPENIA; THYROTROPIN BLOOD LEVEL; UREA BLOOD LEVEL; URIC ACID BLOOD LEVEL; VOMITING; CLINICAL TRIAL; IMMUNOLOGY; METABOLISM; MIDDLE AGED; NEOPLASM; TREATMENT OUTCOME;

ADULT; AGED; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; FEMALE; HUMANS; MALE; MIDDLE AGED; NEOPLASMS; PROGRAMMED CELL DEATH 1 RECEPTOR; TREATMENT OUTCOME;

EID: 85001575100     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-016-0411-2     Document Type: Article

References (35)

1. 2010 Annual summary of monthly vital statistics (round figure), Statistics and Information Department, Ministry of Welfare and Labour. 8–13, 2011, Ministry of Welfare and Labour
2. Prevalence/mortality/prognosis – 2004 white book for cancer statistics, co-edited by Akira Oshima, Tetsuo Kuroishi, Kazuo Tajima. 201–34, 2004, Shinohara Shuppan Shinsha
3. Oldham RK (1984) Biologicals and biological response modifiers: fourth modality of cancer treatment. Cancer Treat Rep 68:221–232
4. Waldmann TA (2003) Immunotherapy: past, present and future. Nat Med 9:269–277
5. Rosenberg SA, Yang JC, Restifo NP (2004) Cancer immunotherapy: moving beyond current vaccines. Nat Med 10:909–915
6. Francisco LM, Sage PT, Sharpe AH (2010) The PD-1 pathway in tolerance and autoimmunity. Immunol Rev 236:219–242. doi:10.1111/j.1600-065X.2010.00923.x
7. Okazaki T, Honjo T (2006) The PD-1-PD-L pathway in immunological tolerance. Trends Immunol 27:195–201
8. Wang J, Okazaki IM, Yoshida T et al (2010) PD-1 deficiency results in the development of fatal myocarditis in MRL mice. Int Immunol 22:443–452. doi:10.1093/intimm/dxq026
9. Zou W, Chen L (2008) Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8:467–477. doi:10.1038/nri2326
10. Hamanishi J, Mandai M, Iwasaki M et al (2007) Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A 104:3360–3365
11. Hino R, Kabashima K, Kato Y et al (2010) Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer 116:1757–1766. doi:10.1002/cncr.24899
12. Ohigashi Y, Sho M, Yamada Y et al (2005) Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res 11:2947–2953
13. Thompson RH, Kuntz SM, Leibovich BC et al (2006) Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res 66:3381–3385
14. Nomi T, Sho M, Akahori T et al (2007) Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res 13:2151–2157
15. Nakanishi J, Wada Y, Matsumoto K, Azuma M, Kikuchi K, Ueda S (2007) Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol Immunother 56:1173–1182
16. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N (2002) Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A 99:12293–12297
17. Weber JS, D’Angelo SP, Minor D et al (2015) Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 16:375–384. doi:10.1016/S1470-2045(15)70076-8
18. Rizvi NA, Mazières J, Planchard D et al (2015) Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol 16:257–265. doi:10.1016/S1470-2045(15)70054-9
19. Motzer RJ, Rini BI, McDermott DF et al (2015) Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol 33:1430–1437. doi:10.1200/JCO.2014.59.0703
20. Hamanishi J, Mandai M, Ikeda T et al (2015) Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol 33:4015–4022. doi:10.1200/JCO.2015.62.3397
21. Ansell SM, Lesokhin AM, Borrello I et al (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319. doi:10.1056/NEJMoa1411087
22. Guideline in regard to clinical evaluation for anticancer drugs (PFSB/ELD Notification No. 1101001) (2005), November 1
23. Brahmer JR, Drake CG, Wollner I et al (2010) Phase I study of single-agent anti–programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 28:3167–3175. doi:10.1200/JCO.2009.26.7609
24. Brahmer JR, Tykodi SS, Chow LQ et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465. doi:10.1056/NEJMoa1200694
25. Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454. doi:10.1056/NEJMoa1200690
26. Gandini S, Massi D, Mandalà M (2016) PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: a systematic review and meta-analysis. Crit Rev Oncol Hematol 100:88–98. doi:10.1016/j.critrevonc.2016.02.001
27. Ishida Y, Agata Y, Shibahara K, Honjo T (1992) Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 11:3887–3895
28. Topalian SL, Weiner GJ, Pardoll DM (2011) Cancer immunotherapy comes of age. J Clin Oncol 29:4828–4836. doi:10.1200/JCO.2011.38.0899
29. Mellman I, Coukos G, Dranoff G (2011) Cancer immunotherapy comes of age. Nature 480:480–489. doi:10.1038/nature10673
30. Drake CG, Jaffee E, Pardoll DM (2006) Mechanisms of immune evasion by tumors. Adv Immunol 90:51–81. doi:10.1016/S0065-2776(06)90002-9
31. Mizoguchi H, O’Shea JJ, Longo DL, Loeffler CM, McVicar DW, Ochoa AC (1992) Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 258:1795–1798
32. Leach DR, Krummel MF, Allison JP (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271:1734–1736
33. Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723. doi:10.1056/NEJMoa1003466
34. Robert C, Thomas L, Bondarenko I et al (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364:2517–2526. doi:10.1056/NEJMoa1104621
35. Larkin J, Chiarion-Sileni V, Gonzalez R et al (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:23–34. doi:10.1056/NEJMoa1504030