A phase I study of the human monoclonal anti-NRP1 antibody MNRP1685A in patients with advanced solid tumors

Investigational New Drugs

Volumn 32, Issue 4, 2014, Pages 653-660

  Weekes, Colin D ^a   Beeram, Muralidhar ^b   Tolcher, Anthony W ^b   Papadopoulos, Kyriakos P ^b   Gore, Lia ^a   Hegde, Priti ^c   Xin, Yan ^c   Yu, Ron ^c   Shih, L Mason ^c   Xiang, Hong ^c   Brachmann, Rainer K ^c   Patnaik, Amita ^b  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b South Texas Accelerated Research Therapeutics   (United States)

^c GENENTECH INC   (United States)

Author keywords

Clinical trial; MNRP1685A; Neuropilin 1; VEGF

Indexed keywords

MONOCLONAL ANTIBODY; NEUROPILIN 1; VESENCUMAB;

ADULT; AGED; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; DOSE RESPONSE; DRUG ADMINISTRATION; FEMALE; HUMAN; MALE; METABOLISM; MIDDLE AGED; MULTICENTER STUDY; NEOPLASMS; PHASE 1 CLINICAL TRIAL;

ADULT; AGED; ANTIBODIES, MONOCLONAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; MALE; MIDDLE AGED; NEOPLASMS; NEUROPILIN-1;

EID: 84904569660     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-014-0071-z     Document Type: Article

References (23)

1. Tam SJ, Watts RJ (2010) Connecting vascular and nervous system development: angiogenesis and the blood-brain barrier. Annu Rev Neurosci 33:379-408
2. He Z, Tessier-Lavigne M (1997) Neuropilin is a receptor for the axonal chemorepellent semaphorin III. Cell 90:739-51 (Pubitemid 27357965)
3. Soker S, Takashima S, Quan H et al (1998) Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92:735-45 (Pubitemid 28155313)
4. Kawasaki T, Kitsukawa T, Bekku Y (1999) A requirement for neuropilin-1 in embryonic vessel formation. Development 126:4895-902
5. Mamluk R, Gechtman Z, Kutcher ME, Gasiunas N, Gallagher J, Klagsbrun M (2002) Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain. J Biol Chem 277:24818-25 (Pubitemid 34952014)
6. Takashima S, Kitakaze M, Asakura M et al (2002) Targeting of both mouse neuropilin-1 and neuropilin-2 genes severely impairs developmental yolk sac and embryonic angiogenesis. Proc Natl Acad Sci U S A 99:3657-62 (Pubitemid 34252162)
7. Gerhardt H, Ruhrberg C, Abramsson A, Fujisawa H, Shima D, Betsholtz C (2004) Neuropilin-1is required for endothelial tip cell guidance in the developing central nervous system. Dev Dyn 231:503-9 (Pubitemid 39410884)
8. Grandclement C, Borg C (2011) Neuropilins: a new target for cancer therapy. Cancers 3:1899-1928
9. Bielenberg DR, Pettaway CA, Takashima S et al (2006) Neuropilins in neoplasms: expression, regulation, and function. Exp Cell Res 312:584-93 (Pubitemid 43290335)
10. Beck B, Driessens G, Goossens S et al (2011) Avascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumors. Nature 478:399-403
11. Xin Y, Bai S, Damico-Beyer LA et al (2012) Anti-neuropilin-1 (MRNP1685A): unexpected pharmacokinetic differences across species, from preclinical models to humans. Pharm Res 29:2512-21
12. Xin Y, Li J, Wu J, et al. (2012b) Pharmacokinetic and pharmacodynamic analysis of circulating biomarkers of anti-NRP1, a novel antiangiogenesis agent, in two Phase I trials in patients with advanced solid tumors, Clinical Cancer Research, in press.
13. Liang W-C, Dennis MS, Stawicki S et al (2007) Function blocking antibodies to neuropilin-1 generated from a designed human synthetic antibody phage library. J Mol Biol 366:815-29 (Pubitemid 46175863)
14. Pan Q, Chanthery Y, Liang W-C (2007) Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 11:53-67 (Pubitemid 46054517)
15. Bugelski PJ, Achuthanandam R, Capocasale RJ et al (2009) Monoclonal antibody-induced cytokine-release syndrome. Expert Rev Clin Immunol 5:499-521
16. Xia CQ, Peng R, Beato F, Clare-Salzler MJ (2005) Dexamethasone induces IL-10-producing monocyte-derived dendritic cells with durable immaturity. Scand J Immunol 62:45-54 (Pubitemid 41025877)
17. Boks MA, Kager-Groenland JR, Haasjes MS, Zwaginga JJ, van Ham SM, ten Brinke A (2012) IL-10-generated tolerogenic dendritic cells are optimal for functional regulatory T cell induction-a comparative study of human clinical-applicable DC. Clin Immunol 142:332-42
18. Gabay C, Lamacchia C, Palmer G (2010) IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol 6:232-41
19. Darbonne WC, Du X, Dhawan P, et al (2011) Mechanism for platelet reduction in anti-neuropilin-1 (MNRP1685A)-treated phase I patients. J Clin Oncol 29
20. Grothey A, Galanis E (2009) Targeting angiogenesis: progress with anti-VEGF treatment with large molecules. Nat Rev Clin Oncol 6:507-18
21. Raja FA, Chopra N, Ledermann JA (2010) Optimal first-line treatment in ovarian cancer. Ann Oncol 23(10):x118-x127
22. Pellet-Many C, Frankel P, Jia H (2008) Neuropilins: structure, function and role in disease. Biochem J 411:211-26 (Pubitemid 351580173)
23. Pataik A, LoRusso PM, Messersmith W (2013) A Phase Ib study evaluating MNRP1685A, a fully human anti-NRP1 monoclonal antibody, in combination with bevacizumab and paclitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. (in press)