Design and characterization of MP0250, a tri-specific anti-HGF/anti-VEGF DARPin® drug candidate

References

• Binz HK, Amstutz P, Plückthun A. Engineering novel binding proteins from nonimmunoglobulin domains. Nat Biotechnol. 2005;23:1257–68. doi:10.1038/nbt1127. PMID:16211069
   PubMed Web of Science ®Google Scholar
• Vazquez-Lombardi R, Phan TG, Zimmermann C, Lowe D, Jermutus L, Christ D. Challenges and opportunities for non-antibody scaffold drugs. Drug Discov Today. 2015;20:1271–83. doi:10.1016/j.drudis.2015.09.004. PMID:26360055
   PubMed Web of Science ®Google Scholar
• Binz HK, Amstutz P, Kohl A, Stumpp MT, Briand C, Forrer P, Grütter MG, Plückthun A. High-affinity binders selected from designed ankyrin repeat protein libraries. Nat Biotechnol. 2004;22:575–82. doi:10.1038/nbt962. PMID:15097997
   PubMed Web of Science ®Google Scholar
• Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature. 2005;438:967–74. doi:10.1038/nature04483. PMID:16355214
   PubMed Web of Science ®Google Scholar
• Comoglio PM, Giordano S, Trusolino L. Drug development of MET inhibitors: Targeting oncogene addiction and expedience. Nat Rev Drug Discov. 2008;7:504–16. doi:10.1038/nrd2530. PMID:18511928
   PubMed Web of Science ®Google Scholar
• Escudier B. Anti-VEGF therapy for renal cell carcinoma. Clin Adv Hematol Oncol. 2007;5:530–1. PMID:17679926
   PubMedGoogle Scholar
• Hurwitz H. Integrating the anti-VEGF-A humanized monoclonal antibody bevacizumab with chemotherapy in advanced colorectal cancer. Clin Colorectal Cancer. 2004;4(Suppl 2):S62–8. doi:10.3816/CCC.2004.s.010. PMID:15479481
   PubMedGoogle Scholar
• Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008;358:2039–49. doi:10.1056/NEJMra0706596. PMID:18463380
   PubMed Web of Science ®Google Scholar
• Jahangiri A, De Lay M, Miller LM, Carbonell WS, Hu YL, Lu K, Tom MW, Paquette J, Tokuyasu TA, Tsao S, et al. Gene expression profile identifies tyrosine kinase c-Met as a targetable mediator of antiangiogenic therapy resistance. Clin Cancer Res. 2013;19:1773–83. doi:10.1158/1078-0432.CCR-12-1281. PMID:23307858
   PubMed Web of Science ®Google Scholar
• Castellone MD, Carlomagno F, Salvatore G, Santoro M. Receptor tyrosine kinase inhibitors in thyroid cancer. Best Pract Res Clin Endocrinol Metab. 2008;22:1023–38. doi:10.1016/j.beem.2008.09.012. PMID:19041829
   PubMed Web of Science ®Google Scholar
• Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10:2298–308. doi:10.1158/1535-7163.MCT-11-0264. PMID:21926191
   PubMed Web of Science ®Google Scholar
• Smith DC, Smith MR, Sweeney C, Elfiky AA, Logothetis C, Corn PG, Vogelzang NJ, Small EJ, Harzstark AL, Gordon MS, et al. Cabozantinib in patients with advanced prostate cancer: Results of a phase II randomized discontinuation trial. J Clin Oncol. 2013;31:412–9. doi:10.1200/JCO.2012.45.0494. PMID:23169517
   PubMed Web of Science ®Google Scholar
• Basilico C, Pennacchietti S, Vigna E, Chiriaco C, Arena S, Bardelli A, Valdembri D, Serini G, Michieli P. Tivantinib (ARQ197) displays cytotoxic activity that is independent of its ability to bind MET. Clin Cancer Res. 2013;19:2381–92. doi:10.1158/1078-0432.CCR-12-3459. PMID:23532890
   PubMed Web of Science ®Google Scholar
• Michieli P, Basilico C, Pennacchietti S. Tivantinib (ARQ197) displays cytotoxic activity that is independent of its ability to bind MET–response. Clin Cancer Res. 2013;19:4291. doi:10.1158/1078-0432.CCR-13-1534. PMID:23766360
   PubMed Web of Science ®Google Scholar
• Jayaram A, Zafeiriou Z, de Bono JS. Cabozantinib-getting under the skin of cutaneous toxicity. JAMA Oncol. 2015;1:535–6. doi:10.1001/jamaoncol.2015.0702. PMID:26181263
   PubMed Web of Science ®Google Scholar
• Belum VR, Serna-Tamayo C, Wu S, Lacouture ME. Incidence and risk of hand-foot skin reaction with cabozantinib, a novel multikinase inhibitor: A meta-analysis. Clin Exp Dermatol. 2016;41:8–15. doi:10.1111/ced.12694. PMID:26009777
   PubMed Web of Science ®Google Scholar
• Greenall SA, Adams TE, Johns TG. Incomplete target neutralization by the anti-cancer antibody rilotumumab. mAbs. 2016;8:246–52. doi:10.1080/19420862.2015.1122149. PMID:26750997
   PubMed Web of Science ®Google Scholar
• Gordon MS, Sweeney CS, Mendelson DS, Eckhardt SG, Anderson A, Beaupre DM, Branstetter D, Burgess TL, Coxon A, Deng H, et al. Safety, pharmacokinetics, and pharmacodynamics of AMG 102, a fully human hepatocyte growth factor-neutralizing monoclonal antibody, in a first-in-human study of patients with advanced solid tumors. Clin Cancer Res. 2010;16:699–710. doi:10.1158/1078-0432.CCR-09-1365. PMID:20068101
   PubMed Web of Science ®Google Scholar
• Ryan CJ, Rosenthal M, Ng S, Alumkal J, Picus J, Gravis G, Fizazi K, Forget F, Machiels JP, Srinivas S, et al. Targeted MET inhibition in castration-resistant prostate cancer: A randomized phase II study and biomarker analysis with rilotumumab plus mitoxantrone and prednisone. Clin Cancer Res. 2013;19:215–24. doi:10.1158/1078-0432.CCR-12-2605. PMID:23136195
   PubMed Web of Science ®Google Scholar
• Cunningham D, Tebbutt NC, Davidenko I, Murad AM, Al-Batran S-E, Ilson DH, Tjulandin S, Gotovkin E, Karaszewska B, Bondarenko I. Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study. J Clin Oncol. 2015;33:4000–4000. abstract 4000.
   Web of Science ®Google Scholar
• Merchant M, Ma X, Maun HR, Zheng Z, Peng J, Romero M, Huang A, Yang NY, Nishimura M, Greve J, et al. Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent. Proc Natl Acad Sci U S A. 2013;110:E2987–96. doi:10.1073/pnas.1302725110. PMID:23882082
   PubMed Web of Science ®Google Scholar
• Finisguerra V, Prenen H, Mazzone M. Preclinical and clinical evaluation of MET functions in cancer cells and in the tumor stroma. Oncogene. 2016;35(42):5457–5467. doi:10.1038/onc.2016.36. PMID:26996670
   PubMed Web of Science ®Google Scholar
• Spigel DR, Edelman MJ, O'Byrne K, Paz-Ares L, Mocci S, Phan S, Shames DS, Smith D, Yu W, Paton VE, et al. Results from the phase III randomized trial of onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIB or IV non-small-cell lung cancer: METLung. J Clin Oncol. 2017;35:412–20. doi:10.1200/JCO.2016.69.2160. PMID:27937096
   PubMed Web of Science ®Google Scholar
• Rolfo C, Van Der Steen N, Pauwels P, Cappuzzo F. Onartuzumab in lung cancer: The fall of Icarus? Expert Rev Anticancer Ther. 2015;15:487–9. doi:10.1586/14737140.2015.1031219. PMID:25818471
   PubMed Web of Science ®Google Scholar
• Fiedler U, Ekawardhani S, Cornelius A, Gilboy P, Bakker TR, Dolado I, Stumpp MT, Dawson KM. MP0250, a VEGF and HGF neutralizing DARPin® molecule shows high anti-tumor efficacy in mouse xenograft and patient-derived tumor models. OncoTarget [in press].
   Google Scholar
• Binz HK, Stumpp MT, Forrer P, Amstutz P, Plückthun A. Designing repeat proteins: Well-expressed, soluble and stable proteins from combinatorial libraries of consensus ankyrin repeat proteins. J Mol Biol. 2003;332:489–503. PMID:12948497
   PubMed Web of Science ®Google Scholar
• Stahl A, Stumpp MT, Schlegel A, Ekawardhani S, Lehrling C, Martin G, Gulotti-Georgieva M, Villemagne D, Forrer P, Agostini HT, et al. Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications. Angiogenesis. 2013;16:101–11. doi:10.1007/s10456-012-9302-0. PMID:22983424
   PubMed Web of Science ®Google Scholar
• Zahnd C, Kawe M, Stumpp MT, de Pasquale C, Tamaskovic R, Nagy-Davidescu G, Dreier B, Schibli R, Binz HK, Waibel R, et al. Efficient tumor targeting with high-affinity designed ankyrin repeat proteins: Effects of affinity and molecular size. Cancer Res. 2010;70:1595–605. doi:10.1158/0008-5472.CAN-09-2724. PMID:20124480
   PubMed Web of Science ®Google Scholar
• Ståhl S, Nygren PA. The use of gene fusions to protein A and protein G in immunology and biotechnology. Pathol Biol. 1997;45:66–76. PMID:9097850
   PubMed Web of Science ®Google Scholar
• Steiner D, Merz FW, Sonderegger I, Gulotti-Georgieva M, Villemagne D, Phillips DJ, Forrer P, Stumpp MT, Zitt C, Binz HK. Half-life extension using serum albumin-binding DARPin® domains. Prot Eng Des Selection. [in press].
   Google Scholar
• Ings RM. Interspecies scaling and comparisons in drug development and toxicokinetics. Xenobiotica. 1990;20:1201–31. doi:10.3109/00498259009046839. PMID:2275215
   PubMed Web of Science ®Google Scholar
• Ling J, Zhou H, Jiao Q, Davis HM. Interspecies scaling of therapeutic monoclonal antibodies: Initial look. J Clin Pharmacol. 2009;49:1382–402. doi:10.1177/0091270009337134. PMID:19837907
   PubMed Web of Science ®Google Scholar
• Lin YS, Nguyen C, Mendoza JL, Escandon E, Fei D, Meng YG, Modi NB. Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor. J Pharmacol Exp Ther. 1999;288:371–8. PMID:9862791
   PubMed Web of Science ®Google Scholar
• Kawe M, Horn U, Plückthun A. Facile promoter deletion in Escherichia coli in response to leaky expression of very robust and benign proteins from common expression vectors. Microb Cell Fact. 2009;8:8. doi:10.1186/1475-2859-8-8. PMID:19171063
   PubMed Web of Science ®Google Scholar