An open-label phase Ib dose-escalation study of TRC105 (anti-endoglin antibody) with bevacizumab in patients with advanced cancer

Clinical Cancer Research

Volumn 20, Issue 23, 2014, Pages 5918-5926

  Gordon, Michael S ^a   Robert, Francisco ^b   Matei, Daniela ^c   Mendelson, David S ^a   Goldman, Jonathan W ^d   Chiorean, E Gabriela ^c,e   Strother, Robert M ^c   Seon, Ben K ^f   Figg, William D ^g   Peer, Cody J ^g   Alvarez, Delia ^h   Adams, Bonne J ^h   Theuer, Charles P ^h   Rosen, Lee S ^d  

^a Pinnacle Oncology Hematology ^*  (United States)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^c INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF WASHINGTON   (United States)

^f ROSWELL PARK CANCER INSTITUTE   (United States)

^g NATIONAL CANCER INSTITUTE   (United States)

^h TRACON Pharmaceuticals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BEVACIZUMAB; CETUXIMAB; DEXAMETHASONE; DIPHENHYDRAMINE; DOXORUBICIN; ENDOGLIN ANTIBODY; FAMOTIDINE; FLUOROURACIL; FOLINIC ACID; IMMUNOGLOBULIN G1 ANTIBODY; IRINOTECAN; MONOCLONAL ANTIBODY; NONSTEROID ANTIINFLAMMATORY AGENT; PARACETAMOL; PROTEIN TYROSINE KINASE INHIBITOR; TOPOTECAN; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR; ANTINEOPLASTIC AGENT; TRC105;

ADULT; ADVANCED CANCER; AGED; ANEMIA; ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTERIAL THROMBOEMBOLISM; ARTICLE; BRAIN ABSCESS; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER PATIENT; CANCER SIZE; CHEMOTHERAPY INDUCED EMESIS; CLINICAL ARTICLE; COHORT ANALYSIS; COLORECTAL CANCER; CONGESTIVE HEART FAILURE; DECREASED APPETITE; DIGESTIVE SYSTEM PERFORATION; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG ERUPTION; DRUG INDUCED HEADACHE; DRUG POTENTIATION; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; DYSPNEA; EPISTAXIS; FACE EDEMA; FATIGUE; FEMALE; FISTULA; FUNCTIONAL STATUS; GINGIVA BLEEDING; GINGIVA PAIN; HEMOPTYSIS; HUMAN; HYPERTENSION; HYPOTHYROIDISM; LUNG HEMORRHAGE; MALE; MIDDLE AGED; MONOTHERAPY; MOUTH PAIN; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NONHUMAN; NOSE OBSTRUCTION; OPEN STUDY; OVARY CANCER; PERIORBITAL EDEMA; PHASE 1 CLINICAL TRIAL; POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME; PROTEINURIA; RECOMMENDED DRUG DOSE; SINGLE DRUG DOSE; SOLID TUMOR; TELANGIECTASIA; THERAPY DELAY; TREATMENT RESPONSE; VERY ELDERLY; WOUND HEALING IMPAIRMENT; CANCER STAGING; CLINICAL TRIAL; MAXIMUM TOLERATED DOSE; NEOPLASMS; PATHOLOGY; TREATMENT OUTCOME;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; FEMALE; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASM STAGING; NEOPLASMS; TREATMENT OUTCOME;

EID: 84918799506     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-14-1143     Document Type: Article

References (42)

1. Potente M, Gerhardt H, Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell 2011;146:873-87.
2. Escudier B, Bellmunt J, Negrier S, Bajetta E, Melichar B, Bracarda S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 2010;28:2144-50.
3. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335-42.
4. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-90.
5. Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patientswith previously treated metastatic breast cancer. J Clin Oncol 2005;23:792-9.
6. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006;355:2542-50.
7. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009;27:4733-40.
8. Seon BK, Haba A, Matsuno F, Takahashi N, Tsujie M, She X, et al. Endoglin-targeted cancer therapy. Curr Drug Deliv 2011;8:135-43.
9. Rosen L, Gordon M, Robert F, Matei D. Endoglin for targeted cancer treatment. Current oncology reports 2014;16:365.
10. Sanchez-Elsner T, Botella LM, Velasco B, Langa C, Bernabeu C. Endoglin expression is regulated by transcriptional cooperation between the hypoxia and transforming growth factor-beta pathways. J Biol Chem 2002;277:43799-808.
11. Bockhorn M, Tsuzuki Y, Xu L, Frilling A, Broelsch CE, Fukumura D. Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts. Clin Cancer Res 2003;9:4221-6.
12. Davis DW, Inoue K, Dinney CP, Hicklin DJ, Abbruzzese JL, McConkey DJ. Regional effects of an antivascular endothelial growth factor receptor monoclonal antibody on receptor phosphorylation and apoptosis in human 253J B-V bladder cancer xenografts. Cancer Res 2004;64:4601-10.
13. Anderberg C, Cunha SI, Zhai Z, Cortez E, Pardali E, Johnson JR, et al. Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination. J Exp Med 2013;210:563-79.
14. Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, et al. Defective angiogenesis in mice lacking endoglin. Science 1999;284: 1534-7.
15. Duarte C, Murray K, Lucas F, Fairfield K, Miller H, Brooks P, et al. Improved survival outcomes in cancer patients with hereditary hemorrhagic telangiectasia. Cancer Epidemiol Biomarkers Prev 2014;23: 117-25.
16. Lenato GM, Guanti G. Hereditary haemorrhagic telangiectasia (HHT): genetic and molecular aspects. Curr Pharm Des 2006;12: 1173-93.
17. Kumar S, Ghellal A, Li C, Byrne G, Haboubi N, Wang JM, et al. Breast carcinoma: vascular density determined using CD105 antibody correlates with tumor prognosis. Cancer Res 1999;59:856-61.
18. Duff SE, Li C, Garland JM, Kumar S. CD105 is important for angiogenesis: evidence and potential applications. FASEB J 2003;17:984-92.
19. Li C, Gardy R, Seon BK, Duff SE, Abdalla S, Renehan A, et al. Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis. Br J Cancer 2003;88:1424-31.
20. Saad RS, El-Gohary Y, Memari E, Liu YL, Silverman JF. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma. Hum Pathol 2005;36:955-61.
21. Yao Y, Kubota T, Takeuchi H, Sato K. Prognostic significance of microvessel density determined by an anti-CD105/endoglin monoclonal antibody in astrocytic tumors: comparison with an anti-CD31 monoclonal antibody. Neuropathology 2005;25:201-6.
22. Ding S, Li C, Lin S, Yang Y, Liu D, Han Y, et al. Comparative evaluation of microvessel density determined by CD34 or CD105 in benign and malignant gastric lesions. Hum Pathol 2006;37:861-6.
23. Erdem O, Taskiran C, Onan MA, Erdem M, Guner H, Ataoglu O. CD105 expression is an independent predictor of survival in patients with endometrial cancer. Gynecol Oncol 2006;103:1007-11.
24. Kyzas PA, Agnantis NJ, Stefanou D. Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma. Virchows Arch 2006;448:768-75.
25. Marioni G, Marino F, Giacomelli L, Staffieri C, Mariuzzi ML, Violino E, et al. Endoglin expression is associated with poor oncologic outcome in oral and oropharyngeal carcinoma. Acta Otolaryngol 2006;126:633-9.
26. Taskiran C, Erdem O, Onan A, Arisoy O, Acar A, Vural C, et al. The prognostic value of endoglin (CD105) expression in ovarian carcinoma. Int J Gynecol Cancer 2006;16:1789-93.
27. Yang LY, Lu WQ, Huang GW, Wang W. Correlation between CD105 expression and postoperative recurrence and metastasis of hepatocellular carcinoma. BMC Cancer 2006;6:110.
28. El-Gohary YM, Silverman JF, Olson PR, Liu YL, Cohen JK, Miller R, et al. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in prostatic adenocarcinoma. Am J Clin Pathol 2007;127:572-9.
29. Rubatt JM, Darcy KM, Hutson A, Bean SM, Havrilesky LJ, Grace LA, et al. Independent prognostic relevance of microvessel density in advanced epithelial ovarian cancer and associations between CD31, CD105, p53 status, and angiogenic marker expression: a Gynecologic Oncology Group study. Gynecol Oncol 2009;112:469-74.
30. Dallas NA, Samuel S, Xia L, Fan F, Gray MJ, Lim SJ, et al. Endoglin (CD105): a marker of tumor vasculature and potential target for therapy. Clin Cancer Res 2008;14:1931-7.
31. Nolan-Stevaux O, Zhong W, Culp S, Shaffer K, Hoover J, Wickramasinghe D, et al. Endoglin requirement for BMP9 signaling in endothelial cells reveals new mechanism of action for selective anti-endoglin antibodies. PLoS ONE 2012;7:e50920.
32. Rosen L, Hurwitz H, Wong M, Goldman J, Mendelson D, Figg W, et al. A phase I first-in-human study of TRC105 (Anti-Endoglin Antibody) in patients with advanced cancer. Clin Cancer Res 2012;18:4820-9.
33. Shiozaki K, Harada N, Greco WR, Haba A, Uneda S, Tsai H, et al. Antiangiogenic chimeric anti-endoglin (CD105) antibody: pharmacokinetics and immunogenicity in nonhuman primates and effects of doxorubicin. Cancer Immunol Immunother 2006;55:140-50.
34. Duffaud F, Therasse P. [New guidelines to evaluate the response to treatment in solid tumors]. Bull Cancer 2000;87:881-6.
35. Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 2007;25:1753-9.
36. Rosen LS, Hurwitz HI, Wong MK, Goldman J, Mendelson DS, Figg WD, et al.. A phase I first-in-human study of TRC 105 (Anti-Endoglin Antibody) in patients with advanced cancer. Clin Cancer Res 2012;18:4820-9.
37. Korn RL, Gordon MS, Rosen LS, Robert F, Matei D, Goldman JW, et al.. Exploratory textural CT evaluation of the combination of TRC 105 (antiendoglin monoclonal antibody; MAb) and bevacizumab (BEV) indicates partial response by Choi criteria in BEV refractory advanced cancer patients (pts) and identifies candidate markers of response. Mol Cancer Ther 2013;12(11 Suppl):A2.
38. Bukowski R, Kabbinavar F, Figlin R, Flaherty K, Srinivas S, Vaishampayan U, et al. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol 2007;25:4536-41.
39. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 2008;8:592.
40. Sennino B, Ishiguro-Oonuma T, Wei Y, Naylor R, Williamson C, Bhagwandin V, et al. Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumors. Cancer Discov 2012;2:270-87.
41. Anderberg C, Cunha SI, Zhai Z, Cortez E, Pardali E, Johnson JR, et al. Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination. J Exp Med 2013;210:563-79.
42. Pàez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Viñals F, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer cell 2009;15:220-31.