Phase I/II trial of labetuzumab govitecan (Anti-CEACAM5/ SN-38 Antibody-Drug Conjugate) in patients with refractory or relapsing metastatic colorectal cancer

Journal of Clinical Oncology

Volumn 35, Issue 29, 2017, Pages 3338-3346

  Dotan, Efrat ^a   Cohen, Steven J ^a   Starodub, Alexander N ^b   Lieu, Christopher H ^c   Messersmith, Wells A ^c   Simpson, Pamela S ^d   Guarino, Michael J ^d   Marshall, John L ^e   Goldberg, Richard M ^e   Hecht, J Randolph ^f   Wegener, William A ^g   Sharkey, Robert M ^g   Govindan, Serengulam V ^h   Goldenberg, David M ⁱ   Berlin, Jordan D ^a  

^a FOX CHASE CANCER CENTER   (United States)

^b INDIANA UNIVERSITY HEALTH   (United States)

^c UNIVERSITY OF COLORADO CANCER CENTER   (United States)

^d HELEN F GRAHAM CANCER CENTER   (United States)

^e GEORGETOWN UNIVERSITY HOSPITAL   (United States)

^f OHIO STATE UNIVERSITY   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

^h Immunomedics   (United States)

ⁱ VANDERBILT INGRAM CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY DRUG CONJUGATE; CARCINOEMBRYONIC ANTIGEN; IRINOTECAN; LABETUZUMAB GOVITECAN; ANTINEOPLASTIC AGENT; CAMPTOTHECIN; MONOCLONAL ANTIBODY;

ABDOMINAL PAIN; ADULT; AGED; ALOPECIA; ANEMIA; ANOREXIA; ARTICLE; CANCER PATIENT; COHORT ANALYSIS; CONSTIPATION; DIARRHEA; DRUG CLEARANCE; DRUG DOSE REGIMEN; DRUG HALF LIFE; DRUG SAFETY; DRUG WITHDRAWAL; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; HUMAN; HYPERBILIRUBINEMIA; HYPERGLYCEMIA; HYPONATREMIA; LEUKOPENIA; LYMPHOCYTOPENIA; MAJOR CLINICAL STUDY; MALE; METASTATIC COLORECTAL CANCER; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RESPONSE EVALUATION CRITERIA IN SOLID TUMORS; SMALL INTESTINE OBSTRUCTION; THROMBOCYTOPENIA; TREATMENT RESPONSE; TUMOR IMMUNOGENICITY; VOMITING; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; COLORECTAL NEOPLASMS; DISEASE COURSE; DISEASE FREE SURVIVAL; DRUG ADMINISTRATION; DRUG RESISTANCE; HALF LIFE TIME; INTRAVENOUS DRUG ADMINISTRATION; METASTASIS; MIDDLE AGED; MORTALITY; PATHOLOGY; SURVIVAL ANALYSIS; TREATMENT OUTCOME; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; CAMPTOTHECIN; COLORECTAL NEOPLASMS; DISEASE PROGRESSION; DISEASE-FREE SURVIVAL; DRUG ADMINISTRATION SCHEDULE; DRUG RESISTANCE, NEOPLASM; FEMALE; HALF-LIFE; HUMANS; INFUSIONS, INTRAVENOUS; MALE; MIDDLE AGED; NEOPLASM METASTASIS; SURVIVAL ANALYSIS; TREATMENT OUTCOME;

EID: 85031946497     PISSN: 0732183X     EISSN: 15277755     Source Type: Journal    
DOI: 10.1200/JCO.2017.73.9011     Document Type: Article

References (43)

1. Siegel RL, Miller KD, Fedewa SA, et al: Colorectal cancer statistics, 2017. CA Cancer J Clin 67: 177-193, 2017
2. Siegel RL, Miller KD, Jemal A: Cancer Statistics, 2017. CA Cancer J Clin 67:7-30, 2017
3. Van Cutsem E, Cervantes A, Nordlinger B, et al: Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 25:iii1-iii9, 2014
4. Bertocchi P, Aroldi F, Prochilo T, et al: Chemotherapy rechallenge after regorafenib treatment in metastatic colorectal cancer: Still hope after the last hope? J Chemother 29:102-105, 2017
5. Nappi A, Berretta M, Romano C, et al: Metastatic colorectal cancer: Role of target therapies and future perspectives. Curr Cancer Drug Targets 10.2174/1568009617666170209095143 [epub ahead of print on February 8, 2017]
6. Blumenthal RD, Leon E, Hansen HJ, et al: Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers. BMC Cancer 7:2, 2007
7. Fakih MG: Metastatic colorectal cancer: Current state and future directions. J Clin Oncol 33: 1809-1824, 2015
8. Recondo G Jr, Diaz-Canto n E, de la Vega M, et al: Advances and new perspectives in the treatment of metastatic colon cancer. World J Gastrointest Oncol 6:211-224, 2014
9. Casi G, Neri D: Antibody-drug conjugates and small molecule-drug conjugates: Opportunities and challenges for the development of selective anticancer cytotoxic agents. J Med Chem 58:8751-8761, 2015
10. Esteva FJ, Miller KD, Teicher BA: What can we learn about antibody-drug conjugates from the T-DM1 experience? Am Soc Clin Oncol Educ Book e117-e125, 2015
11. Peters C, Brown S: Antibody-drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep 35:e00225, 2015
12. Beck A, Goetsch L, Dumontet C, et al: Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov 16: 315-337, 2017
13. Garcia-Carbonero R, Supko JG: Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins. Clin Cancer Res 8:641-661, 2002
14. Mathijssen RH, van Alphen RJ, Verweij J, et al: Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res 7:2182-2194, 2001
15. Stein A, Voigt W, Jordan K: Chemotherapyinduced diarrhea: Pathophysiology, frequency and guideline-based management. Ther Adv Med Oncol 2:51-63, 2010
16. Govindan SV, Cardillo TM, Moon SJ, et al: CEACAM5-targeted therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 immunoconjugates. Clin Cancer Res 15: 6052-6061, 2009
17. Cardillo TM, Govindan SV, Sharkey RM, et al: Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: Preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res 17:3157-3169, 2011
18. Govindan SV, Cardillo TM, Sharkey RM, et al: Milatuzumab-SN-38 conjugates for the treatment of CD74+ cancers. Mol Cancer Ther 12: 968-978, 2013
19. Cardillo TM, Govindan SV, Sharkey RM, et al: Sacituzumab govitecan (IMMU-132), an anti-Trop-2/SN-38 antibody-drug conjugate: Characterization and efficacy in pancreatic, gastric, and other cancers. Bioconjug Chem 26:919-931, 2015
20. Goldenberg DM, Cardillo TM, Govindan SV, et al: Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibodydrug conjugate (ADC). Oncotarget 6:22496-22512, 2015
21. Hajjar G, Sharkey RM, Burton J, et al: Phase I radioimmunotherapy trial with iodine-131-labeled humanized MN-14 anti-carcinoembryonic antigen monoclonal antibody in patients with metastatic gastrointestinal and colorectal cancer. Clin Colorectal Cancer 2:31-42, 2002
22. Sahlmann CO, Homayounfar K, Niessner M, et al: Repeated adjuvant anti-CEA radioimmunotherapy after resection of colorectal liver metastases: Safety, feasibility, and long-term efficacy results of a prospective phase 2 study. Cancer 123:638-649, 2017
23. Sharkey RM, Juweid M, Shevitz J, et al: Evaluation of a complementarity-determining regiongrafted (humanized) anti-carcinoembryonic antigen monoclonal antibody in preclinical and clinical studies. Cancer Res 55(23, Suppl)5935s-5945s, 1995
24. Gold P, Goldenberg NA: The carcinoembryonic antigen (CEA): Past, present, and future. McGill J Med 3:46-66, 1997
25. Gold P, Shuster J, Freedman SO: Carcinoembryonic antigen (CEA) in clinical medicine: Historical perspectives, pitfalls and projections.Cancer 42: 1399-1405, 1978
26. Govindan SV, Cardillo TM, Rossi EA, et al: Improving the therapeutic index in cancer therapy by using antibody-drug conjugates designed with a moderately cytotoxic drug. Mol Pharm 12:1836-1847, 2015
27. Cardillo TM, Sharkey RM, Govindan SV, et al: Superior SN-38 pharmacodynamic and tumoraccretion profiles of labetuzumab govitecan (IMMU-130) versus irinotecan in experimental human colonic cancer models. Proc Am Assoc Cancer Res 77:1042 , 2017 (abstr 4081)
28. Xie R, Mathijssen RH, Sparreboom A, et al: Clinical pharmacokinetics of irinotecan and its metabolites in relation with diarrhea. Clin Pharmacol Ther 72:265-275, 2002
29. Segal NH, Dotan E, Berlin JD, et al: Abstract CT211: IMMU-130, an SN-38 antibody-drug conjugate (ADC) targeting CEACAM5, is therapeutically active in metastatic colorectal cancer (mCRC): Initial clinical results of two Phase I studies. Cancer Res 74: CT211, 2014
30. Starodub AN, Ocean AJ, Shah MA, et al: Firstin-human trial of a novel anti-Trop-2 antibody-SN-38 conjugate, sacituzumab govitecan, for the treatment of diverse metastatic solid tumors. Clin Cancer Res 21:3870-3878, 2015
31. Eisenhauer EA, Therasse P, Bogaerts J, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228-247, 2009
32. Sharkey RM, McBride WJ, Cardillo TM, et al: Enhanced delivery of SN-38 to human tumor xenografts with an anti-Trop-2-SN-38 antibody conjugate (sacituzumab govitecan). Clin Cancer Res 21: 5131-5138, 2015
33. Beauchemin N, Draber P, Dveksler G, et al: Redefined nomenclature for members of the carcinoembryonic antigen family. Exp Cell Res 252: 243-249, 1999
34. Hammarström S: The carcinoembryonic antigen (CEA) family: Structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol 9:67-81, 1999
35. Grothey A, Van Cutsem E, Sobrero A, et al: Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381:303-312, 2013
36. Hirose K, Kozu C, Yamashita K, et al: Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene. Oncol Lett 3:694-698, 2012
37. Zhao H, Lee C, Sai P, et al: 20-Oacylcamptothecin derivatives: evidence for lactone stabilization. J Org Chem 65:4601-4606, 2000
38. Hanioka N, Ozawa S, Jinno H, et al: Human liver UDP-glucuronosyltransferase isoforms involved in the glucuronidation of 7-ethyl-10-hydroxycamptothecin. Xenobiotica 31:687-699, 2001
39. Pfizer: Camptosar-irinotecan hydrochloride injection, solution. Highlights of prescribing information. http://labeling.pfizer.com/ShowLabeling. aspx?id=533
40. Hoskins JM, Goldberg RM, Qu P, et al: UGT1A1-28 genotype and irinotecan-induced neutropenia: Dose matters. J Natl Cancer Inst 99:1290-1295, 2007
41. Garrett CR, Bekaii-Saab TS, Ryan T, et al: Randomized phase 2 study of pegylated SN-38 (EZN-2208) or irinotecan plus cetuximab in patients with advanced colorectal cancer. Cancer 119:4223-4230, 2013
42. Perez EA, Awada A, O'Shaughnessy J, et al: Etirinotecan pegol (NKTR-102) versus treatment of physician's choice in women with advanced breast cancer previously treated with an anthracycline, a taxane, and capecitabine (BEACON): A randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 16:1556-1568, 2015
43. Xie R, Mathijssen RH, Sparreboom A, et al: Clinical pharmacokinetics of irinotecan and its metabolites: A population analysis. J Clin Oncol 20: 3293-3301, 2002