Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer Journal Article

  

Authors:	Chung, K. Y.; Gore, I.; Fong, L.; Venook, A.; Beck, S. B.; Dorazio, P.; Criscitiello, P. J.; Healey, D. I.; Huang, B.; Gomez-Navarro, J.; Saltz, L. B.
Article Title:	Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer
Abstract:	Purpose Safety and efficacy of tremelimumab (CP-675,206), a fully human anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) monoclonal antibody, were assessed in patients with treatment-refractory colorectal cancer. Patients and Methods A single-arm, multicenter, phase II trial was conducted in patients with Eastern Cooperative Oncology Group performance status <= 1 and measurable colorectal carcinoma for whom standard treatments for metastatic disease had failed. Patients received 15 mg/kg tremelimumab intravenously every 90 days until progression. Primary end point was objective response status (per Response Evaluation Criteria in Solid Tumors). Secondary end points included safety, duration of response, progression-free survival, and overall survival. Results Forty-seven patients who had received extensive prior therapies (all had received fluoropyrimidines, oxaliplatin, and irinotecan; most [91%] had also received cetuximab) were treated. Grade 3/4 treatment-related adverse events (AEs) were diarrhea (n = 5; 11%), ulcerative colitis (n = 1; 2%), fatigue (n = 1; 2%), autoimmune thrombocytopenia (n = 1; 2%), and hypokalemia (n = 1; 2%), which resolved spontaneously or with interventions. Six patients discontinued because of an AE; two were considered treatment related. Of 45 response-evaluable patients, 44 did not reach second dose (43 progressive disease; one discontinuation). Twenty-one patients (45%) lived >= 180 days after enrollment. One patient (2%; 90% CI, < 1% to 10%) had a stable pelvic mass and substantial regression in an adrenal mass (partial response). This patient received five tremelimumab doses; response duration was 6 months (enrollment to disease progression, 15 months). Conclusion Tremelimumab did not demonstrate clinically meaningful single-agent activity in this patient population, although the number of survivors at 6 months and the one patient with confirmed partial response are potentially interesting. Further study of tremelimumab in combination with other agents may be warranted.
Keywords:	melanoma; immunity; trial; antitumor-activity; blockade; cp-675,206
Journal Title:	Journal of Clinical Oncology
Volume:	28
Issue:	21
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Date Published:	2010-07-20
Start Page:	3485
End Page:	3490
Language:	English
ACCESSION:	ISI:000280003700014
DOI:	10.1200/jco.2010.28.3994
PROVIDER:	wos
PUBMED:	20498386
Notes:	--- - Article - "Source: Wos"

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