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 <or= 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 >or= 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.

• Authors: Ki Y Chung, Ira Gore, Lawrence Fong, Alan Venook, Stephen B Beck, Prudence Dorazio, Peggy J Criscitiello, Diane I Healey, Bo Huang, Jesus Gomez-Navarro, Leonard B Saltz
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 21 Pg. 3485-90 (Jul 20 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20498386 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antigens, CD
• CTLA-4 Antigen
• CTLA4 protein, human
• tremelimumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antigens, CD (immunology)
• CTLA-4 Antigen
• Colorectal Neoplasms (drug therapy, mortality)
• Female
• Humans
• Male
• Middle Aged