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


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).


CONCLUSIONS
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.
Chung
Ki Y
KY
Gastrointestinal Medical Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. chungk@mskcc.org
Gore
Ira
I
Fong
Lawrence
L
Venook
Alan
A
Beck
Stephen B
SB
Dorazio
Prudence
P
Criscitiello
Peggy J
PJ
Healey
Diane I
DI
Huang
Bo
B
Gomez-Navarro
Jesus
J
Saltz
Leonard B
LB
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology; D060908:CTLA-4 Antigen; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C520704:tremelimumab