PMID- 19139427
OWN - NLM
STAT- MEDLINE
DCOM- 20090318
LR  - 20220316
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 27
IP  - 7
DP  - 2009 Mar 1
TI  - Phase I/II trial of tremelimumab in patients with metastatic melanoma.
PG  - 1075-81
LID - 10.1200/JCO.2008.19.2435 [doi]
AB  - PURPOSE: Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with 
      tremelimumab (CP-675,206), a fully human anti-CTLA4 monoclonal antibody, was 
      tolerated and demonstrated antitumor activity in a single dose, dose-escalation 
      phase I trial in patients with solid tumors. This phase I/II trial was conducted 
      to examine safety of multiple doses of tremelimumab, to further assess efficacy, 
      and to identify an appropriate dosing regimen for further development. PATIENTS 
      AND METHODS: Twenty-eight patients with metastatic melanoma received monthly 
      intravenous infusions of tremelimumab at 3, 6, or 10 mg/kg for up to 1 year to 
      determine recommended monthly phase II dose. During phase II, 89 patients 
      received tremelimumab 10 mg/kg once every month or 15 mg/kg every 3 months. 
      RESULTS: No dose-limiting toxicity was observed in phase I once every month 
      dosing. In phase II, 8 (10%) of 84 response-assessable patients attained 
      objective antitumor responses; best overall objective response was one complete 
      response and three partial responses in each dosing regimen. Most responses were 
      durable (range, 3 to 30+ months). Most frequent treatment-related adverse events 
      (AEs) were diarrhea, rash, and pruritus. Frequency of grade 3/4 AEs was 13% in 
      the 15 mg/kg every 3 months arm and 27% in the 10 mg/kg once every month. Serious 
      AEs were also less frequent in the 15 mg/kg once every 3 months cohort (9% v 23% 
      in 10 mg/kg arm). CONCLUSION: Multiple infusions of tremelimumab were generally 
      tolerable and demonstrated single-agent antitumor activity. Both phase II 
      regimens generated durable tumor responses. Based on its more favorable safety 
      profile, 15 mg/kg every 3 months was selected for further clinical testing.
FAU - Camacho, Luis H
AU  - Camacho LH
AD  - Oncology Consultants, Department of Research, 920 Frostwood, Ste 780, Houston, TX 
      77024, USA. lcamacho@oncologyconsultants.com
FAU - Antonia, Scott
AU  - Antonia S
FAU - Sosman, Jeffrey
AU  - Sosman J
FAU - Kirkwood, John M
AU  - Kirkwood JM
FAU - Gajewski, Thomas F
AU  - Gajewski TF
FAU - Redman, Bruce
AU  - Redman B
FAU - Pavlov, Dmitri
AU  - Pavlov D
FAU - Bulanhagui, Cecile
AU  - Bulanhagui C
FAU - Bozon, Viviana A
AU  - Bozon VA
FAU - Gomez-Navarro, Jesus
AU  - Gomez-Navarro J
FAU - Ribas, Antoni
AU  - Ribas A
LA  - eng
GR  - K24 CA128953/CA/NCI NIH HHS/United States
GR  - CA 37517/CA/NCI NIH HHS/United States
GR  - CA 27469/CA/NCI NIH HHS/United States
GR  - CA 87558/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20090112
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - QEN1X95CIX (tremelimumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug-Related Side Effects and Adverse Reactions
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Melanoma/*drug therapy/*secondary
MH  - Middle Aged
MH  - Survival Analysis
EDAT- 2009/01/14 09:00
MHDA- 2009/03/19 09:00
CRDT- 2009/01/14 09:00
PHST- 2009/01/14 09:00 [entrez]
PHST- 2009/01/14 09:00 [pubmed]
PHST- 2009/03/19 09:00 [medline]
AID - JCO.2008.19.2435 [pii]
AID - 10.1200/JCO.2008.19.2435 [doi]
PST - ppublish
SO  - J Clin Oncol. 2009 Mar 1;27(7):1075-81. doi: 10.1200/JCO.2008.19.2435. Epub 2009 
      Jan 12.