A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors.
A phase I clinical trial was conducted to determine the clinical safety of Telomelysin, a human telomerase reverse transcriptase (hTERT) promoter driven modified oncolytic adenovirus, in patients with advanced solid tumors. A single intratumoral injection (IT) of Telomelysin was administered to three cohorts of patients (1 x 10(10), 1 x 10(11), 1 x 10(12) viral particles). Safety, response and pharmacodynamics were evaluated. Sixteen patients with a variety of solid tumors were enrolled. IT of Telomelysin was well tolerated at all dose levels. Common grade 1 and 2 toxicities included injection site reactions (pain, induration) and systemic reactions (fever, chills). hTERT expression was demonstrated at biopsy in 9 of 12 patients. Viral DNA was transiently detected in plasma in 13 of 16 patients. Viral DNA was detectable in four patients in plasma or sputum at day 7 and 14 post-treatment despite below detectable levels at 24 h, suggesting viral replication. One patient had a partial response of the injected malignant lesion. Seven patients fulfilled Response Evaluation Criteria in Solid Tumors (RECIST) definition for stable disease at day 56 after treatment. Telomelysin was well tolerated. Evidence of antitumor activity was suggested.
Nemunaitis
John
J
Mary Crowley Cancer Research Centers, Dallas, Texas, USA. jnemunaitis@marycrowley.org
Tong
Alex W
AW
Nemunaitis
Michael
M
Senzer
Neil
N
Phadke
Anagha P
AP
Bedell
Cynthia
C
Adams
Ned
N
Zhang
Yu-An
YA
Maples
Phillip B
PB
Chen
Salina
S
Pappen
Beena
B
Burke
James
J
Ichimaru
Daiju
D
Urata
Yasuo
Y
Fujiwara
Toshiyoshi
T
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000009:adverse effects / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D019098:Telomerase