Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma.
OBJECTIVE
Treatment options for metastatic melanoma are limited. We conducted this phase II trial to assess the efficacy of JS1/34.5-/47-/granulocyte-macrophage colony-stimulating factor (GM-CSF) in stages IIIc and IV disease.


METHODS
Treatment involved intratumoral injection of up to 4 mL of 10(6) pfu/mL of JS1/34.5-/47-/GM-CSF followed 3 weeks later by up to 4 mL of 10(8) pfu/mL every 2 weeks for up to 24 treatments. Clinical activity (by RECIST [Response Evaluation Criteria in Solid Tumors]), survival, and safety parameters were monitored.


RESULTS
Fifty patients (stages IIIc, n = 10; IVM1a, n = 16; IVM1b, n = 4; IVM1c, n = 20) received a median of six injection sets; 74% of patients had received one or more nonsurgical prior therapies for active disease, including dacarbazine/temozolomide or interleukin-2 (IL-2). Adverse effects were limited primarily to transient flu-like symptoms. The overall response rate by RECIST was 26% (complete response [CR], n = 8; partial response [PR], n = 5), and regression of both injected and distant (including visceral) lesions occurred. Ninety-two percent of the responses had been maintained for 7 to 31 months. Ten additional patients had stable disease (SD) for greater than 3 months, and two additional patients had surgical CR. On an extension protocol, two patients subsequently achieved CR by 24 months (one previously PR, one previously SD), and one achieved surgical CR (previously PR). Overall survival was 58% at 1 year and 52% at 24 months.


CONCLUSIONS
The 26% response rate, with durability in both injected and uninjected lesions including visceral sites, together with the survival rates, are evidence of systemic effectiveness. This effectiveness, combined with a limited toxicity profile, warrants additional evaluation of JS1/34.5-/47-/GM-CSF in metastatic melanoma. A US Food and Drug Administration-approved phase III investigation is underway.
Senzer
Neil N
NN
Mary Crowley Cancer Research Centers, Dallas, TX 75201, USA. nsenzer@marycrowley.org
Kaufman
Howard L
HL
Amatruda
Thomas
T
Nemunaitis
Mike
M
Reid
Tony
T
Daniels
Gregory
G
Gonzalez
Rene
R
Glaspy
John
J
Whitman
Eric
E
Harrington
Kevin
K
Goldsweig
Howard
H
Marshall
Tracey
T
Love
Colin
C
Coffin
Robert
R
Nemunaitis
John J
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D018259:Herpesvirus 1, Human; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D008545:Melanoma / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D050130:Oncolytic Virotherapy / Q000009:adverse effects; D012878:Skin Neoplasms / Q000473:pathology*
D016178:Granulocyte-Macrophage Colony-Stimulating Factor