A Phase I/II, Open-Label Study of JX-594 (Thymidine Kinase-deleted Vaccinia Virus Plus GM-CSF) Administered by Intratumoral Injection in Patients With Unresectable Stage 3 or Stage 4 Malignant Melanoma
Cancer of the skin is the most common of all cancers, probably accounting for more than 50%
of all cancers. Melanoma accounts for about 4% of skin cancer cases but causes a large
majority of skin cancer deaths. The American Cancer Society estimates that about 62,190 new
melanomas will be diagnosed in the United States during 2006.
DTIC is the only chemotherapy drug approved by the FDA for the treatment of metastatic
melanoma. The reported response rates are 5-20% without any evidence of prolonged survival
in randomized clinical trials versus best supportive care. The median overall survival for
melanoma patients treated with DTIC alone is approximately 8 months; PFS and TTP following
treatment with DTIC is approximately 7 weeks, and the objective response rate for DTIC alone
(CR+PR) is less than 10% (Millward, 2004). Other chemotherapy agents including cisplatin
and carboplatin, BCNU, vindesine, paclitaxel, docetaxel, and vinorelbine have also been
tested but none have improved upon the very modest activity of DTIC.
Melanoma may be the optimal target for JX-594 immunotherapy because of the relatively high
rate of accessible disease for injection, the positive response of melanoma seen with IL-2
immunotherapy, and the lack of effective, tolerable therapy for patient with metastatic
melanoma. Furthermore, it is speculated that JX-594 replication targets the EGFR pathway,
which is highly expressed in melanocytes.
Results from an initial Phase I/II study suggest that intratumoral injection of JX-594 is
safe and effective in treating both injected and distant disease in patients with surgically
incurable metastatic melanoma. Response of both injected tumors (in 5 of 7 patients) and
response of at least one non-injected tumor (in 4 of 7 patients) was demonstrated, including
two patients who achieved a partial response (6 + months) and a complete response (4 +
months) to JX-594 treatment. Particularly noteworthy is that efficacy and gene expression
occurred despite pre-treatment vaccination (and, therefore, pre-existing anti-vaccinia
immunity) in all patients.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate for injected tumor(s)
Initial response assessment at 6 weeks
James Burke, M.D.
United States: Food and Drug Administration
|UCLA||Los Angeles, California 90095|
|Cancer Center of the Carolinas||Greenville, South Carolina 29615|
|Billings Clinic||Billings, Montana 59107-7000|