This article is more than 5 years old. Information may no longer be current.
IL-12 plasmid electroporation appears effective in metastatic melanoma
Click Here to Manage Email Alerts
NEW YORK — Electroporation with interleukin-12 plasmid was associated with positive durable response rates and a tolerable adverse effect profile in patients with metastatic melanoma, according to a presenter at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.
Efforts to deliver genes to tumors have been challenging because cells are covered by thin but impermeable membranes.
Adil Daud
“When you’re trying to get something like that in, you either need to use a virus or something to disrupt the membrane,” Adil Daud, MD, MBBS, a clinical professor of medicine and dermatology at the University of California, San Francisco, said during a presentation. “If you were to apply a [direct] current, some pores are opened in the cell membrane and that will force DNA molecules, like plasmids, to enter. The pores are transient — they just last a few thousandths of a second before the cell reseals and heals — but now you have a plasmid inside a cell.”
Researchers began using that approach several years ago to test cytokines and immunologically active substances in tumor treatment.
A first-in-humans phase 1 trial conducted from 2005 to 2007 demonstrated electroporation with interleukin-12 plasmid (pIL-12) is safe and nontoxic in patients with melanoma.
Daud and colleagues designed a phase 2 trial to evaluate the efficacy of pIL-12 electroporation in 25 patients with stage III unresectable or stage IV disease.
All patients had in-transit, cutaneous or subcutaneous metastasis, as well as tumors >1 mm. No patients had extensive visceral disease. Patients received 0.5 mg/mL pIL-12 intratumorally with electroporation on days 1, 5 and 8. Patients were able to be re-treated every 3 months if there was no evidence of systemic progression.
Distant complete response rate at 24 weeks served as the primary endpoint. Local response rate, objective PFS and OS served as secondary endpoints.
Accrual is almost complete, and Daud presented data on the first 13 patients included in an interim analysis.
At 3 months, researchers observed durable response in 69% of patients and 68% of treated lesions. At 6 months, they observed durable response in 38% of patients and 45% of treated lesions.
The interim analysis showed 31 lesions demonstrated overall response at day 39. Of those 31 lesions, 21 (67.7%) continued to demonstrate durable response at 3 months and 14 (45.1%) continued to demonstrate durable response at 6 months.
By day 180, two of 13 patients with evaluable distant disease demonstrated distant response. Four patients had not yet reached day 180, six had progressive disease and one patient had withdrawn from the study.
“We are waiting to see how durable these responses are going to be,” Daud said. “Our last patient probably will be treated in April, so we should have some more on this trial shortly.”
The adverse event profile was relatively mild compared with other types of treatments, he said. The investigators reported 18 treatment-related adverse events, including grade 2 fatigue, erythema and maculopapular rash.
“There’s incredible excitement with local therapies,” Daud said. “They are nontoxic, and one of the advantages they have over vaccination, in general, is when you do vaccination, you can actually divert the immune response to the vaccine site. … By injecting antigens or immune stimulants directly into the tumor, you may avoid that problem. It’s an old idea, but maybe the time has come to explore this more in-depth.”
For more information:
Daud A. Electro-gene therapy with IL-12 plasmid in metastatic melanoma. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; March 22-23, 2013; New York.
Disclosure: Daud reports advisory board roles with Amgen and OncoSec, and research funding from Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck, OncoSec and Pfizer.
Perspective
Back to Top
Joseph R. Bertino, MD
This is an interesting approach, but this is local therapy. The problem with melanoma is metastasis, some of which cannot be treated locally. The key to the success of this treatment would be regression of nontreated lesions, as well.
Click Here to Manage Email Alerts