NEW YORK — Recruitment will begin soon for a phase 3 trial that will compare intralesional PV-10 with chemotherapy in patients with stage IIIb or IIIc melanoma, according to a presenter at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.
The analysis will include 225 patients. Two-thirds will be randomly assigned to monthly injections with PV-10 (Provectus), a sterile, non-pyrogenic solution of rose bengal disodium that destroys tumors by necrosis. The other patients will be assigned standard-dose chemotherapy with dacarbazine or temozolomide.
All patients must have cutaneous and subcutaneous disease with no active nodal disease, and all lesions must be BRAF wild type. All patients must be either refractory to or not candidates for systemic immunotherapy.
Sanjiv S. Agarwala
“This is a trial design that is difficult to do,” Sanjiv S. Agarwala, MD, chief of oncology and hematology at St. Luke’s Cancer Center, professor at Temple University School of Medicine and a HemOnc Today Editorial Board member, said during a presentation. “We’re going to need a lot of centers, and there will be smaller groups per center because these are not easy patients to find. But we’re not going to deprive patients of the ability to get checkpoint inhibitors if that is the right treatment for them.”
Chemotherapy is a reasonable comparator because few other treatment options exist post-checkpoint inhibitors, Agarwala said.
Patients assigned to chemotherapy will have the option to cross over to PV-10.
PFS will serve as the primary endpoint, and secondary endpoints will include complete response rate, duration of complete response, OS and safety.
“In clinical trial development, we have to make a trial that is fair to the drug and also fair to the patients,” Agarwala said. “I think this trial fits this design.”
PV-10 — a chemoablative agent — is not metabolized, has a short half-life and is excreted via bile.
Tests in animal models suggest the agent could be effective in various tumor types; however, most available data on PV-10 relates to its use in melanoma.
A phase 2 trial conducted between October 2007 and May 2010 included 80 patients with stage III or stage IV disease. Sixty percent of patients were men, and 51% were aged 70 years or older.
More than one-third of patients (36%) had 10 or more lesions. Patients in the cohort had a median 6.3 cm sum diameter of study lesions and were refractory to a median of six prior interventions, the most common of which were excision (100%), nodal biopsy (63%), regional chemotherapy (24%), immunotherapy (21%) and radiotherapy (21%).
Researchers reported a complete response rate of 26% (95% CI, 17-37) and an overall response rate of 51% (95% CI, 40-63). Median time to response was 1.9 months, and responses were durable, Agarwala said. Eighteen percent of patients achieved stable disease.
Fifty-six percent of lesions achieved complete response after one or two monthly injections.
“We observed the highest response rate in patients in whom we injected all lesions, so that is the reason why in the phase 3 trial we will select patients for whom we can inject every lesion,” Agarwala said.
Toxicities were primarily limited to the injection site, with the most systemic problem being photosensitivity, Agarwala said.
Although the phase 3 trial is just getting underway, combination studies in patients with stage IV melanoma are planned.
“Even though we are going to test PV-10 as a single-agent treatment, I firmly believe the future of these intralesional agents is in combination,” Agarwala said. – by Mark Leiser
Agarwala SS. Intralesional PV-10. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; April 10-11, 2015; New York.
Disclosure: Agarwala reports no relevant financial disclosures.