PV-10: study shows 50% of cutaneous melanoma patients achieve complete response

In patients with locally advanced cutaneous melanoma who had all their lesions injected with the investigational agent PV-10 half achieved a complete response, reported a study presented at American Society of Clinical Oncology meeting, held in Chicago, Illinois, May 30 to June 2.

PV-10, a 10 % solution of Rose Bengal originally used as an agent to stain necrotic tissue in the cornea, has been designed for injection into solid tumors (intralesional administration), thereby reducing the potential for systemic side effects.

In the open label phase 2 study between October 2007 and May 2010, 80 patients with locally advanced cutaneous disease refractory to a median of six previous interventions, were recruited from seven centres in the USA and Australia to receive up to four treatment cycles of intralesional (IL) PV-10 injections. Furthermore, up to two ‘bystander’ lesions were identified that underwent biopsy to confirm melanoma, but did not receive treatment. The current abstract, presented at ASCO by Sanjiv Agarwala, from St Luke’s Hospital and Health Network, Bethlehem, Pennsylvania, explored the subgroup of patients who had all or most of their lesions injected, leaving out those with more advanced disease where substantial numbers of lesions went untreated.

Results show that for the 28 patients who had all their existing melanoma lesions injected with PV-10, the overall response rate was 71% (CI 51-87%) with 50% achieving a complete response (CI 31-69%). Furthermore, when the 28 patients who had all their lesions injected were analysed together with 26 patients who had one or two lesions left untreated (to investigate bystander effects) a complete response was achieved in 232 of the 363 injected lesions (64%). The study showed that in the combined analysis 121 lesions required a single injection for complete response, 84 required two injections, 22 required three injections and five required four injections.

“These sub-group analyses show that response to PV-10 is maximized when all lesions get treated. The level of response observed in this heavily pre treated or refractory patient population with locally advanced cutaneous melanoma is noteworthy since, unlike those with more advanced disease, these patients have limited treatment options now or on the horizon,” said Eric Wachter, the Chief Technology Officer at Provectus, who co-developed PV-10.

That 56% of lesions only required one or two injections to achieve a complete response, he added, underlines the simplicity of PV-10 treatment.

In a second pilot clinical trial, also presented as an abstract at ASCO, Amod Sarnaik and colleagues, from Moffitt Cancer Center Tampa, Florida, showed that following IL PV-10 injection post treatment biopsies of both PV-10-injected and uninjected study lesions led to pathologic complete response (pCR) in four of the eight patients and that all eight patients exhibited at least partial regression of injected lesions. One to two weeks after injection significant increases were detected in peripheral blood T-cells, including CD8+ (p=0.03), CD4+ (p=0.06), CD3+ (p=0.03), and NKT (p=0.05). Six of eight patients had metastatic disease refractory to previous ipilimumab, anti PD-1 and/or vemurabenib therapy.

“This data provides more and more evidence that you are altering both local and systemic immunity in a positive way,” said Jeffrey Weber, the senior author, from Moffitt Cancer Center. “It also provides a rationale for combination trials of PV-10 with check point protein inhibitors, such as ipilimumab, pembrolizumab and nivolumab. PV-10 might offer the perfect way to prime the immune system.”

Following the presentation Provectus announced that a phase 3 trial of PV-10 to generate sufficient data for a new drug application (NDA) is expected to start accrual in the second half of 2014. The study endpoints include progression free survival (by RECIST 1.1), complete response rate (by RECIST 1.1), and overall survival. The expanded access or compassionate use sites currently offering PV-10 to patients in the US and Australia, Provectus believes, can be used to expedite early recruitment.

References

Sanjiv S. Agarwala. “Efficacy of intralesional rose bengal in patients receiving injection in all existing melanoma in phase II study PV-10-MM-02.” ASCO 2014, J Clin Oncol 32:5s, 2014 (suppl; abstr 9027).

Amod Sarnaik. "Assessment of immune and clinical efficacy after intralesional PV-10 in injected and uninjected metastatic melanoma lesions." ASCO 2014, J Clin Oncol 32:5s, 2014 (suppl; abstr 9028).