Complete Response Rates Seen in Refractory Melanoma Patients

(Knoxville, TN, USA), a development-stage oncology and dermatology biopharmaceutical company, reported that data on its investigational agent PV-10 for intralesional (IL) treatment of locally advanced cutaneous melanoma was featured in two presentations, on June 2, 2014, during the American Society of Clinical Oncology (ASCO) annual meeting held in Chicago (IL USA). These presentations show that IL PV-10 can potentially offer cancer patients control of their cutaneous symptoms and provoke a systemic antitumor immune response that may lead to response of uninjected lesions (the “bystander effect” that has been observed in earlier clinical studies of PV-10).

The first highlighted poster, presented by Sanjiv S. Agarwala, MD, of the St. Luke’s Cancer Center (Bethlehem, PA, USA), was entitled “Efficacy of intralesional rose bengal in patients receiving injection in all existing melanoma in phase II study PV-10-MM-02.” The second highlighted poster, presented by Amod Sarnaik, MD, from Moffitt Cancer Center (Tampa, FL, USA) was titled “Assessment of immune and clinical efficacy after intralesional PV-10 in injected and uninjected metastatic melanoma lesions.”

Dr. Agarwala and coauthors from seven prominent melanoma centers in the United States and Australia studied the safety and efficacy of IL PV-10 in an 80-patient international, multicenter, single arm phase 2 trial. A subgroup analysis of 28 patients with all existing melanoma lesions injected and an additional 26 patients with only one to two uninjected bystander lesions showed that these patients experienced an exceptionally high rate of response. The best overall response rate (BORR) in the 28-patient “all treated” subgroup was 71% (confidence interval (CI) of 51%–87%), with 50% complete response (CI 31%–69%). Among the 54 patients in both of these subgroups (i.e., patients who had all of their disease monitored in the study), complete response (CR) was achieved in 232 of 363 injected lesions (64% CR). Furthermore, CR was achieved in 121 lesions after a single injection of PV-10; 84 lesions required two injections to achieve CR; 22 lesions required three injections; and five lesions required all four allowed four injections.

Dr. Agarwala said, “The high rate of symptom control in refractory patients with disease limited to the skin, manifested in CR of all monitored disease after minimal intervention, is the basis for a pending breakthrough therapy designation application for PV-10. Although the primary ablative effect is responsible for CR in injected lesions, durability of response and bystander response observed in this study implicate an immunologic mechanism of action secondary to ablation.”

In the Moffitt poster, Dr. Sarnaik and coauthors reported interim results of a pilot clinical trial designed to investigate the immunologic basis of this bystander response. In this single institution translational study, a target lesion and a bystander were biopsied prior to treatment of the target lesion with PV-10. Both lesions were then resected within 7-14 days of target lesion injection and compared to pre-treatment biopsies. Peripheral blood was also collected pretreatment, at the time of resection, and at day 28. The researchers note “treatment with IL PV-10 led to pCR (pathologic complete response) in the post-treatment biopsies of both PV-10 injected and uninjected study lesions in four of the eight patients, and all eight exhibited at least partial regression of the injected lesion.” The abstract continues, “Six of the eight patients had metastatic disease refractory to previous ipilimumab, anti-PD-1 and/or vemurafenib therapy.” Based on T cells isolated from the peripheral blood of the patients, the authors conclude that, “IL PV-10 treatment can lead to systemic antimelanoma immunity and pCR in injected and uninjected lesions including treatment-refractory tumors.”

Craig Dees, PhD, CEO of Provectus, said, “Taken together, these posters indicate that, with minimal intervention, PV-10 can rapidly eliminate refractory cutaneous melanoma lesions. IL PV-10 is also associated with an increase in important circulating immune cells specific to the injected lesion, potentially explaining the high rate of bystander lesion regression seen in our clinical trials of PV-10 in locally advanced melanoma patients. The duration of response and the bystander response reported in the phase 2 trial was beyond the scope of simple tumor ablation. In 2013, Moffitt researchers published data from mice showing increased antitumor T cell responses, and this year at ASCO they have bridged that nonclinical finding to the same phenomenon in man. It is unprecedented for a small molecule ablative agent to have this kind of immune system activity detectable in peripheral blood of patients. The one-two punch from PV-10 [rapidly reducing tumor burden and producing immune system stimulation] is presumably the underlying driver of these durable complete responses in patients with cutaneous melanoma.”

Provectus submitted an application in March 2014 to the US Food and Drug Administration (FDA) for breakthrough therapy designation for PV-10 based on the results from its phase 2 clinical study related to metastatic melanoma and is researching efficacy of PV-10 for other indications, including liver and breast cancers.

Provectus Biopharmaceuticals specializes in developing oncology and dermatology therapies. Its novel oncology drug PV-10, (a formulation of the small molecule ablative agent rose bengal disodium) is designed to selectively target and destroy cancer cells without harming surrounding healthy tissue, significantly reducing potential for systemic side effects. Its oncology focus is on melanoma, breast cancer and cancers of the liver. The company has received orphan drug designations from the FDA for its melanoma and hepatocellular carcinoma indications. Its dermatological drug PH-10 also targets abnormal or diseased cells, with the current focus on psoriasis and atopic dermatitis. Provectus has recently completed phase 2 trials of PV-10 as a therapy for metastatic melanoma, and of PH-10 as a topical treatment for atopic dermatitis and psoriasis.

Provectus Biopharmaceuticals
St. Luke’s Cancer Center
Moffitt Cancer Center

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