Clinical Trials

Date: 2016-03-19

Type of information: update on patient enrollment

phase: 3

Announcement: update

Company: Provectus Pharmaceuticals (USA - TN)

Product: PV-10 and pembrolizumab

Action mechanism:

• monoclonal antibody/immune checkpoint inhibitor. Keytruda® (pembrolizumab - MK-3475) is an investigational, highly selective monoclonal anti-PD-1 antibody designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system. MK-3475 is currently being studied in three clinical trials for advanced melanoma including a Phase III trial of MK-3475 versus ipilimumab in ipilimumab-naïve advanced melanoma patients (PN 006). Enrollment is complete in the advanced melanoma cohorts in the company’s Phase IB trial (PN 001) and the Phase II trial (PN 002) comparing two doses of MK-3475 versus chemotherapy in patients with advanced melanoma who have progressed after prior therapy. Pembrolizumab is being evaluated across more than 30 types of cancers, as monotherapy and in combination. It is anticipated that by the end of 2014, the pembrolizumab development program will grow to more than 24 clinical trials, enrolling an estimated 6,000 patients at nearly 300 clinical trial sites worldwide. In April 2013, MK-3475 has received a Breakthrough Therapy designation for advanced melanoma from the FDA. Keytruda® is the first approved drug that blocks the PD-1 cellular pathway.
• PV-10 is an investigational new drug containing a proprietary injectable formulation of rose bengal disodium, a water-soluble xanthene dye currently in use in a topical opthalmic diagnostic. PV-10 is designed for injection into solid tumors (intralesional administration).

Disease: Stage III locally advanced cutaneous melanoma

Therapeutic area: Cancer - Oncology

Country: Australia, USA

Trial details:

• The Phase 3 study is an international multicenter, open-label, randomized controlled trial (RCT) of single-agent intralesional (IL) PV-10 versus systemic chemotherapy to assess treatment of locally advanced cutaneous melanoma in patients who are BRAF V600 wild-type and have failed or are not otherwise candidates for ipilimumab or another immune checkpoint inhibitor. Subjects in the PV-10 arm receive IL PV-10 to all of their melanoma lesions. Subjects in the comparator arm receive the investigator's choice of dacarbazine or temozolomide as determined by investigator preference and/or local availability of the agent. Effectiveness will be assessed by comparison of progression-free survival (PFS) between all intent-to-treat (ITT) subjects in the two study arms. The primary outcome measure of PFS is assessed every 12 weeks up to 18 months using RECIST 1.1 criteria. Secondary outcome measures include complete response rate (CRR) and its duration (assessed every 12 weeks up to 18 months); and overall survival (OS) assessed every 12 weeks up to 18 months. Safety and tolerability will be assessed by monitoring the frequency, duration, severity and attribution of adverse events and evaluating changes in laboratory values and vital signs. (NCT02288897 )

Latest news:

• • On March 16, 2016, Provectus Biopharmaceuticals announced that the protocol for its phase 3 clinical trial for PV-10 as an investigational treatment for melanoma has been amended to reflect current and evolving standards of care and applicable patient population for a global study in melanoma. Major amendments to the protocol include the addition of talimogene laherparepvec (Imlygic™) as an option for use as comparator. The amended protocol also extends eligibility to include Stage IV M1a patients having no active nodal or distant cutaneous or subcutaneous metastatic disease. These patients have disease characteristics and prognosis similar to that of the Stage IIIB and IIIC patients that initially defined the study patient population. In addition, the updated protocol clarifies eligibility for patients not having access to immune checkpoint inhibitors due to standard of care and those not having access to targeted therapy due to standard of care, as well as inclusion of patients who have failed targeted therapy. In the latter case, patients who have failed targeted therapy but meet study eligibility criteria have similar disease manifestations to the remaining study population but have limited treatment options. Dr. Eric Wachter, CTO of Provectus, said, "These kinds of amendments are commonplace in phase 3 studies and serve to fine-tune the patient population and study procedures to match changing care standards for a large global study. They are the direct result of current and emerging options for these patients and have been developed with extensive input from global leading melanoma investigators. In particular, the most obvious amendment addresses approval in late October of Imlygic by the FDA as the first and only oncolytic viral therapy. As we implement the amended protocol we will assess potential impact on study timelines."
• • On January 12, 2016, Provectus Biopharmaceuticals confirmed that patients have been dosed in its Phase 3 clinical trial of PV-10, Provectus' novel investigational drug for cancer, for Stage III locally advanced cutaneous melanoma.  Currently, three sites are recruiting patients, with four additional sites nearing opening of enrollment. Additional sites are in process of being added in the coming weeks. (St. Luke's Hospital and Health Network, Easton, PA;Atlantic Health System, Morristown, NJ;  University of Louisville, Louisville, KY; Huntsman Cancer Institute, Salt Lake City, UT; (not yet recruiting), M.D. Anderson Cancer Center, Houston, TX; (not yet recruiting), Sharp Memorial Hospital, San Diego, CA; (not yet recruiting), Princess Alexandra Hospital, Brisbane, Australia; (not yet recruiting).

Is general: Yes