KNOXVILLE, TN, -- Provectus (OTCQB: PVCT) today announced that updated safety and response results as well as preliminary treatment durability and immune response results from the Company's ongoing Phase 1b/2 study of PV-10 in combination with KEYTRUDA (pembrolizumab), an immune checkpoint inhibitor, were presented at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting, held in Chicago, IL from May 31-June 4, 2019. Intralesional injection of oncolytic immunotherapy PV-10 can yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells.1-5 PV-10 clinical development includes cutaneous melanoma and cancers of the liver, such as hepatocellular carcinoma, metastatic neuroendocrine tumors, and metastatic uveal melanoma, in both single-agent and combination therapy settings.
The Phase 1b portion of the study completed enrollment of 23 patients with advanced melanoma in April 2018 (NCT02557321). Patients with at least one injectable lesion and who were candidates for KEYTRUDA were eligible. Subjects received the combination treatment of PV-10 and KEYTRUDA every three weeks for up to five cycles (i.e., over a period of up to 12 weeks, with no further PV-10 administered after week 12), followed by only KEYTRUDA every three weeks for up to 24 months. The primary endpoint for the Phase 1b trial was safety and tolerability. Objective response rate (ORR) and progression-free survival (PFS) were key secondary endpoints (both assessed via RECIST 1.1 after five treatment cycles, and then every 12 weeks thereafter). Response follow-up of 6 patients (26%) still is ongoing.
Updated Results from the Presentation at ASCO:
The Company is enrolling and treating patients in an expansion cohort of up to 24 subjects to assess the PV-10-KEYTRUDA combination in patients who have failed to respond to initial treatment with checkpoint inhibition. Two patients in the Phase 1b study's main cohort were refractory to checkpoint inhibition: 1 achieved a CR after previously being on OPDIVO® for 12 months and 1 withdrew after previously being on YERVOY® for 3 years due to the onset of myasthenia gravis. Provectus plans to present preliminary data from this expansion cohort of refractory patients at a medical conference in the fourth calendar quarter of 2019.
Dominic Rodrigues, Vice Chair of the Company's Board of Directors, said, "These trial results demonstrate the safety profile, treatment response, durability of response, and immune response of the PV-10-checkpoint inhibition combination after minimal PV-10 intervention.7 Successful cancer combination therapy is achieved by pairing drugs that each show single-agent activity."
Mr. Rodrigues added, "Together with safety, response, biomarker, and quality of life data of single-agent PV-10 for the treatment of metastatic neuroendocrine tumors presented earlier today at ASCO, these advanced melanoma combination therapy data add to the abundance of drug activity information of PV-10 in both high and low mutation tumor types, and in both T cell and non-T cell inflamed tumor types."
A copy of the ASCO poster presentation is currently available on Provectus' website at https://www.provectusbio.com/media/docs/publications/PV-10-MM-1201_ASCO2019.pdf.
PV-10 causes acute oncolytic destruction of injected tumors, releasing damage associated molecular pattern molecules (DAMPs) and tumor antigens that initiate an immunologic cascade where local response by the innate immune system facilitates systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. T cell function can be further augmented by combining PV-10 with immune checkpoint inhibition.
PV-10 is undergoing clinical study for adult solid tumor cancers like melanoma and cancers of the liver (including metastatic symptomatic neuroendocrine tumors and metastatic uveal melanoma) and preclinical study for pediatric cancers like neuroblastoma5, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.
Orphan drug designation status has been granted to PV-10 by the U.S. Food and Drug Administration for the treatments of metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.
PV-10's active pharmaceutical ingredient is rose bengal disodium (RB) (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein disodium salt), a small molecule halogenated xanthene. PV-10 drug product is a bright rose red solution containing 10% w/v RB in 0.9% saline for injection, which is supplied in single-use glass vials containing 5 mL (to deliver) of solution and administered without dilution to solid tumors via intratumoral injection.
Provectus' intellectual property includes a family of US and international patents that protect the process by which pharmaceutical grade RB and related xanthenes are produced, reducing the formation of previously unknown transhalogenated impurities that exist in commercial grade RB in uncontrolled amounts. The requirement to identify and control these substances is in accordance with International Conference on Harmonisation (ICH) guidelines for the manufacturing of active pharmaceutical ingredient that is suitable for clinical trial and commercial pharmaceutical use. US patent numbers are 8,530,675, 9,273,022, and 9,422,260; patent expirations range from 2030 to 2031.
Provectus Biopharmaceuticals, Inc. (Provectus or the Company) is a clinical-stage biotechnology company developing a new class of drugs based on an entirely- and wholly-owned family of chemical small molecules called halogenated xanthenes. Information about the Company's clinical trials can be found at the NIH registry, www.clinicaltrials.gov. For additional information about Provectus, please visit the Company's website at www.provectusbio.com.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Kenilworth, New Jersey, U.S.A.
BAVENCIO® is a trademark of Merck KGaA, Darmstadt, Germany.
OPDIVO® and YERVOY® are registered trademarks of Bristol-Myers Squibb, New York, New York, U.S.A.
ERIVEDGE® is a registered trademark of Genentech, Inc., San Francisco, California, U.S.A.
FORWARD-LOOKING STATEMENTS: This release contains "forward-looking statements" as defined under U.S. federal securities laws. These statements reflect management's current knowledge, assumptions, beliefs, estimates, and expectations and express management's current views of future performance, results, and trends and may be identified by their use of terms such as "anticipate," "believe," "would," "could," "estimate," "expect," "intend," "may," "plan," "predict," "project," "will," and other similar terms. Forward-looking statements are subject to a number of risks and uncertainties that could cause our actual results to materially differ from those described in the forward-looking statements. Readers should not place undue reliance on forward-looking statements. Such statements are made as of the date hereof, and we undertake no obligation to update such statements after this date.
Risks and uncertainties that could cause our actual results to materially differ from those described in forward-looking statements include those discussed in our filings with the Securities and Exchange Commission (including those described in Item 1A of our Annual Report on Form 10-K for the year ended December 31, 2018).
Provectus Biopharmaceuticals, Inc.
Heather Raines, CPA
Chief Financial Officer