Study of T Cell Mediated Immunity from Combination of PV-10 and Immune Checkpoint Blockade in Murine Melanoma Models Published in PLOS ONE

Monday April 30, 2018
  • Combinations with PV-10 included + anti-CTLA-4; + anti-PD-1; + anti-PD-L1; and, + anti-PD-1 + Treg depletion
  • Data provided basis for ongoing Phase 1b/2 study of PV-10 in combination with KEYTRUDA® for Stage IV melanoma (NCT02557321)

KNOXVILLE, TN, /GLOBE NEWSWIRE/ -- Provectus Biopharmaceuticals, Inc. (OTCQB: PVCT, www.provectusbio.com), ("Provectus" or the "Company"), a clinical-stage biotechnology company developing PV-10 as the first small molecule oncolytic immunotherapy for solid tumor cancers, today announced that the open-access journal PLOS ONE published results from an H. Lee Moffitt Cancer Center and Research Institute ("Moffitt") study investigating cancer combination therapy with intralesional ("IL") PV-10 and immune checkpoint blockade (anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies) in murine melanoma models.1,2 The authors also examined the role of specific immune cell populations in eliciting and controlling tumor-specific response.

This article may be accessed via PLOS ONE's website at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196033.

The Moffitt authors noted, "In this study, we have shown the impact of combining systemic checkpoint blockade (PD-1, PD-L1) with the tumor-specific immune response induced by IL PV-10. Treatment with IL PV-10 and anti-PD-1 antibody resulted in a delay in tumor growth and enhanced T cell activation in the M05 tumor model. Similar effects were observed with IL PV-10 and anti-PD-L1 antibody in the B16 tumor model. The effect of combination therapy with IL PV-10 and PD-1 blockade is mediated by CD8+ T cells, and depletion of either CD4+ T cells or CD4+CD25+ Tregs enhances anti-tumor immunity in the M05 melanoma model. Together these results support further development of clinical trials to assess safety and anti-tumor T cell responses in patients after IL injection of PV-10 in combination with checkpoint blockade."

Dominic Rodrigues, Vice Chair of the Company's Board of Directors, said, "We are grateful to our research collaborators, like those at Moffitt, who continue to independently establish PV-10 as an oncolytic immunotherapy in both monotherapy and combination therapy settings."

Mr. Rodrigues added, "This PLOS ONE work established the rational clinical foundation for our ongoing Phase 1b/2 study PV-10 in combination with anti-PD-1 drug KEYTRUDA for patients with Stage IV melanoma. Moffit's work also builds on the foundation for future combinations of PV-10 and anti-PD-L1 agents as well as other potential combinations and permutations of cancer therapies that include PV-10 as a key element."

About our Phase 1b/2 Study of PV-10 + KEYTRUDA for Stage IV Melanoma

The Phase 1b portion of the study continues to enroll patients with metastatic melanoma at clinical sites in the U.S. (NCT02557321). Stage IV patients with at least one injectable lesion who are candidates for KEYTRUDA are eligible. A total of up to 24 patients would receive the combination of IL PV-10 and KEYTRUDA every three weeks for five cycles (i.e., for 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 is safety and tolerability; objective response rate and progression-free survival are key secondary endpoints (both assessed via RECIST 1.1 after five treatment cycles, and then every 12 weeks thereafter).

About PV-10

Provectus' lead investigational oncology drug product, PV-10, the first small molecule oncolytic immunotherapy, can induce immunogenic cell death. PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver, and preclinical study for pediatric cancers.

About Provectus

Provectus is a clinical-stage biotechnology company leading the development of a new class of drugs based on 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.

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, 2017).

References:

1. The Society for Immunotherapy of Cancer (SITC) 29th Annual Meeting & Associated Programs (SITC 2014): Pilon-Thomas et al., Efficacy of intralesional injection with PV-10 in combination with co-inhibitory blockade in a murine model of melanoma. J Immunother Cancer. 2014; 2(Suppl 3): P120. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288419/. Accessed April 16, 2018. (Poster).

2. The American Association for Cancer Research (AACR) Annual Meeting 2016: Weber et al., T cell mediated immunity after combination therapy with intralesional PV-10 and co-inhibitory blockade in a melanoma model. Cancer Res. July 15 2016 (76) (14 Supplement) 4978. http://cancerres.aacrjournals.org/content/76/14_Supplement/4978. Accessed April 16, 2018.

Trademark

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Kenilworth, New Jersey, U.S.A.

Contact:

Provectus Biopharmaceuticals, Inc.
Tim Scott, Ph.D.
President
Phone: 866-594-5999

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