Provectus Announces Preliminary Results from Phase 1 Trial of PV-10 for Treatment of Metastatic Neuroendocrine Tumors at ASCO 2019

Monday June 3, 2019
  • - No safety concerns identified
  • - 50% ORR and 83% disease control of injected lesions
  • - Stable Chromogranin A responses and quality of life scores for nearly all subjects

 

KNOXVILLE, TN, -- Provectus (OTCQB: PVCT) today announced that preliminary safety, response, biomarker, and quality of life results from the Company's ongoing Phase 1 clinical trial of single agent PV-10 for the treatment of symptomatic neuroendocrine tumors (NET) metastatic to the liver (mNET) 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, hepatocellular carcinoma, and metastatic liver cancers such as uveal melanoma in single-agent and combination therapy settings.

This single-center Phase 1 study is being conducted at The Queen Elizabeth Hospital in Adelaide, Australia to evaluate the potential safety, tolerability, and preliminary efficacy of PV-10 in mNET patients (NCT02693067). The primary endpoint for the trial is safety, and secondary endpoints include objective response rate (ORR) of injected target and measurable bystander lesions, target lesion somatostatin receptor expression, and biochemical response. Six patients in the first cohort each received one percutaneously-administered injection of PV-10 to one target lesion per treatment cycle. Patients in the second cohort can receive PV-10 injection of multiple lesions per cycle (2 of 6 patients in the second cohort have received at least one cycle of PV-10 thus far).

Preliminary Results from the Presentation at ASCO:

  • Baseline characteristics (N=6): 67% men; median age of 65 years (range 47-72).
  • Disease characteristics: primary tumor site – 50% small intestine, 33% pancreas, and 17% caecal; 87% Grade 2 (well differentiated, intermediate); all patients were refractory to systemic somatostatin analogues and peptide receptor radionuclide therapy.
  • PV-10 treatment summary: Median of 1 cycle (mean 1.7, range 1-4) and median dose per cycle of 2.1 mL (range 1.0-5.8 mL).
  • Preliminary safety: Acceptable toxicity (e.g., post-procedure pain, carcinoid flare, nausea); liver function tests have remained stable.
  • Preliminary target lesion efficacy: 50% objective response and 87% disease control; response follow-up in 3 patients (50%) is ongoing
  • Preliminary patient-level efficacy data were not available at the time of data cutoff.
  • Preliminary clinical and biomarker outcomes: overall quality of life scores were stable in 5 patients (87%); Chromogranin A responses were stable in 5 patients (87%)
  • Preliminary changes in peripheral blood mononuclear cells were not available at the time of data cutoff.

Dominic Rodrigues, Vice Chair of the Company's Board of Directors, said, "Patients with neuroendocrine tumors remain a cancer population with high unmet medical need. This poster describes Provectus' continued progress towards demonstrating the widespread use of small molecule oncolytic immunotherapy PV-10 for the treatment of immunologically ‘cold' or non-T cell inflamed tumor types."

Mr. Rodrigues added, "Patients in this study experienced no safety concerns from single or repeated injections of PV-10 into the liver. Furthermore, we believe PV-10 treatment provided in this trial yielded encouraging, preliminary evidence of single-agent drug activity, including both local and systemic disease control."

A copy of the ASCO poster presentation is currently available on Provectus' website at https://www.provectusbio.com/media/docs/publications/PV-10-NET-01_ASCO2019.pdf.

About Neuroendocrine Tumors

NET associated with the gastrointestinal tract are frequently indolent but troublesome as a result of endocrine secretory properties and a propensity for metastasis to the liver, nodes, and lungs. mNET located in the midgut and liver often secrete vasoactive products, giving rise to "Carcinoid Syndrome" (e.g., flushing, diarrhea, wheezing, abdominal cramps, and peripheral edema).

About PV-10

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.

About Provectus

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.

References

  1. Wachter et al. Functional Imaging of Photosensitizers using Multiphoton Microscopy. Proceedings of SPIE 4620, 143, 2002.
  2. Liu et al. Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1. Oncotarget 7, 37893, 2016.
  3. Qin et al. Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death. Cell Death and Disease 8, e2584, 2017.
  4. Liu et al. T cell mediated immunity after combination therapy with intralesional PV-10 and blockade of the PD-1/PD-L1 pathway in a murine melanoma model. PLoS One 13, e0196033, 2018.
  5. Swift et al. Potent in vitro and xenograft antitumor activity of a novel agent, PV-10, against relapsed and refractory neuroblastoma. Onco Targets Ther 12:1293-1307, 2019.

This study was the subject of a trials in progress poster presented at the ESMO 2018 Congress (the European Society for Medical Oncology annual meeting), held in Munich, Germany from October 19-23.

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).

Contact:

Provectus Biopharmaceuticals, Inc.
Heather Raines, CPA
Chief Financial Officer
Phone: 866-594-5999

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