Provectus Announces Presentation of Updated Results from Phase 1B Trial of PV-10 in Combination with KEYTRUDA® (Pembrolizumab) for Treatment of Advanced Melanoma at SMR 2018 Congress

Thursday October 25, 2018
  • -   Single-agent adverse effect profiles of PV-10 and Keytruda were maintained
  • -   65% overall objective response rate with 9% complete response, via RECIST 1.1

KNOXVILLE, TN, /GLOBE NEWSWIRE/ -- Provectus (OTCQB: PVCT) today announced that interim results from the Company's ongoing Phase 1b/2 study of small molecule oncolytic immunotherapy PV-10 in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 immune checkpoint inhibitor, were presented at the 15th International Congress of the Society for Melanoma Research (SMR 2018 Congress), held in Manchester, England from October 24-27, 2018. Intratumoral injection of PV-10 can yield immunogenic cell death in solid tumor cancers and stimulate tumor-specific reactivity in circulating T cells.1-4

The Phase 1b portion of the study completed enrollment in April 2018 of 23 patients with metastatic melanoma at clinical sites in the U.S. (NCT02557321). Patients with at least one injectable lesion and who were candidates for KEYTRUDA were eligible. 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 and progression-free survival 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%) is ongoing.

Interim Results from the Presentation at SMR:

  • Baseline characteristics: 83% men; median age of 70 years (range 28-90) and 70% > 65 years; 91% checkpoint naïve.
  • Disease characteristics: 13% Stage IIIC/IIID and 52% Stage IV M1b/M1c; median of 2 cutaneous/subcutaneous lesions (range 1-15)5; most subjects had substantial non-injected systemic disease burden in addition to their injectable cutaneous and/or subcutaneous lesions.
  • Treatment summary: Subjects received a median of 4 cycles of PV-10 (mean 3.7, range 1-5) and a median of 5 injections of PV-10 (range 1-82); PV-10 was not administered after week 12.
  • Preliminary safety: adverse events were consistent with the established patterns for single-agent use of each drug; there were no unexpected toxicities or evidence of significant overlapping toxicity.
  • Preliminary target lesion efficacy (best overall response): 43% complete response and 65% objective response.
  • Preliminary overall efficacy (per RECIST 1.1): 9% complete response, 65% objective response, and 70% clinical benefit; 83% objective response in M1c patients.

The Company currently plans to present durability and survival data from these study participants at a medical conference in the first half of 2019. Provectus plans to open an expansion cohort of up to 24 patients in the Phase 1b portion of the study to assess the PV-10-KEYTRUDA combination in patients who have failed to respond to initial treatment with checkpoint inhibition.

Dominic Rodrigues, Vice Chair of the Company's Board of Directors, said, "These updated results continue to highlight the non-overlapping safety profiles of PV-10 and checkpoint inhibition by authenticating the lack of correlation of adverse events between the two drugs. The data also continue to demonstrate the promising clinical benefit of cancer combination therapy with checkpoint inhibition after minimal PV-10 intervention.6 We believe successful combination therapy is achieved by pairing drugs that each show single-agent activity."

A copy of the poster presentation is currently available on Provectus' website at https://www.provectusbio.com/media/docs/publications/SMR2018_Poster_PV-10_Pembro.pdf.

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 Biopharmaceuticals, Inc. (Provectus or the Company) is a clinical-stage biotechnology company leading the development of a new class of drugs based on halogenated xanthenes, which are chemical small molecules. 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. Carvajal et al. Metastatic disease from uveal melanoma: treatment options and future prospects. The British Journal of Ophthalmology. 2017;101(1):38-44.
  6. Two patients with baseline burden too numerous to count (TNC) were excluded from this calculation.
  7. To date, clinical trial and expanded access patients have received the combination of PV-10 and checkpoint inhibition for advanced melanoma (+KEYTRUDA), mucosal melanoma of the vagina (+KEYTRUDA), Merkel cell carcinoma (+BAVENCIO®), breast cancer (+OPDIVO®), and uveal melanoma metastatic to the liver (+OPDIVO and YERVOY®).

Trademark

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.

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).

Contact:

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

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