Provectus Biopharmaceuticals Provides Update on Melanoma Clinical Development Program for Investigational Drug PV-10

Thursday December 6, 2018
  • Lesion-level response data from main cohort of advanced melanoma patients naïve to immune checkpoint inhibition in Phase 1b/2 combination study of PV-10 and KEYTRUDA® (pembrolizumab) presented at Melanoma Bridge 2018; 77% complete response of injected target lesions achieved across all disease stages
  • Phase 1b/2 combination study to add expansion cohort of patients with satellite or in-transit melanoma (Stage IIIB/C/D); patients typically naïve to checkpoint inhibition

KNOXVILLE, TN, /GLOBE NEWSWIRE/ -- today provided several updates on the Company's melanoma drug development program for its lead investigational agent and small molecule oncolytic immunotherapy PV-10. 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

Update #1. The Company announced that lesion-level response data from the main cohort of patients in the Phase 1b portion of its Phase 1b/2 clinical trial of PV-10 in combination with KEYTRUDA® (pembrolizumab) for the treatment of advanced melanoma (NCT02557321) were presented at Melanoma Bridge 2018, held in Naples, Italy from November 30-December 1, 2018. The main cohort was comprised of 20 Stage IV and 3 Stage III melanoma patients, the majority of whom were naïve to checkpoint inhibition.

Summary Results from the Presentation at Melanoma Bridge:

  • Complete response (CR) of injected target lesions for the combination of PV-10 and pembrolizumab was higher than historical CR for single-agent PV-10 (NCT00521053) across all disease stages: 77% vs 46%;
  • CR of injected target lesions for the combination was higher than CR for single-agent PV-10 for each of these stages:
    • 73% vs 0% for Stage IV M1a,
    • 71% vs 4% for Stage IV M1b, and
    • 100% vs 17% for Stage IV M1c;
  • Although data on combination treatment of Stage III disease is currently limited, CR of injected target lesions for the combination was higher than CR for single-agent PV-10: 67% vs 54%; and
  • 40% of injected target lesions achieved CR after one or two injections.

A copy of the Melanoma Bridge 2018 poster presentation is currently available on Provectus' website at https://www.provectusbio.com/media/docs/publications/Melanoma_Bridge_2018-Poster-PV-10-29-Nov-2018.pdf.

In October 2018, interim safety and patient-level response data of the main cohort were reported at the 15th International Congress of the Society for Melanoma Research. Overall efficacy (RECIST 1.1) was 9% CR, 65% objective response, and 70% clinical benefit, including 83% objective response in Stage IV M1c patients.

Update #2. The Company will further expand the Phase 1b portion of the PV-10-pembrolizumab combination study to include a cohort of up to 24 patients who have satellite or in-transit disease (Stage IIIB/C/D melanoma). A first expansion cohort currently is enrolling up to 24 patients with advanced melanoma (Stage IV) who are refractory to checkpoint inhibition.

Update #3. As a result of this latest expansion of the Phase 1b combination study to treat a patient population who overlap with those of Provectus' Phase 3 trial of single-agent PV-10 for locally advanced cutaneous melanoma (NCT02288897, Stage IIIB-IV M1a), the Company is placing a hold on Phase 3 trial enrollment to allow for a more thorough performance analysis and comparison of PV-10 combination therapy versus historical single-agent PV-10 treatment for these patients. The Company also will invite Phase 3 trial investigators to participate in this new Phase 1b combination study cohort.

Mr. Dominic Rodrigues, Vice Chair of the Company's Board of Directors, said, "Systemic therapy with immune checkpoint inhibition is now recommended in the US for Stage III melanoma patients with satellite or in-transit disease. Given the changes in the melanoma treatment landscape over the last several years, as well as recent trends shaping drug development in melanoma, it is prudent for Provectus to assess PV-10's positioning for this population of Stage III patients."

Mr. Rodrigues added, "While enrollment in our Phase 3 trial has been challenging because of the tight eligibility criteria emanating from this study's original design, we look forward to strong investigator interest to enroll patients in the new expansion cohort of our Phase 1b combination study of PV-10 and pembrolizumab, which has less restrictive eligibility."

Mr. Rodrigues concluded, "The KEYNOTE-001 study of single-agent pembrolizumab demonstrated lower overall response in Stage III versus Stage IV patients and also in subcutaneous versus visceral lesions.5-6

The combination of PV-10 and pembrolizumab may represent a better treatment solution for Stage III patients than either agent alone, through the rapid and complete reduction in tumor burden from PV-10 injection, followed by the potential synergy of the two agents' respective mechanisms of action."

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. Ribas et al. Efficacy and safety of the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in 411 patients (pts) with melanoma (MEL). ASCO Annual Meeting 2014. J Clin Oncol 32:5s (suppl; abstr LBA9000^), 2014.
  6. Lee et al. Metastasis-specific patterns of response and progression with anti-PD-1 treatment in metastatic melanoma. Pigment Cell Melanoma Res 31, 404, 2018.

Trademark

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