ARTICLE COMPARING SURVIVAL OUTCOMES OF ISOLATED LIMB INFUSION VERSUS PV-10 FOR IN-TRANSIT MELANOMA PUBLISHED IN JOURNAL OF SURGICAL ONCOLOGY

- 72 patients were treated with either ILI or PV-10 at Australia’s Princess Alexandra Hospital; data were prospectively recorded; primary outcome was melanoma-specific survival; ILI is historical standard of care at reporting institution

- Regionally-administered ILI and intratumorally-delivered PV-10 provided comparable long-term survival for in-transit melanoma patients

KNOXVILLE, TN, Jan. 29, 2019 (GLOBE NEWSWIRE) -- Provectus (OTCQB: PVCT) today announced that the Journal of Surgical Oncology (JSO) has published results from an investigator-conceived and led, single-center study of in-transit melanoma (ITM) patients receiving either regionally-administered isolated limb infusion (ILI) or intratumoral (aka intralesional) PV-10 to assess and compare the effect of these treatments on survival. The JSO article detailed the work of investigators at , where ILI represents the historical standard of care for ITM and PV-10 was used to treat ITM under expanded access. Intratumoral injection of PV-10 can yield immunogenic cell death in solid tumor cancers and stimulate tumor-specific reactivity in circulating T cells.^1,2,3,4

This article, entitled “,” may be accessed via the JSO's website at .⁵

Key Results from the JSO Article:

• Baseline and disease characteristics:
  
   
  • Patients matched for key covariates: age, gender, primary disease site, and Breslow thickness
  • ILI: 36 patients; 56% men; median age of 76.5 years (interquartile range 69-83); 100% Stage IIIB/IIIC
  • PV-10: 36 patients; 56% men; median age of 74.5 years (65-81); 89% Stage IIIB/IIIC (11% Stage IV)
    
     
• Treatment response (patient-level best overall response):
  
   
  • ILI: 22% complete response and 50% overall response rate
  • PV-10: 25% complete response and 83% overall response rate
    
     
• Survival outcomes:
  
   
  • ILI
    • progression-free survival (PFS): median of 5.0 months (interquartile range 2.7-10.7)
    • disease-free survival (DFS): median of 16.5 months (8.9-48.4)
    • overall survival (OS): median of 29.7 months (12.3-88.5)
    • melanoma-specific survival (MSS): median of 74.4 months (24.3-NA); 12‐, 24‐, 36‐, and 60‐month MSS rates of 85%, 75%, 60%, and 60%, respectively
  • PV-10
    • PFS: median of 3.9 months (9.6-47.9)
    • DFS: median of 14.1 months (4.5-20.9)
    • OS: median of 27.1 months (14.3-48.6)
    • MSS: median of 36.4 months (16.6-65.3); 12‐, 24‐, 36‐, and 60‐month MSS rates of 83%, 70%, 54%, and 36%, respectively
  • Differences in PFS, DFS, and MSS comparing ILI with PV‐10 were not statistically significant

Among the authors’ conclusions:

• “Overall these results demonstrate that demographically similar patients with in-transit melanoma metastases treated with ILI or PV-10 have comparable long-term survival rates,”
  
   
• “Propensity score matching is a useful statistical technique for examining relative treatment effects within complex patient groups, particularly when larger randomized controlled studies are impractical,”
  
   
• “A complete response to either treatment was the only independent factor identified that significantly predicted long-term survival,”
  
   
• “These findings suggest that both ILI and PV‐10 can be considered as a suitable standard of care,” and
  
   
• “These treatments are relevant and likely to remain of value in the near future, particularly for the treatment of symptomatic or refractory metastases following the discontinuation of systemic therapies due to serious drug-related side-effects or exhaustion of other systemic options.”

Dominic Rodrigues, Vice Chair of the Company’s Board of Directors, said, “Despite the advances made by targeted therapies and checkpoint inhibitors, these comparative survival data highlight the important role that investigational PV-10 may have for the treatment of advanced melanoma. The Australian investigators place PV-10’s role in the context of relatively more expensive systemic agents that have substantial toxicity profiles and similar response rates.”

Mr. Rodrigues added, “Furthermore, these comparative survival data substantiate the Company’s historical work in melanoma and provide more validation of PV-10 in a single-agent setting for a challenging patient population. The key focus of Provectus’ drug development program now is to demonstrate PV-10 activity in both single-agent and combination therapy settings for the treatment of both hot and cold tumor types.”

About PV-10

Provectus’ lead investigational oncology drug, PV-10, the first small molecule oncolytic immunotherapy, . PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver, and .

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, . For additional information about Provectus, please visit the Company's website at .

References

1. Wachter et al. . Proceedings of SPIE 4620, 143, 2002.

2. Liu et al. . Oncotarget 7, 37893, 2016.

3. Qin et al. . Cell Death and Disease 8, e2584, 2017.

4. Liu et al. . PLoS One 13, e0196033, 2018.

5. The JSO previously published results from a PAH investigator-led, single-center study of patients with ITM who received intralesional PV-10 under expanded access. This JSO article, entitled “,” detailed the experience of PAH investigators treating 45 patients with almost exclusively Stage III disease from 2008 to 2015. The article may be accessed via the JSO's website at .

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