Provectus Biopharmaceuticals Announces New Data from Combination Therapy Trial of Small Molecule Cancer Immunotherapy PV-10® and Keytruda® for First-Line Stage III Melanoma at Melanoma Bridge 2022

Rhea-AI Summary

Provectus presented promising results from its ongoing Phase 1b/2 study of PV-10 and Keytruda for treating Stage III cutaneous melanoma at Melanoma Bridge 2022. Highlights include a 50% complete response rate (3/6 patients) and an 83% overall response rate (5/6 patients). Rapid complete responses were observed within 15 to 27 weeks. The study reported an 83% progression-free survival rate and a 100% overall survival rate for complete responders after 18 to 36 months. The findings suggest significant potential for the combination therapy, with plans for a Phase 2/3 trial in 2023.

Positive

• 50% complete response rate and 83% overall response rate in Phase 1b/2 study.
• Rapid complete responses achieved within 15 to 27 weeks.
• 83% progression-free survival rate during the 2-year treatment interval.
• 100% overall survival rate for complete responders after 18 to 36 months.

Negative

• None.

• 50% CR and 83% ORR by RECIST 1.1 criteria
• Rapid CRs achieved within 15 to 27 weeks
• Median PFS not reached during 2-year treatment interval; 83% PFS rate
• 100% OS rate for CRs; ongoing after 18 to 36 months of study follow-up

KNOXVILLE, TN, Dec. 01, 2022 (GLOBE NEWSWIRE) -- Provectus (OTCQB: PVCT) today announced that new data from the Company’s ongoing, multi-cohort, Phase 1b/2 study of the combination of small molecule cancer immunotherapy PV-10, an intratumoral formulation of Provectus’ rose bengal sodium (RBS) active pharmaceutical ingredient, and anti-PD-1 therapy Keytruda (pembrolizumab) for the treatment of immune checkpoint blockade (CB)-naïve Stage III cutaneous melanoma (NCT01223415) are being presented at Melanoma Bridge 2022 in Naples, Italy and online from December 1-3, 2022.

Entitled “Response for combination of PV-10 autolytic immunotherapy and immune checkpoint blockade in stage III cutaneous melanoma,” the video oral communication and poster presentation are available by clicking on the Company website links below:

• The video communication narrated by Chief Technology Officer Eric Wachter, PhD, and
• The conference poster.

Key Highlights of the Melanoma Bridge 2022 Presentation:

• Efficacy (6 patients; investigator-assessed RECIST v1.1) 
  • 50% complete response (CR) (3/6) and 83% overall response rate (ORR) (5/6)
  • Rapid CRs – 2 within 15 weeks and 1 within 27 weeks
    
• Durability
  
  
  • Median progression-free survival (PFS) not reached during 2-year treatment interval; 83% PFS rate
  • All CRs ongoing after 18 to 36 months of study follow-up
    
• Survival
  
  
  • Median overall survival (OS) not reached
  • 100% OS rate for CRs; ongoing after 18 to 36 months of study follow-up
    
• Safety
  
  
  • Consistent with established patterns of PV-10 and Keytruda single-agent use
  • Consistent with prior PV-10 and Keytruda combination therapy cohorts of CB-naïve and CB-refractory advanced melanoma patients^1,2
    
• Mechanism of immune action
  
  
  • Precise, increased, PV-10-induced T-cell activity preceded CR
  • Similar immune upregulation observed in (a) monotherapy PV-10 treatment of Stage III melanoma patients³ and (b) PV-10 and Keytruda combination treatment of CB-refractory advanced melanoma patients²
    

Dominic Rodrigues, Vice Chair of Provectus’ Board of Directors said, “These data demonstrate the potential for rapid, durable, complete response in Stage III melanoma patients by combining individually active anticancer agents PV-10 and checkpoint blockade. Intratumoral PV-10 treatment and as-needed retreatment of baseline and any new melanoma lesions use checkpoint blockade to boost the precise, tumor-specific, systemic adaptive immune response generated from the response of PV-10-injected lesions to drive robust patient outcomes.”

Planned Combination PV-10 and CB Treatment of 1^st-Line Stage III Melanoma

Successfully combining PV-10 and CB in Stage III melanoma patients (50% CR and 83% ORR) is predicated on achieving rapid response of PV-10-injected lesions that may lead to rapid, durable CR of patients and ultimately to improved PFS and OS:

• Single-agent PV-10 achieved 56% CR (and 63% ORR) of injected lesions in Stage III patients⁴, but only 23% CR (and 54% ORR) of non-injected lesions, and a median PFS of 8.9 to 9.8 months ⁵,
  
• Single-agent CB may exhibit a similar response rate in Stage III (M0) patients (27% CR and 54% ORR) to PV-10’s response rate in non-injected lesions, with a median PFS of 11.7 months ⁶, and
  
• The combination of PV-10 and CB in CB-naïve Stage IV patients has shown the potential for significant combinational interaction and durability, while also presenting a non-overlapping safety profile^1,7.
  

Mr. Rodrigues added, “To prove the synergistic clinical benefit of combining PV-10 and checkpoint blockade for the first-line treatment of Stage III melanoma, we plan to initiate a Phase 2/3 randomized control trial of PV-10 and standard of care checkpoint blockade versus standard of care checkpoint blockade in 2023. This trial is essentially a head-to-head comparison of PV-10 combination therapy and monotherapy Keytruda.”

About Provectus

Provectus Biopharmaceuticals, Inc. (Provectus or the Company) is a clinical-stage biotechnology company developing immunotherapy medicines for different diseases that are based on a class of synthetic small molecule immuno-modulators called halogenated xanthenes (HXs). Provectus’ lead HX molecule is named rose bengal sodium (RBS).

The Company’s proprietary, patented, pharmaceutical-grade RBS is the active pharmaceutical ingredient (API) in the drug product candidates of Provectus’ clinical development programs and the preclinical formulations of the Company’s drug discovery programs. Importantly, Provectus’ pharmaceutical-grade RBS displays different therapeutic effects at different concentrations and can be formulated for delivery by different routes of administration. The International Nonproprietary Names (INN) Expert Committee of the World Health Organization (WHO) selected “rose bengal sodium” for the nonproprietary name of the Company’s API.

RBS may target disease in a bifunctional manner. First, direct contact may lead to cell death or repair depending on the disease being treated and the concentration of Provectus’ RBS utilized in the treatment. Secondly, multivariate immune signaling, activation, and response may follow that may manifest as stimulatory, inhibitory, or both.

The Company believes that it is the first entity to advance an RBS formulation into clinical trials for the treatment of a disease, such as those trials reported on the clinical trials registry ClinicalTrials.gov. Provectus also believes that it is the first and only entity to date to successfully, reproducibly, and consistently make pharmaceutical-grade RBS at a purity of nearly 100%.

Provectus’ small molecule HX medical science platform includes clinical development programs in oncology, dermatology, and ophthalmology; proof-of-concept in vivo drug discovery programs in oncology, hematology, wound healing, and animal health; and preclinical in vitro drug discovery programs in infectious diseases and tissue regeneration and repair.

Information about the Company’s clinical trials can be found at the National Institutes of Health (NIH) registry, www.clinicaltrials.gov. For additional information about Provectus, please visit the Company’s website at www.provectusbio.com.

Trademarks

PV-10^® is a registered trademark of Provectus, Knoxville, Tennessee, U.S.A.

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

References

1. A phase 1b study of rose bengal disodium and anti-PD-1 in metastatic cutaneous melanoma: results in patients naïve to immune checkpoint blockade, Agarwala et al. European Society for Medical Oncology (ESMO) Virtual Congress 2020. The Company is developing and planning to publish a manuscript with principal investigators in 2023 of 5-year landmark survival.
2. Response for combination of PV-10 autolytic immunotherapy and immune checkpoint blockade in checkpoint-refractory patients, Zager et al. Melanoma Bridge 2020. Provectus plans to present updated data of this patient cohort at a medical conference in 2023.
3. Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1, Liu et al. Oncotarget. 2016; 7:37893-37905.
4. Lesion-Level Response to Single-Agent PV-10 in Stage III Cutaneous Melanoma, Wachter et al. Society for Melanoma Research (SMR) Virtual Congress 2021.
5. Phase 2 Study of Intralesional PV-10 in Refractory Metastatic Melanoma, Thompson et al. Ann Surg Oncol (2015) 22:2135–2142.
6. Efficacy of immune checkpoint inhibitors for in-transit melanoma, Nan Tie et al. J Immunother Cancer 2020;8:e000440.
7. Developing combination strategies using PD-1 checkpoint inhibitors to treat cancer, Schmidt. Semin Immunopathol. 2019 Jan;41(1):21-30.
   

FORWARD-LOOKING STATEMENTS: The information in this press release may include “forward-looking statements,” within the meaning of U.S. securities legislation, relating to the business of Provectus and its affiliates, which are based on the opinions and estimates of Company management and are subject to a variety of risks and uncertainties and other factors that could cause actual events or results to differ materially from those projected in the forward-looking statements. Forward-looking statements are often, but not always, identified by the use of words such as “seek,” “anticipate,” “budget,” “plan,” “continue,” “estimate,” “expect,” “forecast,” “may,” “will,” “project,” “predict,” “potential,” “targeting,” “intend,” “could,” “might,” “should,” “believe,” and similar words suggesting future outcomes or statements regarding an outlook.

The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated or that such agents as products will achieve any particular revenue levels.

Due to the risks, uncertainties, and assumptions inherent in forward-looking statements, readers should not place undue reliance on these forward-looking statements. The forward-looking statements contained in this press release are made as of the date hereof or as of the date specifically specified herein, and Provectus undertakes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except in accordance with applicable securities laws. The forward-looking statements are expressly qualified by this cautionary statement.

Risks, uncertainties, and assumptions include those discussed in the Company’s filings with the Securities and Exchange Commission (SEC), including those described in Item 1A of:

• The Company’s Annual Report on Form 10-K for the period ended December 31, 2021, and
  
  
• Provectus’ Quarterly Report on Form 10-Q for the period ended September 30, 2022.
  
  

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Contact:

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

FAQ

What were the results of Provectus' Phase 1b/2 study on PV-10 and Keytruda?

Provectus reported a 50% complete response rate and an 83% overall response rate in their Phase 1b/2 study for Stage III melanoma.

What is the significance of the survival rates reported in the Phase 1b/2 study?

The study reported an 83% progression-free survival rate and a 100% overall survival rate for patients with a complete response after 18 to 36 months.

When does Provectus plan to initiate the Phase 2/3 trial?

Provectus plans to start the Phase 2/3 randomized control trial in 2023.

Where were the study results presented?

The results were presented at the Melanoma Bridge 2022 conference in Naples, Italy.

What is the combination therapy being studied by Provectus?

The therapy involves the combination of PV-10, an intratumoral formulation of rose bengal sodium, and the anti-PD-1 therapy Keytruda.