- 29% of M1a patients achieved metabolic complete response (mCR)
- mCR patients alive up to >4 years after start of PV-10 treatment
- PET tumor response assessment more accurate than 2D EASL or RECIST
- PV-10 combination therapy with checkpoint blockade may offer durable responses to early-stage metastatic uveal melanoma patients
KNOXVILLE, TN, June 08, 2022 (GLOBE NEWSWIRE) -- Provectus (OTCQB: PVCT) today announced that updated data from the Company’s initial expansion cohort of patients with uveal melanoma metastatic to the liver (mUM) in its cancers-of-the-liver Phase 1 trial of investigational immunocatalyst PV-10 (rose bengal sodium) (NCT00986661) were presented at the 2022 American Society of Clinical Oncology (ASCO) annual meeting, held June 3-7 in Chicago, Illinois and online.
Twenty-nine percent (29%) of Stage IV M1a mUM patients achieved mCR and were alive from 12.4+ to 48.8+ months after starting PV-10 treatment. All M1a patients had hepatic metastases injected with PV-10; 50% had extrahepatic disease, which was not injected with PV-10. A portion of M1a patients underwent positron emission tomography (PET)-computed tomography (CT) (PET-CT) cancer imaging, which previously has not been widely recognized as an important tool for monitoring tumor response in mUM because historical treatments essentially did not produce mCRs.
This ongoing single-center mUM study at MD Anderson Cancer Center (MDACC) in Houston, Texas has been led since inception by Sapna Patel, MD, Associate Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine at MDACC. Up to three hepatic mUM tumors can be injected per PV-10 treatment cycle. Response assessments are performed at Day 28, and then every three months. Patients with additional, injectable, visceral hepatic mUM disease may receive additional cycles of PV-10 after Day 28. Eligible patients may also receive standard of care immune checkpoint blockade (CB; i.e., either PD-1 or combination CTLA-4 + PD-1) during and after PV-10 treatment.
Highlights from the ASCO presentation, with data supplementation
Baseline characteristics
| All patients | mCR responders | |||
| # of patients | 23 | 4 | ||
| Men | 52 | % | 50 | % |
| Median age (range) | 64 (32-80) | 68 (56-70) | ||
| Disease stage | ||||
| M1a | 61 | % | 100 | % |
| M1b | 35 | % | - | |
| M1c | 4 | % | - | |
| Disease location | ||||
| Hepatic only | 52 | % | 50 | % |
| Hepatic + extrahepatic | 48 | % | 50 | % |
| Prior CB treatment | ||||
| CB-naïve | 49 | % | 50 | % |
| CB-refractory | 51 | % | 50 | % |
| PV-10 treatment summary | ||||
| PV-10 monotherapy | 26 | % | 25 | % |
| PV-10 + PD-1 | 26 | % | - | |
| PV-10 + CTLA-4 + PD-1 | 49 | % | 75 | % |
| # of PV-10 treatment cycles | median 2 (range 1-6) | 1.5 (1-3) | ||
| # of PV-10-injected lesions | 2 (1-11) | 2 (1-3) | ||
PV-10-injected Lesion Efficacy
| All patients | mCR responders | |||
| RECIST | ||||
| # of injected lesions | 59 | 8 | ||
| Complete response (CR) | 0 | % | 0 | % |
| Partial response (PR) | 19 | % | 50 | % |
| Overall response rate (ORR) | 19 | % | 50 | % |
| Stable disease (SD) | 66 | % | 50 | % |
| Disease control rate (DCR) | 85 | % | 100 | % |
| 2D EASL | ||||
| # of injected lesions | 58 | 8 | ||
| Complete response (CR) | 7 | % | 0 | % |
| Partial response (PR) | 28 | % | 50 | % |
| Overall response rate (ORR) | 34 | % | 50 | % |
| Stable disease (SD) | 52 | % | 38 | % |
| Disease control rate (DCR) | 85 | % | 88 | % |
Safety: Acceptable safety was observed with no mortality or permanent Grade 3 or higher morbidity attributed to study treatment
Overall survival from the start of PV-10 treatment (months)
| All patients | mCR responders | |
| Median | 10.7 | Not reached |
| Range | 1.1 to 48.8+ | 12.4+ to 48.8+ |
Conclusions
- PV-10 can induce mCR in injected/adscopal and non-injected/abscopal lesions.
- mCR suggests immunogenic cell death in mUM patients with non-injected liver metastases.
- RECIST response assessment may underestimate the effect of PV-10 in injected tumors. 2D EASL is more sensitive than RECIST to changes in injected lesions. PET-CT is more sensitive than either RECIST or 2D EASL.
- Translational research is underway at MDACC and Moffitt Cancer Center to elucidate the molecular basis for mCR responders vs non-responders.
A copy of the ASCO poster presentation is available on Provectus’ website at: https://www.provectusbio.com/media/docs/publications/ASCO_2022_PV-10-LC-01.pdf.
Ed Pershing, Chair of Provectus’ Board of Directors (Board), said, “We could not be more grateful to these study patients, their families and caregivers, the MD Anderson Cancer Center clinical trial team, and the ocular melanoma patient advocacy community for the opportunity to better develop a comprehensive approach for identifying, surveilling, treating, and hopefully defeating this terrible disease in its early metastatic stage. We have gained valuable insights from this clinical trial that will be considered for future patient assessment and treatment protocols, as we continue to advance PV-10 for the treatment of metastatic uveal melanoma.”
Dominic Rodrigues, Vice Chair of the Board, added, “These clinical trial data show that, while PV-10 can contribute to treatment efficacy across all disease stages, PV-10 may have much greater impact on early-stage metastatic uveal melanoma. It is important to note that patients do not typically present with M1a, M1b, or M1c disease, and that staging of study participants is based on the status of their metastatic disease course at the start of PV-10 treatment. The outcome in M1a patients who achieved a metabolic complete response implies that early intervention can be critical, and that surveillance techniques like PET imaging can play an essential role in identifying metastatic status and assessing treatment response.”
Mr. Rodrigues concluded, “Metastatic uveal melanoma can be particularly threatening once it takes hold at metastatic sites around the body. These study data give us a level of confidence that the potential exists to provide a survival benefit to patients with metastatic disease by leveraging standard of care immunotherapy in combination with PV-10, and to finalize the development of a PV-10-led approach that could offer durable responses in patients by proactively integrating assessment and treatment methodologies earlier and not waiting for a patient’s disease to get out of control.”
About Provectus
Provectus Biopharmaceuticals, Inc. (Provectus or the Company) is a clinical-stage biotechnology company developing immunotherapy medicines for different disease areas based on a class of small molecules called halogenated xanthenes (HXs). The Company’s lead molecule is RBS. A second HX molecule has been synthesized.
Provectus’ drug discovery and development programs include investigational drugs and drug targets in oncology (clinical-stage), dermatology (clinical-stage), hematology, virology, microbiology, ophthalmology (clinical-stage), and animal health, and use multiple routes of administration, such as intralesional (IL), topical (.top), oral (P.O.), inhaled (.inh), intranasal (IN), and intravenous (IV).
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.
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 March 31, 2022.
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Contact:
Provectus Biopharmaceuticals, Inc.
Heather Raines, CPA
Chief Financial Officer
Phone: (866) 594-5999
