Melanoma Clinical Trial Update

A summary of all open and completed clinical trials is available at our Clinical Trial Information page.

  • In December 2015 Dr. Sanjiv Agarwala (Professor of Medicine, Temple University; Chief of Oncology and Hematology, St. Luke's Cancer Center in Bethlehem, PA) presented at the Melanoma Bridge 2015 meeting in Naples, Italy. In the presentation, entitled "Overview of Intralesional Therapy for Melanoma", Dr. Agarwala discusses the importance and potential goals of intralesional therapy in the treatment of melanoma.
  • In November 2015 data from the phase 1 PV-10 mechanism of action study were presented at the Society for Immunotherapy of Cancer 30th Annual Meeting by Moffitt Cancer Center researchers in a poster presentation entitled "Intralesional Rose Bengal in Melanoma Elicits Tumor Immunity via High Mobility Group Box 1". In the reported work, the authors showed that tumor-specific T cells were increased in the blood after tumor ablation with PV-10. This was initiated by tumor cell necrosis, leading to release of High Mobility Box Group 1 (HMBG1), one of a class Damage-Associated Molecular Pattern molecules (DAMPs) released by dying cancer cells that can lead to activation of dendritic cells. HMBG1 release was observed in vitro and after ablation of melanoma tumors. This was also correlated with dendritic cell activation and infiltration into lymph nodes draining ablated tumors.
  • In June 2015 Dr. Vernon Sondak (Moffitt Cancer Center, Tampa, FL, USA) presented data on "Intralesional Therapy for Melanoma with PV-10" during the 5th European Post-Chicago Melanoma/Skin Cancer Meeting in Munich, Germany.

    In addition, the poster titled "Trials in Progress: Intralesional Rose Bengal vs Systemic Chemotherapy for Treatment of Locally Advanced Cutaneous Melanoma," which details the phase 3 clinical trial that began recently, was also presented at the meeting.

  • In May 2015 Dr. Sanjiv Agarwala, chief of medical oncology and hematology at St. Luke's Cancer Center in Bethlehem, Pennsylvania, and professor of medicine at Temple University School of Medicine in Philadelphia, presented data on PV-10 as an investigational intralesional treatment of melanoma at the 2015 American Society of Clinical Oncology's Annual Meeting in a presentation entitled "A Changing Topography: The Role of Intralesional Therapy in Melanoma".

  • In April 2015 patient enrollment began for a phase 3 clinical trial of PV-10. The study is an international multicenter, open-label, randomized controlled trial (RCT) of single-agent intralesional PV-10 versus systemic chemotherapy with dacarbazine (DTIC) or temozolomide (TMZ) to assess treatment of locally advanced cutaneous melanoma in patients who are BRAF V600 wild-type and have failed or are not otherwise candidates for ipilimumab or another immune checkpoint inhibitor.

  • In March 2015 an amended phase 3 protocol was been submitted to the U.S. FDA. There were a number of minor changes made to the protocol that were addressed during the February Type C meeting. The Company does not require additional FDA review to start the phase 3 study, and has begun the process of gaining IRB approval for the amended protocol. Details regarding the amended protocol are available at ClinicalTrials.gov.

  • In March 2015 the Melanoma Research Foundation hosted a focus group to get a better understanding of the unique concerns and needs of Stage III melanoma patients. The Stage III Focus Group Summary is available online.

  • In February 2015 a Type C meeting was held with the US FDA to review certain operational aspects of the protocol for the planned phase 3 clinical trial of PV-10 for melanoma. Details regarding the endpoints of the study and current inclusion and exclusion criteria are available at ClinicalTrials.gov.

  • In November 2014 a phase 3 protocol for evaluation of PV-10 for treatment of locally advanced cutaneous melanoma was submitted to the FDA.

  • In November 2014 Dr Shari Pilon-Thomas of the Moffitt Cancer Center presented data on intralesional PV-10 in combination with co-inhibitory blockade agents in a poster presentation titled "Efficacy of Intralesional Injection with PV-10 in Combination with Co-Inhibitory Blockade in a Murine Model of Melanoma" at the Society for Immunotherapy of Cancer [SITC] 29th Annual Meeting. The testing assessed response of injected and uninjected B16 melanoma tumors in mice receiving PV-10 alone or in combination with one of three agents designed for co-inhibitory blockade. The tested agents targeted either CLTA-4, PD-1 or PD-L1, the three most common clinical targets for co-inhibitory blockade. In each case, combination of PV-10 with co-inhibitory blockade led to improved tumor response and enhanced anti-tumor immunity of T-cells. Further testing with the anti-PD-L1 agent showed that these improvements could apply to both injected and uninjected tumors.

  • In October 2014 Phase 2 data were published in the Annals of Surgical Oncology in a peer-reviewed article entitled Phase 2 Study of Intralesional PV-10 in Refractory Metastatic Melanoma".

  • In October 2014 Dr. Sanjiv Agarwala of St. Luke's Cancer Center presented data on investigational new drug PV-10 for the treatment of melanoma at the III Eurasian Melanoma and Skin Cancers Forum, in Suzdal, Russia in a presentation entitled "Overview of Intralesional Therapy for Melanoma: Focus on PV-10".

  • In September 2014 subgroup analyses of completed Phase 2 data were presented at the European Society For Medical Oncology 2014 Congress in a poster presentation entitled "Subgroup Efficacy in Patients Receiving Intralesional Rose Bengal to All Existing Melanoma in Phase II Study PV-10-MM-02". The presentation showed that PV-10 elicits a high rate of response in injected tumors through its ablative effect, and additionally, that the durability of response as well as the bystander response in uninjected tumors implicate an additional immunologic mechanism secondary to ablation. Tumors were no longer detectable (complete response or CR) in 26% of the study population. This response was particularly evident in patients who had all existing lesions injected with PV-10 (i.e., All Lesions Treated subgroup, 50% CR; Confidence Interval: 31-69%). These 28 patients had as many as 20 lesions confined to the skin, and experienced a mean PFS of 9.8 months. For an additional 26 patients who had all their disease treated with the exception of 1-2 designated, untreated bystander lesions, mean PFS was 8.9 months.

  • In June 2014 a poster presentation entitled "Efficacy of intralesional rose bengal in patients receiving injection in all existing melanoma in phase II study PV-10-MM-02" was presented at the American Society of Clinical Oncology annual meeting (ASCO 2014) giving an analysis of patients receiving injection in all existing melanoma lesions during the Phase 2 trial. When all existing lesions were injected with PV-10, tumors were no longer detectable (complete response) in 50% of patients (Confidence Interval: 31-69%). This subgroup analysis supports the potential of PV-10 as a single agent and provides a rationale for a PV-10 Phase 3 randomized controlled trial in locally advanced melanoma patients.

  • In May 2014 a presentation entitled "Intralesional PV-10" on treating melanoma with intralesional PV-10 was given by Dr. Sanjiv S. Agarwala at the European Association of Dermato-Oncology Congress in Vilnius, Lithuania.

  • In March 2014 an application was submitted to the US FDA to receive Breakthrough Therapy Designation for PV-10 for treating melanoma.

  • In December 2013 a Type C meeting was held with the U.S. FDA's Division of Oncology Products 2. As a result of this meeting, Provectus will submit data from its Phase 2 study in a formal breakthrough therapy designation (BTD) request. The BTD request is expected to be submitted in the first quarter of 2014.

  • In September 2013 a poster presentation entitled "Locoregional Disease Control in Metastatic Melanoma: Exploratory Analyses From Phase 2 Testing of Intralesional Rose Bengal" was given at the European Cancer Congress 2013 in Amsterdam.

    The poster presentation highlighted mounting clinical and non-clinical evidence that PV-10 induces systemic immunologic activity. The clinical evidence includes: the inverse relationship of response to untreated tumor burden; the potential immune related adverse event of locoregional blistering; the strong correlation between objective response (OR) of target lesions and regression of untreated bystander lesions; and regression or stasis of untreated visceral disease in Stage IV subjects with OR of their injected target lesions. Non-clinical evidence cited by the researchers in support of systemic immunologic activity includes: synergy of PV-10 with anti-CTLA-4 therapy (presented at the AACR Annual Meeting 2013); and regression of synchronous flank and visceral tumors and adoptive transfer of immunity via T cells (PloS One 8, e68561, 2013).

  • In August 2013 the Moffitt Cancer Center issued a press release announcing that their first human clinical trial of PV-10 for advanced melanoma patients was in progress. In addition to monitoring the response of injected melanoma tumors, the study is also measuring the boost in the anti-tumor immune cells of patients after injection.

    In an initial study performed at Moffitt Cancer Center, researchers injected a single dose of PV-10 into mice with melanoma. The result was a significant reduction in the skin cancer lesions, as well as a sizable reduction in melanoma tumors that had spread to the lungs. The researchers said that PV-10 appeared to produce a robust anti-tumor immune response and may be safer than existing immunological agents. The initial study, Intralesional Injection of Rose Bengal Induces a Systemic Tumor-Specific Immune Response in Murine Models of Melanoma and Breast Cancer, was published in PLOS ONE in July 2013.

  • In July 2013 three presentations were made at the 8th World Congress of Melanoma discussing PV-10.
    • Researchers from The Centenary Institute, Newtown, Australia; and The University of Queensland Diamantina Institute, Woolloongabba, Australia presented research exploring the mechanism of action of Rose Bengal in a Free Communications session at the 8th World Congress of Melanoma in Hamburg. The presentation, titled "Rose Bengal - Phototoxicity versus Intrinsic Cytotoxicity", concludes that Rose Bengal in the absence of light induces autophagy in melanoma cells indicating a possible mechanism of action.
    • Dr. Sanjiv Agarwala of St. Luke's University Health Network gave a presentation entitled "Current perspectives on intralesional therapies" at a satellite symposium.
    • Professor John Thompson of the University of Sydney gave a presentation entitled "Limb perfusion / PV-10" as part of a symposium entitled "Loco regional melanoma treatment".
  • In July 2013, an article entitled "Intralesional Injection of Rose Bengal Induces a Systemic Tumor-Specific Immune Response in Murine Models of Melanoma and Breast Cancer" was published in PLOS ONE reports data establishing that IL PV-10 therapy induces tumor-specific T cell-mediated immunity in multiple histologic subtypes and support the concept of combining IL PV-10 with immunotherapy for advanced malignancies.
  • In April 2013, a poster presentation titled "Combination of PV-10 Immuno-chemoablation and Systemic Anti-CTLA-4 Antibody Therapy in Murine Models of Melanoma" was presented at the American Association of Cancer Research Annual Meeting. Results of these studies demonstrate that immuno-chemoablation with PV-10 is highly effective when all tumors are accessible for injection, providing rapid reduction of tumor burden and tumor-specific immunity. This work shows that addition of the immunologic effects of an anti-CTLA-4 agent, such as ipilimumab, augments the benefits of PV-10. For visceral or other inaccessible disease, combination of PV-10 with CTLA-4 blockade offers important potential for synergy.
  • In March 2013, Dr. Robert H. I. Andtbacka, Assistant Professor of Surgical Oncology, Huntsman Cancer Institute at the University of Utah, discussed PV-10 intralesional treatment of melanoma in a presentation titled "Current Status of Injectable Therapy" at the HemOnc Today - Melanoma and Cutaneous Malignancies Conference.
  • In October 2012, final top-line data from the Phase 2 trial of PV-10 for metastatic melanoma were presented at the ESMO (European Society for Medical Oncology) 2012 Congress by Dr. Sanjiv Agarwala in Poster Presentation III, Abstract #1137P, "Immuno-chemoablation of metastatic melanoma with intralesional rose bengal." Key results include:
    • An Objective Response Rate (OR) of 51% in subjects' target lesions (25% Complete Response and 26% Partial Response);
    • 69% disease control in these lesions (combined Complete, Partial and Stable Response subjects);
    • 33% of subjects having an untreated bystander melanoma lesion achieved an OR in their bystander lesions while 50% achieved disease control in these lesions;
    • Response of bystander lesions was highly correlated with outcome in treated target lesions, with a bystander lesion OR of 61% in subjects achieving complete or partial response in their target lesions versus 18% bystander lesion OR in subjects that did not achieve this level or response in their target lesions;
    • Stage III subjects experienced a substantially higher target lesion response rate (60% OR and 79% disease control) versus Stage IV subjects (22% and 33%, respectively);
    • Similar trends were noted in response metrics for bystander lesions between these two subpopulations;
    • Analysis of temporal data showed that Stage III subjects also experienced significantly greater mean Progression Free Survival (PFS) of at least 9.7 months, versus 3.1 months for Stage IV subjects (median PFS for Stage III subjects was not reached during the 12-month study interval);
    • Overall survival (OS) data were also presented by disease stage, with Stage III subjects achieving a mean overall survival of at least 12.6 months (median not reached during the study interval) versus 7.3 months for Stage IV subjects.
    • Case studies on several subjects illustrated potential stasis or regression of untreated visceral lesions following PV-10 treatment of their cutaneous lesions, while data on long-term treatment of one study participant demonstrated successful management of the disease over a period exceeding 3 years.

    Also at the presentation, further guidance was provided on the final design for the proposed Phase 3 Randomized Controlled Trial ("RCT") of PV-10 for metastatic melanoma. The study design is predicated on testing response of PV-10 in subjects most likely to derive clinical benefit from treatment of their cutaneous and subcutaneous melanoma lesions, specifically Stage III patients comparable to those investigated in the Phase 2 study. The design is anticipated to qualify as a pivotal trial under Special Protocol Assessment ("SPA") with the U.S. FDA. An SPA from the FDA is an agreement that the Phase 3 study design endpoints, statistical analyses and operational components of the planned clinical trials are acceptable to support approval of the product. Design parameters presented at ESMO include:
    • Approximately 180 subjects with Stage IIIB-IIIC melanoma, as supported by the Phase 2 response data;
    • Eligible subjects will have no active nodal disease (i.e., any involved nodes must have been excised prior to enrollment);
    • Subjects will be randomized 2 : 1 to PV-10 or systemic chemotherapy (dacarbazine or temozolomide);
    • In the PV-10 arm all cutaneous and subcutaneous lesions will be treated within the first two weeks, with additional treatment allowed every 14 days as necessary to achieve disease control;
    • In the chemotherapy arm standard 28 day dosing schedules will be used;
    • Clinical response will be assessed every 4 weeks, with full response assessment every 12 weeks, during the study interval;
    • Progression Free Survival (PFS) will serve as the primary endpoint, with progression defined to include increased tumor burden, advent of active nodal disease, onset of distant metastasis and symptomatic deterioration based on validated instruments.
    • The study duration is estimated to be approximately 30 months, with commencement expected in late 2012 or early 2013 following completion of review for SPA.
  • In June 2012, top-line data from the Phase 2 trial of PV-10 for metastatic melanoma were presented at the 2nd European Post-Chicago Melanoma Meeting 2012, Interdisciplinary Global Conference on Developing New Treatments for Melanoma by Dr. Sanjiv Agarwala. Key final data from the 80 subjects in the Phase 2 study include:
    • An Objective Response Rate (OR) of 50% in subjects' target lesions (25% Complete Response and 25% Partial Response);
    • 70% disease control in these lesions (combined Complete, Partial and Stable Response subjects);
    • 33% of subjects having an untreated bystander melanoma lesion achieved an OR in their bystander lesions while 50% achieved disease control in these lesions;
    • Response rates were analyzed by disease stage for the first time:
      • Stage III subjects experienced a substantially higher response rate (58% OR and 81% disease control) versus Stage IV subjects (22% and 33%, respectively);
      • Similar trends were noted in response metrics for bystander lesions between these two subpopulations;
      • Analysis of temporal data showed that Stage III subjects also experienced significantly greater mean Progression Free Survival (PFS) of at least 9.6 months, versus 3.1 months for Stage IV subjects. Median PFS for Stage III subjects was not reached during the 12-month study interval;
    • Higher response rates were noted among "evaluable subjects" (subjects that continued in the study for at least 8 weeks, enabling their responses to PV-10 to be assessed).
    The full presentation is available at:
    2nd European Post-Chicago Melanoma Meeting Munich, Germany - June 2012
  • In May 2012, in an article entitled "PV-10, aka Rose Bengal: Intralesional Therapy For Metastatic Melanoma", appearing on pages 5-7 in The Melanoma Letter, (Spring 2012, Vol. 30, No. 1), Sanjiv S. Agarwala, MD discusses the resurgence of intralesional therapies for melanoma and the especially intriguing "bystander" effect seen in Phase 2 studies of PV-10.
  • At the April 2012 HemOnc Today Melanoma and Cutaneous Malignancies meeting, in a presentation entitled " Update on Intralesional Ablative Therapies", Merrick I. Ross, MD gave an extensive overview of the latest results from clinical studies of intralesional agents for the treatment of metastatic melanoma, particularly those like PV-10 that are locally ablative with a systemic impact.

    Also in this session, a presentation entitled " Intralesional Therapy for Systemic Disease: Where Will it Fit in?" was presented by Robert H. I. Andtbacka, M.D., C.M, FACS, FRCSC. Dr. Andtbacka compares response rates for several intralesional melanoma drugs. The chart on slide 21, in particular, shows that PV-10 has a considerably better response rate in non-injected systemic lesions.
  • In March 2012, abstract #P265 entitled "Intralesional Injection of Melanoma with Rose Bengal Induces Regression of Untreated Synchronous Melanoma in a Murine Model," authored by P. Toomey, K. Kodumudi, L. Martin, A. Mackay, A. Sarnaik and S. Pilon-Thomas of the Moffitt Cancer Center was included in the Society of Surgical Oncology's 65th Annual Symposium Abstract Book and was published in Annals of Surgical Oncology, 2012; 19(1): S125. A poster presentation and detailed experimental data were presented during the Annual Meeting's melanoma poster session. In the study, an immune-mediated anti-tumor response to PV-10 treatment was observed, including induction of tumor-specific interferon-gamma production by splenocytes derived after PV-10 treatment compared to control.
  • In October 2011, Craig Dees, Ph.D. presented at the "2nd Annual Cancer Immunotherapy: a Long-Awaited Reality" conference, outlining preliminary results of method of action studies being conducted on animal models and evidence of an "immunotherapy-like" response witnessed in untreated tumors during Phase 1 and Phase 2 clinical trials of PV-10 for metastatic melanoma and liver cancer. Slides from Dr. Dees' presentation are available as a PDF document.
  • In June 2011, data was presented by two of Provectus's Principal Investigators for the Phase 2 melanoma study. Professor Merrick Ross, M.D., of the MD Anderson Cancer Center in Houston, Texas, gave a presentation entitled "Intralesional Therapy for Systemic Disease: Implications for Success and Failure," at the HemOnc Today Conference in New York City, providing a comprehensive review of modern intralesional therapies, including PV-10. A video containing slides and audio commentary of Dr. Ross' presentation is available on the HemOnc Today website.

    Dr. Sanjiv Agarwala, M.D., Chief of Medical Oncology and Hematology at St. Luke's Hospital and Health Network in Bethlehem, PA, gave a presentation entitled "Chemoablation of Metastatic Melanoma with PV-10" at the 7th EADO (European Association of Dermato-Oncology) Conference in Nantes, France. In his presentation, Dr. Agarwala reviewed Phase 2 data on PV-10 and outlined primary design parameters for a Phase 3 randomized controlled trial of PV-10, noting that the design is based on guidance obtained in meetings with the U.S. Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA).
  • Fully monitored study data for the entire study population of 80 subjects in the Phase 2 clinical trial of PV-10 for metastatic melanoma was presented by Dr. Sanjiv Agarwala at the 4th Interdisciplinary Melanoma & Skin Cancer Centres Meeting held at the Melanoma 2010 Congress in Sydney, Australia on November 4, 2010. A PDF document containing slides from the presentation, titled "Chemoablation of Metastatic Melanoma with PV-10", may be downloaded at PV-10_Presentation_Sydney-Nov-2010.pdf.
  • Additional positive data from the Phase 2 clinical trial of PV-10 for meastatic melanoma was presented at the ASCO 2010 Annual Meeting, Abstract #8534, entitled "Chemoablation of Metastatic Melanoma with Rose Bengal (PV-10)". The presentation poster and a video interview of Dr. Sanjiv Agarwala, Principal Investigator of the Phase 2 clinical study conducted at St. Luke's Hospital & Health Network in Bethlehem, PA, is available on the ASCO 2010 Presentation page.
  • An article entitled "A novel treatment for metastatic melanoma with intralesional rose bengal and radiotherapy: a case series", was published in the February 2010 issue of Melanoma Research. In the article, physicians involved with the Phase 2 clinical trial of PV-10 for metastatic melanoma observe an impressive response in patients receiving radiotherapy after previously being treated with PV-10.
  • Interim data on the first 40 subjects treated in the Phase 2 study of PV-10 for the treatment of metastatic melanoma were presented at the American Society of Clinical Oncology (ASCO) 2009 Annual Meeting, Abstract #9060, entitled "Chemoablation of melanoma with intralesional rose bengal (PV-10)". A video interview of Dr. Sanjiv Agarwala, Principal Investigator of the Phase 2 clinical study being conducted at St. Luke's Hospital & Health Network in Bethlehem, PA, as well as the poster from the ASCO 2009 presentation, is available on the ASCO 2009 Presentation page.
  • A paper entitled "Chemoablation of metastatic melanoma using intralesional Rose Bengal", based on the results of the Phase 1 study of intralesional PV-10 chemoablation in subjects with metastatic melanoma, was published in the December 2008 issue of Melanoma Research.
  • Professor John F. Thompson, MD presented interim results of the Phase 2 clinical trial of PV-10 for melanoma at the 6th International Symposium on Melanoma and Other Cutaneous Malignancies in March 2009.
  • Professor John F. Thompson, MD, Director of the Sydney Melanoma Unit, discussed ongoing clinical studies of melanoma treatments at the Sydney Cancer Conference 2008. Professor Thompson is the lead investigator for the Phase 2 clinical study of PV-10 for melanoma being conducted at the Sydney Melanoma Unit. A video and transcript of Professor Thompson's presentation at the SCC 2008 is available here.
  • A Phase 2 study of intralesional PV-10 in the treatment of metastatic melanoma, (study ID PV-10-MM-02), is currently in progress. The primary objective of this study is to investigate the effectiveness of intralesional (IL) PV-10 for locoregional treatment of metastatic melanoma. More details of the study are available at the U.S. National Institutes of Health ClinicalTrials.gov website.
  • A Phase 1 safety and tolerability study of intralesional PV-10 chemoablation in subjects with metastatic melanoma, (study ID PV-10-MM-01), has been completed. The objective of this study was to investigate the safety of intralesional (IL) PV-10 for the treatment of metastatic melanoma. This study also included a preliminary assessment of response of treated and untreated lesions by clinical evaluation at follow-up of 12 to 24 weeks following IL PV-10 treatment. Further details of this study are available at the U.S. National Institutes of Health ClinicalTrials.gov website.
  • A short animation is available that depicts PV-10 entering and destroying cancerous cells, while not entering or harming healthy cells.

Continue for further melanoma clinical trial information.

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