Melanoma: New Drugs and New Challenges (Part 2 of 2)


Written by Emma Shtivelman, PhD

Editor’s note: This is part 2 of a 2-part post on the latest research in melanoma. To learn about research into drug combinations for melanoma that may work better than single drugs, check out Melanoma: New Drugs and New Challenges (Part 1 of 2).

As always, the more new treatments become available in melanoma, the more new challenges arise. With eight new drugs approved for melanoma in the last five years, oncologists may sometimes face the difficult choice of what drugs to choose for a patient’s first-line treatment. Immune checkpoint drugs sometimes cause serious side effects, but progress is being made on how to treat these and also how to treat patients with pre-existing autoimmune conditions. New approaches are needed in efforts to prevent recurrence of melanomas diagnosed at earlier stages of disease progression. These and other challenges are discussed below. Continue reading…

Phase 3 Trial to Compare PV-10 with Chemotherapy in Stage III Melanoma

Healio | Apr 10, 2015

“Recruitment will begin soon for a phase 3 trial that will compare intralesional PV-10 with chemotherapy in patients with stage IIIb or IIIc melanoma, according to a presenter at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.

“The analysis will include 225 patients. Two-thirds will be randomly assigned to monthly injections with PV-10 (Provectus), a sterile, non-pyrogenic solution of rose bengal disodium that destroys tumors by necrosis. The other patients will be assigned standard-dose chemotherapy with dacarbazine or temozolomide.

“All patients must have cutaneous and subcutaneous disease with no active nodal disease, and all lesions must be BRAF wild type. All patients must be either refractory to or not candidates for systemic immunotherapy.

“ ‘This is a trial design that is difficult to do,’ Sanjiv S. Agarwala, MD, chief of oncology and hematology at St. Luke’s Cancer Center, professor at Temple University School of Medicine and a HemOnc Today Editorial Board member, said during a presentation. ‘We’re going to need a lot of centers, and there will be smaller groups per center because these are not easy patients to find. But we’re not going to deprive patients of the ability to get checkpoint inhibitors if that is the right treatment for them.’ ”

Advanced Melanoma: The Promise and Shortcomings of Drugs Injected Directly into Tumors


Written by Emma Shtivelman, PhD

In the past 3 years, the treatment landscape for metastatic melanoma has changed dramatically. We saw the advent of drugs that inhibit mutant BRAF and activate MEK proteins (vemurafenib, dabrafenib, and trametinib) and drugs known as immune checkpoint inhibitors (ipilimumab, Keytruda, Opdivo, and others). These treatments are ‘systemic’; that is, they are taken by mouth or injected directly into the bloodstream and spread throughout the body. However, as I reported earlier this year, drugs that are injected directly into tumors—’intralesional drugs’—have recently gained some attention. Two of them were featured at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting. New data, and doubts, on these drugs have since emerged. Continue reading…

Updated: New Melanoma Drug Shows Promise In Trial, But Questions About Effectiveness Remain

Forbes | Oct 29, 2014

The gist: Earlier this month we posted about promising results from a clinical trial testing a new treatment called PV-10. Now, an oncologist who was not involved in the research has told a Forbes reporter that the results may not be as promising as they sound.

“A new cancer drug benefited 51% of stage III and IV melanoma patients during a phase II trial, achieving complete response (total cancer disappearance) in 26% during the treatment period. That was all in just 16 weeks of treatment, and would seem to suggest this drug, being developed by a small company ignored by Wall Street, has potential for treating certain cancers in the future.

“But an independent oncologist not associated with the trial says that the results may not be so impressive after all, based on the data from the published study.

“John Glaspy, an oncology professor at UCLA, says that ‘it’s not clear’ whether the result are important. If they are talking about lesions that were not directly injected with the drug, the results would be meaningful. ‘If they are talking about the injected lesion, not so much,’ Glaspy says.

“When asked about it, he repeated: ‘Like I said, these SQ melanomas are an indolent disease, and it is not a big deal if you inject them and they regress.  I don’t think you have any evidence that anybody is cured.’ “

PV-10 Well-Tolerated in Treatment of Refractory Cutaneous Melanoma

Healio | Oct 8, 2014

The gist: A new treatment has shown early promise for treating people with cutaneous melanoma that worsened after previous treatment. The new treatment involves injecting a substance called rose bengal disodium into melanoma lesions. It was tested in volunteer patients in a recent clinical trial. The treatment proved safe, and 51% of the patients experienced a good response.

“Intralesional injection of rose bengal disodium was well-tolerated in patients with refractory cutaneous melanoma, with just over half of patients meeting the primary study endpoint, according to a poster presented at the European Society of Medical Oncology Annual Congress.

“Researchers included 80 patients with 6.3-cm median sum lesion diameter in biopsy-confirmed melanoma that was refractory to a median of six previous interventions in the study. The patients received intralesional injections of rose bengal disodium (PV-10) in up to 20 cutaneous and subcutaneous lesions up to four times during a 16-week period. Follow-up was 52 weeks.

“The researchers assessed best overall response rate (BORR) in up to 10 injected target lesions, and secondary endpoints included the assessment of response duration, BORR of untreated bystander lesions, overall survival and adverse events.

“PV-10 was found to be well-tolerated, and 41 patients achieved the study’s primary endpoint of an objective response for an overall response rate of 51%.”

PV-10 Produced Complete Response in 50% of Advanced Melanoma Patients

Medical News Today | Jun 10, 2014

“Half of patients with locally advanced cutaneous melanoma who had all their lesions injected with the investigational agent PV-10 achieved a complete response in a phase 2 study, according to a presentation at the 50th American Society of Clinical Oncology meeting, held in Chicago, IL, May 30th to June 2nd.”

Editor’s note: PV-10 is a new drug that can be injected directly into a cutaneous melanoma tumor. In a recent clinical trial testing the drug on volunteers, half of all patients who had all of their tumors injected experienced complete disappearance of their tumors.

Induction of Systemic Immunity Following Treatment of Tumors with PV-10 Reported by Moffitt Cancer Center Researchers at American Association for Cancer Research Annual Meeting

Provectus Biopharmaceuticals | Apr 7, 2014

“Provectus Biopharmaceuticals, Inc. (OTCQB: PVCT, http://www.pvct.com), a development-stage oncology and dermatology biopharmaceutical company, announced today that a poster presentation detailing significant decrease in melanoma cells in patients’ injected tumors 7-14 days after intralesional PV-10 treatment that was accompanied by similar decrease in uninjected bystander tumors was presented April 6 by researchers from the Moffitt Cancer Center at the American Association for Cancer Research Annual Meeting in San Diego, CA. These clinical and pathologic changes were accompanied by increases in important immune cell populations detected in the patients’ peripheral blood.”

Editor’s note: This story is about a new treatment called PV-10 that is injected directly into melanoma tumors. A clinical trial to test the drug in people with melanoma has shown promising results. The manufacturers of the drug have submitted an application for “breakthrough therapy” designation from the U.S. Food and Drug Administration (FDA) to expedite the FDA-approval process and rapidly make the drug available to many more melanoma patients in the U.S.

Will PV-10 Injections Shrink Melanomas in People, Too?

ASCO Post│Aug 28, 2013

A new phase I clinical trial is underway to see if an experimental melanoma treatment works as well in people as it does in mice. The treatment entails injecting tumors with PV-10. A previous study in mice showed that just one PV-10 injection was enough to  shrink melanomas. In addition, very early trials suggested that PV-10 boosts the immune system and the mouse study suggested that this treatment has fewer side effects than current immunotherapies. The new trial will assess whether PV-10 shrinks melanomas and keeps them from spreading in people, as well as whether PV-10 actually boosts the immune system. This trial is currently accepting participants.

Single Injection of PV-10 Being Tested in the Treatment of Advanced Melanoma

The ASCO Post. Aug 28, 2013.

“A new study underway at Moffitt Cancer Center in Tampa, Florida, is investigating whether an intralesional injection of PV-10 (a substance derived from Rose Bengal, a staining agent that has been used to assess eye damage), is effective in reducing tumors and the spread of cancer in patients with melanoma. Early clinical trials show PV-10 can boost immune response in melanoma tumors and in the bloodstream.”