New Collaboration Leads to Combo Experimental Therapy for Metastatic Melanoma

“Pharmaceutical companies are teaming up to combine experimental therapies that may help combat metastatic cutaneous and uveal melanomas in a whole new way. The novel international collaboration may bring new combined targeted therapies to the market much sooner.

“Eli Lilly and Immunocore Limited are collaborating in immunotherapy-based clinical trials to evaluate the utility of Immunocore’s lead T-cell receptor-based investigational drug IMCgp100. This agent will be combined with Lilly’s galunisertib (LY2157299) and merestinib (LY2801653) for melanoma treatment. The investigators will explore the durability and efficacy of potential combined regimens in patients with metastatic cutaneous and uveal melanomas.

“ ‘Combining our ImmTAC, IMCgp100 with Lilly’s galunisertib and merestinib has the potential to transform the treatment of metastatic cutaneous and uveal melanoma. Immunocore is committed to the development of IMCgp100 in metastatic uveal and cutaneous melanoma where there is such great unmet medical need,’ said Eliot Forster, who is chief executive officer of Immunocore, Oxford, England.”


New Immunotherapy Yields Long-Lasting Responses in Some Patients with Advanced Melanoma

“A first-in-class immunotherapy called IMCgp100 yielded durable responses in patients with advanced cutaneous melanoma and those with advanced ocular melanoma, according to data from a phase I/IIa clinical trial presented here at the AACR Annual Meeting 2015, April 18-22.

” ‘IMCgp100 is a new type of immunotherapy that has two functional ends,’ said Mark R. Middleton, MD, PhD, professor of experimental cancer medicine at the University of Oxford in the United Kingdom. ‘The targeting end attaches to melanoma cells and the effector end locks on to any neighboring killer T cell [a type of immune cell], resulting in directed destruction of the tumor. One can think of IMCgp100 as a molecular bridge connecting melanoma cells with killer T cells, encouraging the killer T cells to destroy the melanoma cells.

” ‘Last year at the AACR Annual Meeting, we reported the results of the phase I dose-escalation portion of the clinical trial, which showed that IMCgp100 was well tolerated and had efficacy in some patients with advanced melanoma,’ continued Middleton. ‘This year, we are reporting data from 17 patients treated with the maximum tolerated dose of 600 nanograms of IMCgp100 per kilogram or an absolute dose of 50 micrograms of IMCgp100 as part of the phase I and phase IIa portions of the trial.’ “


PHP May Increase Survival in Patients with Liver Metastases

“Percutaneous hepatic perfusion increased hepatic progression free and overall survival rates in patients with liver metastases from melanoma vs. patients who underwent yttrium-90 therapy, according to data presented at the 2015 Society of Surgical Oncology Annual Cancer Symposium.

“Jonathan S. Zager, MD, FACS, director of regional therapies and chair of graduate medical education at Moffitt Cancer Center in Tampa, and colleagues, including Andrea M. Abbott, MD, of surgical oncology at Moffitt Cancer Center, analyzed data of 30 patients with cutaneous or uveal melanoma that metastasized to the liver after treatment with percutaneous hepatic perfusion (PHP), yttrium-90 (Y90) or chemoembolization using melphalan hydrochloride for injection with the Delcath Hepatic Delivery System (Melphalan/HDS, Delcath Systems, Inc.). The Melphalan/HDS is a system designed to supply high-dose chemotherapy to the liver while controlling systemic exposure, according to the Delcath website.”


Deep Fascia Excision No Help with Cutaneous Melanoma

“Excision of the deep fascia does not improve the outcome of patients with cutaneous melanomas thicker than 2 millimeters, according to a study published in the December issue of the British Journal of Dermatology.

“Robert E. Hunger, M.D., Ph.D., from the University of Bern in Switzerland, and colleagues retrospectively reviewed cases (1996 to 2012) of 213 patients (mean age, 62.6 years) with melanomas thicker than 2 millimeters who underwent excision with a 1-centimeter margin. Outcome comparisons were made between the fascia-excised and the fascia-preserved groups. Median follow-up was 1,547 days.

“The researchers found that the mean Breslow depth was 4.2 millimeters. There were no significant differences between the study groups in death attributable to melanoma, local recurrence, or locoregional and distant metastases. There were also no significant differences in disease-free or overall survival.”


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


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

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

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%.”


GSK's Melanoma Study Stopped Early on Survival Boost

The gist: In the U.S. and Australia, oncologists are allowed to prescribe a treatment that combines the drugs Mekinist (trametinib) and Tafinlar (dabrafenib) for people with unresectable or metastatic melanoma whose tumors have a V600E or V600K mutation in the BRAF gene. European regulators would like to see more data on the benefits and risks of the treatment before approving it for European patients. The company that produces the treatment was conducting a clinical trial with volunteer patients to capture that data, but has now decided to halt the trial, which was comparing the combo treatment to the drug Zelboraf (vemurafenib). The trial found that the combo treatment has such a significant improvement on patient survival that the patients who had been taking vemurafenib for comparison should be allowed to switch to the combo treatment, and the trial ended early.

“GlaxoSmithKline has stopped a Phase III study of its combination therapy for advanced cutaneous melanoma ahead of schedule after it showed a significant survival benefit.

“The UK drug giant said an Independent Data Monitoring Committee (IDMC) has made the recommendation as it emerged patients with metastatic melanoma – carrying a BRAFV600 mutation – who took a combo of Mekinist (trametinib) and Tafinlar (dabrafenib) demonstrated an overall survival benefit compared to those taking vemarufenib.

“Safety signals were also good, remaining consistent with that for the MEK inhibitor and BRAF inhibitor observed to date, the firm said.”


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

“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.