Detailed results presented last year at 2013 Annual Meeting of American Society of Clinical Oncology(ASCO) from a pivotal Phase III trial evaluating talimogene laherparepvec in patients with unresected stage IIIB, IIIC or IV melanoma compared to granulocyte-macrophage colony-stimulating factor (GM-CSF), showed a statistically significant difference in the the treatment of patients with regionally and distantly metastatic melanoma (stages III and IV), cancer has spread to skin, lymph nodes, or to other organs distant from the site of origin.[1][2]
Melanoma is a type of skin cancer that is characterized by the uncontrolled growth of melanocytes, which are the cells responsible for providing the pigment to skin. [3] Melanoma is the most aggressive and serious form of skin cancer. Currently, 132,000 melanoma cases occur globally each year. ]4] In the United States, while melanoma accounts for less than five percent of skin cancer cases, it causes the most skin cancer deaths. [4] The number of new cases of melanoma in the U.S. has been increasing for the last 30 years. [4]
Melanoma is considered to be advanced when it has spread, or metastasized, from the origin site to deeper parts of the skin or other organs such as the lymph nodes, lungs, or other parts of the body distant from the primary lesion site.[5]
“Over the last 30 years, the incidence of metastatic melanoma has increased by over 200%, so there is a need for new treatment options,” said study author Robert Andtbacka, M.D., assistant professor, University of Utah Huntsman Cancer Institute. “The results of a treatment with talimogene laherparepvecare encouraging in a disease as devastating as metastatic melanoma.”
The new investigational drug talimogene laherparepvec is an oncolytic immunotherapy designed to selectively replicate in tumor tissue and to initiate a systemic anti-tumor immune response. The drug is injected directly into tumor tissue and is intended to replicate preferentially in tumor cells causing lytic cell death.
Early evaluation of immunotherapeutic combinations is important in accelerating the development of new options for patients with cancer
Now Amgenand Merck, known as MSD outside the United States and Canada, have agreed to jointly evaluate the safety and efficacy of talimogene laherparepvec, an investigational oncolytic immunotherapy, combined with MK-3475, an investigational anti-PD-1 immunotherapy, in a Phase 1b/2 study of patients with mid- to late-stage melanoma.
One of the core reasons to investigate the benefits of the combination between these two investigational drugs is that many tumors are able to evade the immune system through a mechanism that exploits the PD-1 inhibitory checkpoint protein. MK-3475, is an highly selective anti-PD-1 immunotherapy designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system.
Monotherapy
“We are pleased to be collaborating with Amgen to study MK-3475 as part of this novel combination regimen,” said Dr. Eric Rubin, vice president, clinical development for oncology, Merck Research Laboratories. “Early evaluation of immunotherapeutic combinations is important in accelerating the development of new options for patients with cancer.”
Trial design
The multicenter, open-label clinical trial will be conducted in two parts and is planned to begin in the fall of 2014. Phase Ib is designed to determine the safety and tolerability of talimogene laherparepvec in combination with MK-3475 in patients with previously untreated, unresected, stage IIIB to IVM1a melanoma. The Phase II part of the trial is designed to evaluate efficacy, as assessed by the confirmed objective response rate (ORR), with talimogene laherparepvec in combination with MK-3475 versus MK-3475 alone in patients with previously untreated, unresected, stage IIIB to IVM1c melanoma. The study will further evaluate the efficacy of treatment with talimogene laherparepvec in combination with MK-3475 following disease progression on MK-3475 alone.
For information
[1] Andtbacka RHI, Collichio FA, Amatruda T, Senzer NN, Chesney J, Delman KA, et al. OPTiM: A randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma. J Clin Oncol 31, 2013 (suppl; abstr LBA9008)[Abstract][Meeting Slides]
[2] Single-arm Trial to Evaluate the Biodistirubtion and Shedding of Talimogene Laherparepvec -NCT02014441[Study Record Detail]
[3] National Cancer Institute, National Institute of Health, Dept. of Health and Human Services; What You Need to Know About Melanoma and Other Skin Cancers; June 2010.
[4] Ultraviolet radiation and the INTERSUN Programme. World Health Organization. Last accessed May 13, 2013. [Article]
[5] Melanoma Skin Cancer, American Cancer Society. Last accessed May 13, 2013.[Article]
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