How to Treat Melanoma:
Current Landscape and Options
Today, melanoma is one of the most dangerous forms of skin cancer and late-stage melanoma accounts for the vast majority of skin cancer deaths. Following diagnosis, patients are often overwhelmed by the amount of information that is available to them regarding treatment options, therapy centers, and new terminology.
The treatment landscape in melanoma is constantly evolving and scientists are finding safer and more effective treatments that have long term benefits for melanoma patients. To help summarize this information, the following is a brief overview of melanoma survival rates, treatment options, and new approaches.
Survival rates for patients in the United States vary depending on the stage of cancer and when the patient is diagnosed. For early-stage melanoma (e.g., Stage I and/or II non-metastatic), surgical excision can be curative in a majority of cases. The overall five-year survival rate for patients with such localized melanoma is 98 percent in the United States.(1)
At later stages, malignant melanoma remains deadly and difficult to treat cancer. The overall five-year survival rate is 63 percent in the United States when the cancer is detected in the lymph nodes; and, declines to 16 percent when the cancer has metastasized to distant organs.
Melanoma that has metastasized to distant organs and tissues has traditionally been treated with a combination of surgery, chemotherapy and/or radiation therapy. Numerous chemotherapy regimens have been tested in melanoma with only modest success and limited overall survival benefit.(2)
Immunotherapy, which harnesses the body’s immune system to fight cancer, has been an effective treatment for patients with certain types of cancer that have been previously resistant to chemotherapy and radiation treatment, such as melanoma. The emergence of two new approaches in immunotherapy – checkpoint inhibitors and targeted kinase inhibitors – have demonstrated improvement in overall survival of patients when compared to traditional chemotherapy.(2)
While immunotherapy can be extremely effective, the currently marketed therapies do not benefit the majority of patients. While checkpoint therapies can produce durable responses, 70-80% of patients do not respond to this type of immunotherapy. This non-responder population represents a large unmet medical need in oncology.
A New Approach
Today, scientists are working on improving immunotherapies by combining them with other types of cancer treatments to improve response rates. This combination approach may increase the number of patients that can benefit from these revolutionary therapies. Early data from clinical trials evaluating these combination approaches are promising. Researchers also continue to focus efforts on targeting pathways of various immune cell activation.(3) One such approach relies on the correlation of a type of immune cell presence in a tumor with improved prognosis and long-term survival.(4,5) This cell type, known as a CD8+ T cell, is an immune cell that can recognize and kill cancer cells. Many emerging experimental immunotherapies are seeking to increase the anti-tumor CD8+ T cell response, resulting in increased immunogenicity of the tumor.
Addressing the Unmet Medical Need
OncoSec Medical Incorporated is developing combination approaches for melanoma and believes to be one step closer to providing an innovative immunotherapy option for patients. OncoSec is developing immune-stimulating therapies that can convert ‘T-cell poor’ (cold) tumors to ‘T-cell rich’ (hot) tumors by driving immune cells into the tumor and stimulating anti- cancer immune activity. By increasing T-cells at the tumor site, these therapies appear to prime the immune system for improved response to checkpoint inhibitors.
In OncoSec’s Phase II investigational therapy trial, ImmunoPulse® IL-12 in combination with Merck's approved checkpoint inhibitor therapy, Keytruda® (also known as pembrolizumab), showed 48% of patients with advanced melanoma had a best overall response rate in patients with cold tumors. This is in comparison to a 33% response rate with KEYTRUDA alone, typically in patients that already have hot tumors.
Based on previous positive clinical data, the US Food and Drug Administration (FDA), granted OncoSec Fast Track designation. Fast Track designation is an expedited review granted by the agency to facilitate the development of drugs which treat a serious or life-threatening condition and fill an unmet medical need. Based on this designation, OncoSec is initiating a registration- directed trial focusing on patients that fail on Keytruda®, Opdivo® or combination of Opdivo®- Yervoy®. This is a Phase II, open label, multicenter study of ImmunoPulse® IL-12 in combination with a checkpoint inhibitor therapy in patients with Stage III or IV melanoma that cannot be surgically removed.
OncoSec is helping to pioneer combination approaches in the melanoma space and may be the first biopharma company to receive accelerated approval to help address the large population of patients who do not respond to current checkpoint inhibitor therapies. OncoSec is hoping to improve understanding of how different therapeutics can work better together to expand the number of safer and more effective combinations. It is the team’s goal to help improve outcomes for melanoma patients and provide hope for patients suffering from late-stage melanoma.
1. American Cancer Society. Cancer Facts & Figures.
2. National Cancer Institute. Melanoma Treatment for Health Professionals.
3. Thomas, N. E., et al. (2013). "Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study." J Clin Oncol 31(33): 4252-4259.
4. Dudley, M. E., et al. (2005). "Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma." J Clin Oncol 23(10): 2346-2357.
5. Hunder, N. N., et al. (2008). "Treatment of metastatic melanoma with autologous CD4+ T cells against NY- ESO-1." N Engl J Med 358(25): 2698-2703.