In Phase I clinical trials, investigational drugs that target a protein known as PD-1 are showing promise for the treatment of advanced melanoma. Results from two of the trials were presented at the 2013 Annual Meeting of the American Society of Clinical Oncology and also published in the New England Journal of Medicine.
Of the more than one million new diagnoses of skin cancer each year, roughly 76,000 involve melanoma. More than 9,000 people die of melanoma each year in the United States. Melanoma is dangerous because it is more likely than other types of skin cancer to spread (metastasize) to other parts of the body.
PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 may enhance the ability of the immune system to fight cancer.
- 38% of patients had a response to treatment (tumor shrinkage)
- Patients who received the highest dose of lambrolizumab had a response rate of 52%
- Previous treatment with Yervoy® (ipilimumab) did not affect the response rate to lambrolizumab
- Responses tended to be durable (median duration had not yet been reached after 11 months of follow-up)
- Side effects tended to be mild and included fatigue, rash, itching, and diarrhea.
A separate Phase I study evaluated the investigational anti-PD-1 drug nivolumab in combination with Yervoy.[iii][iv]The study enrolled patients with inoperable Stage III or Stage IV melanoma who had received up to three prior therapies.
- Among patients who received concurrent treatment with the two drugs, the response rates were 21%, 53%, and 50% depending on the doses that were used (higher doses produced higher response rates).
- 31% of patients experienced tumor shrinkage of more than 80%.
- Responses tended to occur fairly quickly (within the first three months).
Although these are both early phase studies, the results are quite promising. Lambrolizumab and nivolumab each appear to have significant activity against advanced melanoma.
[i] Ribas A, Robert C, Daud A et al. Clinical efficacy and safety of lambrolizumab (MD-3475, Anti-PD-1 monoclonal antibody) in patients with advanced melanoma. Presented at the 49th Annual Meeting of the American Society of Clinical Oncology. May 31-June 4, 2013; Chicago, IL. Abstract 9009.
[ii] Hamid O, Robert C, Daud A et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. New England Journal of Medicine. Early online publication June 2, 2013.
[iii] Wolchok JD, Kluger HM, Callahan MK et al. Safety and clinical activity of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with advanced melanoma (MEL). Presented at the 49thAnnual Meeting of the American Society of Clinical Oncology. May 31-June 4, 2013; Chicago, IL. Abstract 9012.
[iv] Wolchok JD, Kluger HM, Callahan MK et al. Nivolumab plus Ipilimumab in Advanced Melanoma. New England Journal of Medicine. Early online publication June 2, 2013.