New Melanoma drug, Yervoy

"Yervoy" is a new name for ipilimumab (or short IPI) which has been discussed here a lot, especially today!

"Yervoy" is a new name for ipilimumab (or short IPI) which has been discussed here a lot, especially today!

Ipilimumab (also known as MDX-010 and Yervoy) is a human monoclonal antibody developed by Bristol-Myers Squibb and Medarex. It is used to activate the immune system. I believe it will be given as it was in the trials as a intravenous solution, one dose every 3 wks for a total of 4 doses. 

Ipilimumab binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that is believed to play a critical role in regulating natural immune responses. The absence or presence of CTLA-4 can augment or suppress the immune system's T-cell response in fighting disease. Ipilimumab is designed to block the activity of CTLA-4, thereby sustaining an active immune response in its attack on cancer cells.

Here is a link to a study which shows the response rate and side effects. 

From: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70334-1/abstract

February, 2010.

Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomized, double-blind, multicentre, phase 2, dose-ranging study.

 Findings:

 The best overall response rate was 11.1% for 10 mg/kg, 4.2% for 3 mg/kg, and 0% for 0·3 mg/kg. Immune-related adverse events of any grade arose in 50 of 71, 46 of 71, and 19 of 72 patients at doses of 10 mg/kg, 3 mg/kg, and 0·3 mg/kg, respectively; the most common grade 3—4 adverse events were gastrointestinal immune-related events (11 in the 10 mg/kg group, two in the 3 mg/kg group, none in the 0·3 mg/kg group) and diarrhea (ten in the 10 mg/kg group, one in the 3 mg/kg group, none in the 0·3 mg/kg group). 

I have also read on other sites that side effects occur in up to 84% of patients and the most common side effects of ipilimumab occur in the gastrointestinal tract (such as diarrhea and inflammation of the colon) and the skin (such as rash and inflammation of the skin). Less frequently occurring side effects include hepatitis, inflammation of the pituitary gland (hypophysitis), eye inflammation (uveitis), and kidney problems (nephritis).

In another study:

http://knol.google.com/k/krishan-maggon/ipilimumab-bms-review-a-cancer/3fy5eowy8suq3/107# 

In a Phase II trial in 155 patients with pretreated stage III or stage IV melanoma, the best overall response rate (modified WHO criteria) was 5.8% short of 10% minimum required by FDA. The disease was controlled in 27% of patients treated with 10 mg/kg induction (4 cycles) and maintenance doses. The survival at 1 year was 47% and at 2 year 33%. Forty three patients had progressive disease. Adverse drug reactions were immune related, 19% patients had Grade 3 and 3.2% Grade 4 dermatological and gastrointestinal toxicity. In a compassionate use trial in MSKC in advanced refractory patients, 53 patients were enrolled and 51 were eligible for analysis. grade 3 toxicity was reported by 29% of patients, 12% of patients had tumor response (CR+PR) and 29% had stable disease. Overall survival in this group was 7.2 months and progression free survival was 2.6 months.

Michael

Ipilimumab (also known as MDX-010 and Yervoy) is a human monoclonal antibody developed by Bristol-Myers Squibb and Medarex. It is used to activate the immune system. I believe it will be given as it was in the trials as a intravenous solution, one dose every 3 wks for a total of 4 doses. 

Ipilimumab binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that is believed to play a critical role in regulating natural immune responses. The absence or presence of CTLA-4 can augment or suppress the immune system's T-cell response in fighting disease. Ipilimumab is designed to block the activity of CTLA-4, thereby sustaining an active immune response in its attack on cancer cells.

Here is a link to a study which shows the response rate and side effects. 

From: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70334-1/abstract

February, 2010.

Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomized, double-blind, multicentre, phase 2, dose-ranging study.

 Findings:

 The best overall response rate was 11.1% for 10 mg/kg, 4.2% for 3 mg/kg, and 0% for 0·3 mg/kg. Immune-related adverse events of any grade arose in 50 of 71, 46 of 71, and 19 of 72 patients at doses of 10 mg/kg, 3 mg/kg, and 0·3 mg/kg, respectively; the most common grade 3—4 adverse events were gastrointestinal immune-related events (11 in the 10 mg/kg group, two in the 3 mg/kg group, none in the 0·3 mg/kg group) and diarrhea (ten in the 10 mg/kg group, one in the 3 mg/kg group, none in the 0·3 mg/kg group). 

I have also read on other sites that side effects occur in up to 84% of patients and the most common side effects of ipilimumab occur in the gastrointestinal tract (such as diarrhea and inflammation of the colon) and the skin (such as rash and inflammation of the skin). Less frequently occurring side effects include hepatitis, inflammation of the pituitary gland (hypophysitis), eye inflammation (uveitis), and kidney problems (nephritis).

In another study:

http://knol.google.com/k/krishan-maggon/ipilimumab-bms-review-a-cancer/3fy5eowy8suq3/107# 

In a Phase II trial in 155 patients with pretreated stage III or stage IV melanoma, the best overall response rate (modified WHO criteria) was 5.8% short of 10% minimum required by FDA. The disease was controlled in 27% of patients treated with 10 mg/kg induction (4 cycles) and maintenance doses. The survival at 1 year was 47% and at 2 year 33%. Forty three patients had progressive disease. Adverse drug reactions were immune related, 19% patients had Grade 3 and 3.2% Grade 4 dermatological and gastrointestinal toxicity. In a compassionate use trial in MSKC in advanced refractory patients, 53 patients were enrolled and 51 were eligible for analysis. grade 3 toxicity was reported by 29% of patients, 12% of patients had tumor response (CR+PR) and 29% had stable disease. Overall survival in this group was 7.2 months and progression free survival was 2.6 months.

Michael