Data Demonstrated Metastatic Melanoma Response to Investigational Immunotherapy Ipilimumab
Tuesday June 5, 9:00 am ET
Clinical Phase I and II data presented at American Society of Clinical Oncology (ASCO) 2007 Annual Meeting
CHICAGO, June 5 /PRNewswire-FirstCall/ -- Medarex, Inc. (Nasdaq: MEDX - News) and Bristol-Myers Squibb Company (NYSE: BMY - News) today presented results from multiple clinical studies of ipilimumab (MDX-010), an investigational immunotherapy, for patients with advanced melanoma. The results demonstrated an anti-tumor response in some patients with advanced melanoma either as a monotherapy or in combination with other therapies. The results of the monotherapy study showed that 19% of patients (17/88) with advanced melanoma treated with ipilimumab experienced control of their disease, including tumor shrinkage and stabilization. The second presentation showed that complete or partial response was achieved in 13% of patients (46/356) with advanced melanoma when treated with ipilimumab alone or in combination with traditional chemotherapy (i.e., dacarbazine), interleukin-2, or a gp100 peptide vaccine. The results of this analysis also indicated that treatment with ipilimumab may take 12 weeks or longer to induce a response. These findings were presented at the American Society of Clinical Oncology's 2007 Annual Meeting in Chicago.
"In recent years, there have been limited advancements in the treatment of melanoma, particularly in the later stages of the disease," said Rachel Humphrey, MD, Vice President of Development at Bristol-Myers Squibb. "These studies represent an important advance in our understanding of how ipilimumab may work as a potential anti-cancer therapy for patients with this devastating disease."
(Abstract #8523) Results from a Phase II dose-escalation trial presented by Jeffrey S. Weber, MD, PhD, who was Chief of Oncology at the Keck School of Medicine at the University of Southern California at the time of the study, suggested that the anti-tumor response evolves over time in certain patients treated with ipilimumab. The primary endpoint of the study was to investigate the safety and clinical activity of various doses of ipilimumab. The study enrolled 88 patients with unresectable stage III or stage IV malignant melanoma in three cohorts receiving varying doses and regimens. Analysis of the data demonstrated:
- Overall disease control - defined as objective responses (complete and partial) and stable disease - achieved in 19% (17/88) of patients.
- In the cohort of 23 patients who were treated at 10 mg/kg, disease control was achieved in 39% (9/23), which lasted six months or longer in nearly all patients (8/9).
- Duration of disease stabilization or response exceeded six months in 15% (13/88) of patients. The longest effect observed (stable disease) is ongoing for more than a year.
Adverse events reported in this study were consistent with those immune- related adverse events (irAEs) results in other clinical trials of ipilimumab (diarrhea, rash, adrenal insufficiency, elevated liver enzymes). In this study, the overall incidence of irAEs was 72% (63/88). All patients who achieved a response (complete or partial responses) and most patients who achieved stable disease (12/13) also reported an irAE - primarily grade 1 or 2 with the exception of grade 3 diarrhea (1/88), adrenal insufficiency (1/88) and liver abnormalities (1/88) in three patients with stable disease. Twenty- eight percent (25/88) of patients reported serious adverse events (SAEs) regardless of causality, nine of which were ipilimumab-related, but not dose dependent. Most events were reversible without sequelae.
(Abstract #8525) Analysis of data aggregated from six Phase I and II trials, presented by Omid Hamid, MD, an investigator at The Angeles Clinic and Research Institute in Los Angeles, California, showed durable objective responses and stable disease in some patients who received varying doses of ipilimumab (0.1 up to 20 mg/kg, single or multiple doses) alone or in combination with dacarbazine, interleukin-2, or gp100 peptide vaccine. The primary endpoint of this analysis was to examine the kinetics of response to ipilimumab in 356 patients with stage III or stage IV metastatic melanoma; secondary endpoints included duration of objective response (defined as complete or partial response) and stable disease. Analysis of the kinetics of response data demonstrated:
- Complete or partial response achieved in 13% (46/356) of patients. Of these 46 patients:
- 61% (28/46) achieved an objective response at week 12 or later
- 35% (16/46) achieved stable disease prior to objective response (complete or partial)
- 22% (10/46) achieved a partial response, which developed into a complete response
- Current median duration of stable disease (from five of the six studies) was more than 15.4 weeks (median duration of objective response has not yet been reached). Twenty-five patients continue to respond with the longest response still ongoing at five years.
As previously reported for each individual study, the most common adverse events were immune-related (irAEs) including rash and diarrhea, which were medically manageable and reversible with treatment.
"In some cases, responses were achieved at 12 weeks or later in patients whose disease progressed after treatment with ipilimumab, suggesting that continued treatment through apparent disease progression may be beneficial," said Geoffrey M. Nichol, MBChB, Senior Vice President of Product Development at Medarex. "Further research is needed to fully understand how immunotherapies differ from currently approved chemotherapies." |
