Interim analysis of NCI Phase III study of Yervoy (ipilimumab) in high risk patients with stage III or resectable stage IV melanoma.- BMS

Bristol-Myers Squibb Company announced results of an interim descriptive analysis from an ongoing National Cancer Institute (NCI) Phase III randomized study evaluating Yervoy (ipilimumab) 3 mg/kg and Yervoy 10 mg/kg in patients with stage III or resectable stage IV melanoma who are at high risk of recurrence following complete surgical resection.

In this unplanned analysis of relapse-free survival (RFS) in concurrently randomized patients between the two experimental arms RFS at three years was 56% (n=367) for Yervoy 3 mg/kg (95% CI: 0.50, 0.61) and 54% (n=406) for Yervoy 10 mg/kg (95% CI: 0.49, 0.60). All-Cause Grade 3/4 adverse events (AEs) were experienced by 53% of patients in the Yervoy 3mg/kg arm (n=516) and 66% of patients in the Yervoy 10 mg/kg (n=503) arm. Treatment-related Grade 3/4 AEs were experienced by 37% and 57% of patients in the Yervoy 3mg/kg and 10 mg/kg arms, respectively. Treatment-related AEs led to discontinuation in 35% of patients taking Yervoy 3 mg/kg and 54% taking Yervoy 10 mg/kg. There were eight deaths in the Yervoy 10 mg/kg arm and two in the Yervoy 3 mg/kg arm that were considered at least possibly treatment-related. These data were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017.

E1609 is a Phase III study that enrolled 1,673 adult patients between May 2011 and August 2014 at multiple clinical sites, all belonging to the research groups in the NCI’s National Clinical Trials Network that design and lead trials focused on adult cancers: the Alliance for Clinical Trials in Oncology, ECOG-ACRIN Cancer Research Group, NRG Oncology, and SWOG. The study is comparing the effect of adjuvant Yervoy at either 3 mg/kg or 10 mg/kg versus high-dose interferon in adult patients with high-risk stage III or IV melanoma that has been removed by surgery. The study was not designed to compare the two Yervoy arms to each other. This analysis was performed to inform the effect of dose on efficacy and safety in the adjuvant setting. Co-primary endpoints of the study are overall survival and RFS comparing Yervoy versus high dose interferon alpha-2b. Secondary outcome measures include global quality of life and the safety profile of adjuvant Yervoy (10 mg/kg and 3 mg/kg) versus high-dose recombinant interferon alpha-2b. In this descriptive analysis, data was presented on the efficacy and safety of Yervoy 3 mg/kg and Yervoy 10 mg/kg at a median follow up of 3.1 years.

Adjuvant Therapy in Melanoma- Melanoma is separated into five staging categories (stages 0-4) based on the in-situ feature, thickness and ulceration of the tumor, whether the cancer has spread to the lymph nodes, and how far the cancer has spread beyond lymph nodes. Stage 3 melanoma has reached the regional lymph nodes but has not yet spread to distant lymph nodes or to other parts of the body (metastasized), and requires surgical resection of the primary tumor as well as the involved lymph nodes. Some patients may also be treated with adjuvant therapy, although adjuvant treatment options are very limited. Despite surgical intervention and possible adjuvant treatment, most patients experience disease recurrence and progress to metastatic disease. By five years, the majority of stage 3B and 3C patients (68% and 89%, respectively) and a third of stage 3A patients (37%) have experienced disease recurrence.