Bristol-Myers Squibb (BMY) Announces Strong Data from Yervoy Phase 3 vs. Placebo in Melanoma Patients

October 10, 2016 6:59 AM EDT

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Bristol-Myers Squibb Company (NYSE: BMY) announced superior efficacy with Yervoy 10 mg/kg versus placebo on all survival endpoints in the Phase 3 trial CA184-029 (EORTC 18071) evaluating stage III melanoma patients who are at high risk of recurrence following complete surgical resection. In the study, Yervoy compared with placebo significantly improved overall survival (OS) (HR=0.72 [95.1% CI: 0.58-0.88; p=0.001]), a secondary endpoint, with five-year OS rates at 65.4% in the Yervoy group and 54.4% in the placebo group. Distant metastasis-free survival (DMFS), a secondary endpoint, was also significantly improved versus placebo (HR=0.76 [95.8% CI: 0.64-0.92; p=0.002]) and had five-year DMFS rates of 48.3% and 38.9% in the Yervoy and placebo groups, respectively. In this updated five-year analysis, the recurrence-free survival (primary endpoint) benefit observed previously with Yervoy was maintained (HR=0.76 [95% CI: 0.64-0.89; p<0.001). The safety profile remained consistent with the initial analysis, with no new deaths or safety signals. The most common grade 3/4 immune-related adverse events in the Yervoy group were gastrointestinal (16.1%), hepatic (10.8%), and endocrine (7.9%).

These data were featured today, October 8, during the 2016 European Society for Medical Oncology Congress Press Program and simultaneously published in The New England Journal of Medicine. The data will also be presented today during a Presidential Symposium from 5:00-5:15 p.m. CEST (Abstract #LBA2_PR).

“Despite surgical intervention, most patients with stage III melanoma experience disease recurrence and progress to metastatic disease, reinforcing the unmet need for effective systemic therapies in the adjuvant setting,” said Alexander M.M. Eggermont, M.D., Ph.D., director general, Cancer Institute Gustave Roussy in Villejuif, France. “The impact of Yervoy on overall survival, distant-metastasis free survival, and recurrence-free survival observed in study -029 offers physicians new insights in the treatment of adjuvant melanoma.”

In stage III melanoma, the disease has not yet spread to distant lymph nodes or to other parts of the body and requires surgical resection of the primary tumor as well as the involved lymph nodes. The stage III patient population is heterogeneous with disease-specific survival rates of 78%, 59%, and 40% for stage IIIA, IIIB, and IIIC melanoma, respectively.

“The results from study -029 are important data for the scientific community and underscore our ongoing dedication to improving survival across stages of melanoma,” said Vicki Goodman, M.D., development lead, Melanoma and Genitourinary Cancers, Bristol-Myers Squibb. “Yervoy is the first immune checkpoint inhibitor to demonstrate a statistically significant survival benefit for high-risk patients with fully resected stage III melanoma. With further evaluation of our Immuno-Oncology agents and different dosing options, we remain committed to further research across the full continuum of melanoma treatment.”

About CA184-029 (EORTC 18071)

CA184-029 (EORTC 18071), a study initiated in 2008 by the European Organization for Research and Treatment of Cancer (EORTC), is a Phase 3, double-blind, placebo-controlled randomized trial evaluating the efficacy and safety of Yervoy 10 mg/kg in the adjuvant setting for high-risk stage III melanoma. The independently-run trial involved 99 centers across 19 countries from the EORTC’s pan-European network and specialized infrastructure. The trial enrolled eligible patients, which included those ≥18 years of age who underwent complete resection of stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis). In the trial, patients were randomized to receive Yervoy 10 mg/kg (n=475) or placebo (n=476) as an intravenous infusion every 3 weeks for 4 doses, followed by Yervoy 10 mg/kg or placebo every 12 weeks from Week 24 to Week 156 (three years), or until documented disease recurrence or unacceptable toxicity. Yervoy was studied across a broad range of patient characteristics, including patients with stage IIIa with lymph node >1 mm (20%), IIIb (44%) or IIIc with no in-transit metastases (36%); 42% had ulcerated primary lesions, and 58% had macroscopic lymph node involvement.

The primary endpoint was recurrence-free survival (RFS), defined as the time between the date of randomization and the date of first recurrence or death, as assessed by the Independent Review Committee. This analysis was the basis of the Yervoy approval in the United States for adjuvant treatment of melanoma at a dose of 10 mg/kg in October 2015. Secondary endpoints include overall survival (OS), distant metastases-free survival (DMFS), safety and health-related quality of life.

In the study, Yervoy significantly improved RFS, the primary endpoint, versus placebo across all patient groups. Updated five-year results demonstrated RFS remained significantly longer for Yervoy versus placebo, with a median RFS of 27.6 months (95% CI: 19.3-37.2) versus 17.1 months (95% CI: 13.6-21.6), respectively (HR=0.76; 95% CI: 0.64-0.89; p<0.001).

Yervoy also demonstrated a significant improvement in OS, a secondary endpoint of the study, with a 28% reduction in the risk of death versus placebo (HR=0.72 [95% CI: 0.58-0.88; p=0.001]) and an estimated five-year OS rate of 65.4% (95% CI: 60.8-69.6) for Yervoy versus 54.4% (95% CI: 49.7-58.9) for placebo. In addition, Yervoy showed a 24% reduction in the risk of developing distant metastases versus placebo (HR=0.76 [95.8% CI: 0.64-0.92; p=0.002]), with an estimated five-year DMFS rate of 48.3% with Yervoy versus 38.9% with placebo. The median DMFS was 48.3 months with Yervoy versus 27.5 months with placebo.

The safety profile of Yervoy based on this updated analysis was consistent with previously reported findings from CA184-029 (EORTC 18071). In those initial findings, five patient deaths occurred due to drug-related adverse events (AE); no new deaths have since been reported. Among the 471 patients who received Yervoy, 465 (98.7%) experienced an AE of any grade, and 255 patients (54.1%) experienced a grade 3 or 4 AE, whereas among 474 placebo-treated patients, 432 (91.1%) experienced an AE of any grade, and 124 patients (26.2%) experienced a grade 3 or 4 AE. Immune-related AEs were more frequent with Yervoy than with placebo. The most common grade 3/4 immune-related AEs in the Yervoy group were gastrointestinal (16.1%), hepatic (10.8%), and endocrine (7.9%). The median time to onset of on-study grade 2-5 immune-related AEs ranged from 4.0 weeks (skin immune-related adverse events) to 13.1 weeks (neurological immune-related adverse events). Endocrine grade 2-4 immune-related AEs resolved in 51.5% of patients, and median time to resolution was 54.3 weeks. The majority (82-97%) of all other grade 2-4 immune-related AEs resolved, and median time to resolution ranged from 4.0 to 8.0 weeks.

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