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百时美施贵宝黑色素类药物Yervoy III期达主要终点

  1. Yervoy
  2. 百时美施贵宝
  3. 辅助治疗
  4. 黑色素瘤

来源:生物谷 2014-06-04 09:18

百时美施贵宝黑色素瘤药物Yervoy III期研究达主要终点,该研究调查了Yervoy作为辅助疗法用于预防或推迟已切除黑色素瘤的复发,研究达到了无复发生存的主要终点。

2014年6月4日讯 /生物谷BIOON/ --百时美施贵宝(BMS)6月2日公布了黑色素瘤药物Yervoy(ipilimumab,易普利姆玛)一项III期研究CA184-029 (EORTC 18071) 的积极数据。该项研究评估了Yervoy 10mg/kg剂量作为辅助疗法,用于预防或推迟已完全切除高危III阶段黑色素瘤病情复发的疗效。数据表明,在治疗的3年中,Yervoy治疗组有46.5%的患者病情无复发,安慰剂组为34.8%(p=0.0013);同时,Yervoy治疗组无复发生存期(RFS)为26.1个月,安慰剂组为17.1个月,平均随访期为2.7年,达到了研究的主要终点。目前,调查Yervoy用于辅助治疗的其他试验正在进行中,包括调查3mg/kg和10mg/kg剂量的一项III期研究。

Yervoy是一种重组人单克隆抗体,阻断细胞毒性T淋巴细胞相关抗原4(CTLA-4)。CTLA-4是一种T细胞活化的负调控因子,Yervoy与CTLA-4结合后,能阻断CTLA-4与其配体CD80/CD86的相互作用。阻断CTLA-4已被证明能够增强T细胞的活化和增殖。Yervoy在黑色素瘤患者中的疗效作用机制,是间接通过T细胞介导的抗肿瘤免疫反应。FDA于2011年3月批准Yervoy 3mg/kg单药疗法用于不能手术切除或转移性黑色素瘤患者的治疗,目前该药已获全球40多个国家批准。(生物谷Bioon.com)

英文原文:Phase 3 Study Evaluating Yervoy® (Ipilimumab) for Melanoma in an Adjuvant Setting Meets Primary Endpoint of Recurrence-Free Survival

Results demonstrate a significant improvement in recurrence-free survival for an investigational dose of Yervoy vs. placebo for patients with stage 3 melanoma at high risk of recurrence following surgical resection

Types of adverse events were generally consistent with those observed using Yervoy in advanced melanoma, although a higher incidence of endocrinopathies was observed

Third positive Phase 3 trial of Yervoy in melanoma, now with a study demonstrating efficacy in an earlier stage of the disease

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced results from a Phase 3 randomized, double blind study demonstrating that Yervoy (ipilimumab) 10 mg/kg (n=475) significantly improved recurrence-free survival (RFS, the length of time before recurrence or death) vs. placebo (n=476) for patients with stage 3 melanoma who are at high risk of recurrence following complete surgical resection, an adjuvant setting. A twenty-five percent reduction in the risk of recurrence or death was observed (HR = 0.75; 95% CI = 0.64–0.90; p = 0.0013). At three years, an estimated 46.5% of patients treated with Yervoy were free of disease recurrence compared to an estimated 34.8% of patients on placebo. The median RFS was 26.1 months for Yervoy vs. 17.1 months for placebo, with a median follow-up of 2.7 years. The data will be presented at the 50th Annual Meeting of the American Society of Clinical Oncology at 3:00 p.m. CDT today and highlighted at a Congress press briefing (LBA9008).

Treatment-related adverse events were common, with most being immune-related, and were managed using standard Yervoy adverse event (AE) management protocols. These Grade ≥3 AEs in the Yervoy and placebo arms, respectively, were gastrointestinal (15.9% vs. 0.8%), liver (10.6% vs. 0.2%), endocrine (8.5% vs. 0%) and dermatologic (4.5% vs. 0%). Most were managed and resolved using established algorithms. Per investigator assessment, the incidence of drug-related death in the Yervoy arm was 1.1% (n=5) and no drug-related deaths were observed in the placebo arm. Of the patients who began treatment with Yervoy (n=471), 48.8% (n=230) discontinued treatment due to drug-related AEs vs. 1.7% (n=8) in the placebo arm.

“Despite the strong likelihood of disease recurrence among stage 3 melanoma patients, there are very limited treatment options available to help reduce the risk of metastatic disease after surgery. There is only one class of therapies available to patients and this standard of care has remained largely unchanged over the last 20 years,” said Alexander Eggermont, director general, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France, presenter of the results and lead author of the abstract. “These findings are significant not only because ipilimumab is the first immune-checkpoint inhibitor to demonstrate an improvement in recurrence-free survival in this earlier treatment setting, but also because this benefit was observed across all patient sub-groups, including those who were at highest risk of recurrence. These findings add to the growing body of data for ipilimumab, which is currently approved at 3 mg/kg for metastatic melanoma.”

“This is the third positive Phase 3 trial of Yervoy in melanoma, reflecting our commitment to seeking options to address unmet medical needs across stages of disease and lines of therapy for melanoma,” said Michael Giordano, senior vice president, Head of Development, Oncology & Immunosciences, Bristol-Myers Squibb. “These findings demonstrate, for the first time, that Yervoy has the potential to reduce the risk of cancer recurrence at an earlier stage of melanoma and support our belief that immuno-oncology may have broad applicability across lines of therapy and stages of the disease.”

Additional trials of Yervoy for melanoma in the adjuvant setting are ongoing, including a Phase 3 study sponsored by the U.S. National Cancer Institute and conducted by ECOG-ACRIN investigating Yervoy at doses of 3 mg/kg and 10 mg/kg, or high-dose interferon alfa-2b in patients with high-risk stage 3 and resectable stage 4 melanoma.

About Study -029

CA184-029 (EORTC 18071) is a randomized, double-blind Phase 3 trial sponsored by Bristol-Myers Squibb and conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC), assessing the efficacy of Yervoy at the investigational dose of 10 mg/kg in preventing or delaying recurrence after complete resection of high-risk Stage 3 melanoma. The trial enrolled patients in the United States, Canada, Europe, Russia and Australia who underwent complete resection of stage 3 cutaneous melanoma, excluding lymph node metastasis ≤1 millimeter or in-transit metastasis. Patients had stage 3A (21%), 3B (45%) or 3C (35%) melanoma; 41% percent had ulcerated primary melanoma and 56% had macroscopic lymph node involvement. Patients were stratified by stage and region and were randomized 1:1 to receive Yervoy 10 mg/kg (n=475) or placebo (n=476) every 3 weeks for 4 doses, then every 3 months for up to 3 years until completion, disease recurrence, or unacceptable toxicity. The primary endpoint was recurrence-free survival, analyzed on the intent-to-treat population.

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.

About Yervoy

Yervoy, which is a recombinant, human monoclonal antibody, blocks the cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of Yervoy’s effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses. On March 25, 2011, the FDA approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is now approved in more than 40 countries.

There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types. This includes Phase 3 trials in prostate and lung cancers.

YERVOY® (ipilimumab) INDICATION & IMPORTANT SAFETY INFORMATION

YERVOY (ipilimumab) is indicated for the treatment of unresectable or metastatic melanoma.

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