Merck’s KEYTRUDA® (pembrolizumab) Reduced the Risk of Disease Recurrence or Death by More than 40 Percent Compared to Placebo as Adjuvant Therapy in Resected, High-Risk Stage III Melanoma

KEYTRUDA is First Anti-PD-1 Therapy to Show Recurrence-Free Survival (RFS) Benefit Across Stage IIIA (> 1 mm Lymph Node Metastasis), IIIB and IIIC Melanoma

EORTC1325/KEYNOTE-054 Results Presented Today in Opening Plenary at AACR 2018 and Published in The New England Journal of Medicine

KENILWORTH, NJ, USA & BRUSSELS, Belgium I April 15, 2018 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, and the European Organisation for Research and Treatment of Cancer (EORTC), today announced findings from the Phase 3 EORTC1325/KEYNOTE-054 trial investigating KEYTRUDA®, Merck’s anti-PD-1 therapy, as adjuvant therapy in resected, high-risk stage III melanoma. Study results showed KEYTRUDA significantly prolonged recurrence-free survival (RFS), reducing the risk of disease recurrence or death by 43 percent compared to placebo in the overall study population (HR=0.57 [98.4% CI, 0.43-0.74]; p<0.0001). For the primary endpoint of RFS in the overall study population, the one-year RFS rate was 75.4 percent (95% CI, 71.3-78.9) for KEYTRUDA compared to 61.0 percent (95% CI, 56.5-65.1) for placebo. For the co-primary endpoint of RFS in patients whose tumors were considered PD-L1 positive, KEYTRUDA demonstrated significantly prolonged RFS compared to placebo (HR=0.54; 95% CI, 0.42-0.69; p<0.0001). The safety profile of KEYTRUDA was consistent with what has been seen in previous trials among patients with advanced melanoma. These results are being presented today for the first time in the opening plenary session at the American Association for Cancer Research (AACR) Annual Meeting 2018 (Abstract #10526), with simultaneous publication in The New England Journal of Medicine.

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“The EORTC is very pleased to have collaborated with Merck on this important study which showed a significant recurrence-free survival benefit across all stage III melanoma,” said Alexander Eggermont, study chair, director general at the Gustave Roussy Cancer Institute, professor of oncology, University of Paris-Saclay.

“These data demonstrate compelling evidence that adjuvant treatment with KEYTRUDA provides significant recurrence-free survival benefit after surgery in patients with high-risk Stage III melanoma,” said Roy Baynes, M.D., Ph.D., senior vice president and head of Global Clinical Development, chief medical officer, Merck Research Laboratories. “These are the first data for KEYTRUDA in the adjuvant setting and mark an important advancement for the treatment of resected stage III melanoma. We are pleased to be sharing these data with global regulatory authorities.”

KEYTRUDA is the first anti-PD-1 therapy to show RFS benefit across stage IIIA (> 1 mm lymph node metastasis), IIIB and IIIC melanoma. The RFS benefit was also seen regardless of BRAF mutation status (HR=0.64 [99% CI, 0.42-0.96] for patients with wild-type BRAF status; HR=0.57 [99% CI, 0.37-0.89] for patients with mutant BRAF status). As previously announced, Merck is working to submit data from EORTC1325/KEYNOTE-054 to regulatory agencies in the U.S. and around the world.

“As an organization dedicated to eliminating melanoma suffering and death, we are thrilled to see these important new data on KEYTRUDA,” said Louise M. Perkins, Ph.D., chief science officer, Melanoma Research Alliance. “The ability to significantly prevent melanoma from coming back after surgery, along with a demonstrated safety profile, makes this a welcome development in the fight against melanoma.”

Merck has a broad clinical development program in melanoma with KEYTRUDA as monotherapy and in combination with other novel mechanisms. The program, which is comprised of more than 4,500 patients across 10 clinical studies, is evaluating KEYTRUDA across all settings and stages of the disease.

Additional Data and Safety Information from EORTC1325/KEYNOTE-054 (Abstract #10526)

EORTC 1325/KEYNOTE-054 is a randomized, double-blind, Phase 3 study (ClinicalTrials.gov, NCT02362594) sponsored by Merck and conducted in collaboration with the EORTC. The study is evaluating adjuvant therapy with KEYTRUDA compared to placebo in patients with resected high-risk melanoma (stage IIIA [> 1 mm lymph node metastasis], IIIB and IIIC). In total, the study enrolled 1,019 patients who were randomly assigned to receive either an intravenous infusion of KEYTRUDA 200 mg (n=514) or placebo (n=505) every three weeks for up to 1 year (a total of 18 doses). Upon documented recurrence, patients were eligible for cross-over/re-challenge with KEYTRUDA. Co-primary endpoints were RFS for all patients and RFS in patients whose tumors express PD-L1; secondary endpoints include distant metastases-free survival and overall survival (OS) in all patients and in patients whose tumors express PD-L1. RFS was defined as the time from randomization until the date of first recurrence (local, regional or distant metastasis) or death from any cause. In accordance with the trial protocol, the study is continuing in order to evaluate secondary endpoints including OS.

With an overall median follow-up of 15.1 months, in the overall intent-to-treat population the 12-month RFS rate was 75.4 percent (95% CI, 71.3-78.9) in the KEYTRUDA group and 61.0 percent (95% CI, 56.5-65.1) in the placebo group. RFS was significantly prolonged, resulting in reduced risk of recurrence or death of 43 percent with KEYTRUDA (HR=0.57; 98.4% CI, 0.43-0.74; p<0.0001) compared to placebo. At 18 months, the RFS rates were 71.4 percent (95% CI, 66.8-75.4) and 53.2 percent (95% CI, 47.9-58.2), respectively.

In patients with PD-L1 positive tumors (n=853), the 12-month RFS rate was 77.1 percent (95% CI, 72.7-80.9) in the KEYTRUDA group and 62.6 percent (95% CI, 57.7-67.0) in the placebo group. In these patients, RFS was significantly longer, resulting in reduced risk of recurrence or death of 46 percent with KEYTRUDA (HR=0.54; 95% CI, 0.42-0.69; p<0.0001) compared to placebo. RFS benefit demonstrated with KEYTRUDA was consistent in patients with PD-L1-negative tumors and in those with an undetermined tumor PD-L1 expression.

In addition, RFS benefit seen with KEYTRUDA was similar across other subgroups including stage of disease and nodal involvement; BRAF-status, sex and baseline body mass index did not significantly influence the treatment difference.

The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with advanced melanoma. Drug-related grade 3 to 5 adverse events were reported in 14.7 percent of patients in the KEYTRUDA group and 3.4 percent in patients in the placebo group. The most common treatment-related adverse events (TRAEs) for KEYTRUDA were fatigue or asthenia (37.1%), skin reactions (28.3%), diarrhea (19.1%), arthralgia (12.0%), and nausea (11.4%). The highest incidence of immune-related adverse events (irAEs), mostly grade 1 to 2, were endocrine disorders (most commonly hypothyroidism [14.3%], hyperthyroidism [10.2%], and thyroiditis [3.1%]). The incidence of grade 3-5 irAEs was 7.1 percent and included colitis (2.0%), pneumonitis (0.8%), and hepatitis (1.4%); all others had incidences ≤ 1 percent. There was one death due to myositis in the KEYTRUDA group.

About EORTC

The European Organisation for Research and Treatment of Cancer (EORTC) unites cancer clinical research experts to define better treatments for cancer patients to prolong survival and improve quality of life. Both international and multidisciplinary, EORTC’s Network comprises over 4600 collaborators involved in cancer treatment and research in more than 800 hospitals across 35 countries. Through translational and clinical research, EORTC offers an integrated approach to therapeutic strategies, drug evaluation programs, survivorship issues, and quality of life. EORTC Headquarters, a unique international clinical research infrastructure, is based in Brussels, Belgium, from where its various activities are coordinated and run.

About Melanoma

Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The incidence of melanoma has been increasing over the past four decades – approximately 232,000 new cases were diagnosed worldwide in 2012. In the U.S., melanoma is one of the most common types of cancer diagnosed and is responsible for the vast majority of skin cancer deaths. In 2018, an estimated 91,270 people are expected to be diagnosed and an estimated 9,320 people are expected to die of the disease in the U.S. alone.

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About KEYTRUDA® (pembrolizumab) Injection 100mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program, which currently involves more than 700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

KEYTRUDA® (pembrolizumab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, as a single agent, is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for pemetrexed and carboplatin.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In adults with cHL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

  • solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
  • colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In children with MSI-H cancer, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The recommended dose of KEYTRUDA is 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on TwitterFacebookInstagram, YouTube and LinkedIn.

SOURCE: Merck

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