European Commission Approves Merck’s KEYTRUDA® (pembrolizumab) in Combination with Chemotherapy for First-Line Treatment of Adults with Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC)

European Approval Based on KEYNOTE-407 Study Results Demonstrating Significant Improvement in Overall Survival with KEYTRUDA in Combination with Chemotherapy Compared to Chemotherapy Alone

KEYTRUDA is First Anti-PD-1 Therapy Approved in Combination with Chemotherapy in Europe for Adults with Metastatic Squamous NSCLC Regardless of PD-L1 Expression

KENILWORTH, NJ, USA I March 14, 2019 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the European Commission has approved KEYTRUDA, the company’s anti-PD-1 therapy, in combination with carboplatin and either paclitaxel or nab-paclitaxel, for the first-line treatment of adults with metastatic squamous non-small cell lung cancer (NSCLC). This approval is based on data from the Phase 3 KEYNOTE-407 trial, which demonstrated that KEYTRUDA in combination with chemotherapy significantly improved overall survival (OS) in adults with metastatic squamous NSCLC regardless of PD-L1 tumor expression status, reducing the risk of death by 36 percent compared to chemotherapy alone (HR=0.64 [95% CI, 0.49-0.85]; p=0.0008).

“In KEYNOTE-407, first-line treatment with KEYTRUDA in combination with chemotherapy resulted in significant improvements in overall survival for patients with metastatic squamous non-small cell lung cancer, regardless of PD-L1 expression,” said Dr. Luis Paz-Ares, chair of the medical oncology department, Hospital Universitario Doce de Octubre, Madrid, Spain. “Lung cancer is the leading cause of cancer death in Europe, so this approval marks an important milestone for the patients and families facing this difficult-to-treat type of lung cancer.”

The approval allows marketing of the KEYTRUDA combination in all 28 EU member states plus Iceland, Lichtenstein and Norway, at the approved dose of 200 mg every three weeks until disease progression or unacceptable toxicity. In NSCLC, KEYTRUDA is also approved in Europe for the:

  • First-line treatment of metastatic nonsquamous NSCLC in combination with pemetrexed and platinum chemotherapy in adults whose tumors have no EGFR or ALK positive mutations (KEYNOTE-189);
  • First-line treatment of metastatic squamous or nonsquamous NSCLC as monotherapy in adults whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%) with no EGFR or ALK positive tumor mutations (KEYNOTE-024); and
  • Treatment of locally advanced or metastatic NSCLC in adults whose tumors express PD-L1 (TPS ≥1%) and who have received at least one prior chemotherapy regimen (KEYNOTE-010).

“KEYTRUDA provides a foundation for the treatment of lung cancer in Europe, and this approval expands our first-line combination indications to include adults with metastatic squamous non-small cell lung cancer,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “This is a meaningful treatment advance as an anti-PD-1 combination therapy is now approved in Europe for this type of non-small cell lung cancer. With this approval, more patients with non-small cell lung cancer may have the opportunity to benefit from combination therapy with KEYTRUDA.”

Data Supporting the European Approval

The approval was based on data from KEYNOTE-407, a Phase 3, randomized, double-blind, multicenter, placebo-controlled study evaluating KEYTRUDA in combination with carboplatin-paclitaxel or nab-paclitaxel compared with carboplatin-paclitaxel or nab-paclitaxel alone. The dual primary endpoints are OS and progression-free survival (PFS); secondary endpoints include objective response rate (ORR) and duration of response (DOR). The study enrolled 559 patients who were randomized (1:1) to receive one of the following treatments via intravenous infusion:

  • KEYTRUDA 200 mg and carboplatin AUC 6 mg/mL/min on Day 1 of each 21-day cycle for four cycles and paclitaxel 200 mg/m2 on Day 1 of each 21-day cycle for four cycles or nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 of each 21-day cycle for four cycles, followed by KEYTRUDA 200 mg every three weeks. KEYTRUDA was administered prior to chemotherapy on Day 1.
  • Placebo and carboplatin AUC 6 mg/mL/min on Day 1 of each 21-day cycle for four cycles and paclitaxel 200 mg/m2 on Day 1 of each 21-day cycle for four cycles or nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 of each 21-day cycle for four cycles, followed by placebo every 3 weeks.

In KEYNOTE-407, KEYTRUDA in combination with carboplatin and either paclitaxel or nab-paclitaxel significantly improved OS, reducing the risk of death by 36 percent compared to chemotherapy alone (HR=0.64 [95% CI, 0.49-0.85]; p<0.0008). The KEYTRUDA combination also demonstrated improved PFS, with a reduction in the risk of progression or death of 44 percent compared to chemotherapy alone (HR=0.56 [95% CI, 0.45-0.70]; p<0.0001). Among patients who received the KEYTRUDA combination, the ORR was 58 percent (95% CI, 52-64) compared to 38 percent (95% CI, 33-44) for patients who received chemotherapy alone (p<0.0001). The median DOR was 7.7 months (range, 1.1+ to 14.7+ months) for patients who received the KEYTRUDA combination compared to 4.8 months (range, 1.3+ to 15.8+ months) for patients who received chemotherapy alone.

The safety of KEYTRUDA in combination with chemotherapy has been evaluated in 791 patients with NSCLC receiving 200 mg, 2 mg/kg or 10 mg/kg KEYTRUDA every three weeks, in clinical studies. In this patient population, the most frequent adverse reactions were nausea (49%), anemia (48%), fatigue (38%), constipation (34%), diarrhea (31%), neutropenia (29%), and decreased appetite (28%). Incidences of Grade 3-5 adverse reactions were 67 percent for the KEYTRUDA combination and 66 percent for chemotherapy alone.

About Lung Cancer in Europe (NSCLC)

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death in Europe and worldwide. In 2018, there were nearly 388,000 deaths from lung cancer in Europe. The two main types of lung cancer are non-small cell and small cell. NSCLC is the most common type of lung cancer, accounting for about 85 percent of all cases. There are several subtypes of NSCLC, including adenocarcinoma (accounting for 40% of lung cancers), squamous cell carcinoma (25 to 30%) and large cell carcinoma (10 to 15%).

About KEYTRUDA® (pembrolizumab) Injection

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. There are currently more than 900 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 in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma. The recommended dose of KEYTRUDA in patients with unresectable or metastatic melanoma is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with melanoma is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence.

Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic 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 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.

In metastatic NSCLC, the recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes 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 the chemotherapy agents administered in combination with KEYTRUDA, as appropriate.

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 as an intravenous infusion over 30 minutes 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 3 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 as an intravenous infusion over 30 minutes 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 as an intravenous infusion over 30 minutes 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.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 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 confirmatory trials. KEYTRUDA is not recommended for the treatment of patients with PMBCL who require urgent cytoreductive therapy.

In adults with PMBCL, KEYTRUDA is administered as an intravenous infusion over 30 minutes of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with PMBCL, KEYTRUDA is administered as an intravenous infusion over 30 minutes 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 (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) ≥10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. 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 indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) 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 as an intravenous infusion over 30 minutes 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 as an intravenous infusion over 30 minutes 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 as an intravenous infusion over 30 minutes 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 (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 an intravenous infusion over 30 minutes of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. 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 an intravenous infusion over 30 minutes of 200 mg every three weeks until disease progression, unacceptable toxicity or up to 24 months in patients without disease progression.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. 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 an intravenous infusion over 30 minutes of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma. 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 in adults is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. The recommended dose of KEYTRUDA in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every three weeks until disease progression or 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, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology 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 Twitter, Facebook, Instagram, YouTube and LinkedIn.

SOURCE: Merck

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