Approval Based on Data Showing Improved Overall Survival and Progression-Free Survival with KEYTRUDA Compared to Chemotherapy
First Anti-PD-1 Therapy Approved in Europe for Previously Untreated Patients with Metastatic NSCLC
KENILWORTH, NJ, USA I January 31, 2017 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the European Commission has approved KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) in adults whose tumors have high PD-L1 expression (tumor proportion score [TPS] of 50 percent or more) with no EGFR or ALK positive tumor mutations.
“The approval of KEYTRUDA as a first treatment instead of chemotherapy for patients who express high levels of PD-L1 has the potential to transform the way metastatic non-small cell lung cancer is treated,” said Dr. Roy Baynes, senior vice president, head of clinical development, and chief medical officer, Merck Research Laboratories. “We are committed to ensuring that patients in Europe – who are in need of new treatment options – are able to quickly gain access to KEYTRUDA.”
The approval is based on phase 3 data which demonstrated superior overall survival (OS) and progression-free survival (PFS) with KEYTRUDA compared to chemotherapy, the current standard of care for advanced NSCLC. The approval allows marketing of KEYTRUDA 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 August 2016, KEYTRUDA (pembrolizumab) (2 mg/kg every three weeks) was approved in Europe for previously-treated patients with locally advanced or metastatic NSCLC whose tumors express PD-L1 (TPS of 1 percent or more) and who have received at least one prior chemotherapy regimen.
“The data demonstrate that KEYTRUDA provided meaningful improvements in survival versus the current standard of care in patients whose tumors express high levels of PD-L1,” said Dr. Luis Paz-Ares, chair of the medical oncology department, Hospital Universitario Doce de Octubre, Madrid, Spain. “These findings supporting the approval also provide further rationale for biomarker testing in order to identify those patients more likely to benefit the most from treatment with KEYTRUDA.”
About KEYNOTE-024
The European Commission’s approval is based on data from KEYNOTE-024, a randomized, open-label, phase 3 study evaluating KEYTRUDA monotherapy at a fixed dose of 200 mg compared to standard of care platinum-containing chemotherapy (pemetrexed+carboplatin, pemetrexed+cisplatin, gemcitabine+cisplatin, gemcitabine+carboplatin, or paclitaxel+carboplatin) for the treatment of patients with both squamous and non-squamous metastatic NSCLC. The study enrolled 305 patients who had not received prior systemic chemotherapy treatment for their metastatic disease and whose tumors had high PD-L1 expression with no EGFR or ALK aberrations. The primary endpoint was PFS; additional efficacy outcome measures were OS and objective response rate (ORR).
In the study, KEYTRUDA reduced the risk of disease progression or death by 50 percent compared to chemotherapy (HR, 0.50 [95% CI, 0.37, 0.68]; p<0.001). The median PFS for KEYTRUDA was 10.3 months (95% CI, 6.7-not reached) compared to 6.0 months for chemotherapy (95% CI, 4.2-6.2). At six months and 12 months, respectively, 62 percent and 48 percent of patients treated with KEYTRUDA were alive and had no disease progression compared to 50 percent and 15 percent of those receiving chemotherapy.
Additionally, KEYTRUDA resulted in a 40 percent reduction in the risk of death compared to chemotherapy (HR, 0.60 [95% CI, 0.41, 0.89]; p=0.005); this finding includes the 66 patients (43.7%) on the chemotherapy arm who crossed over in-study to receive KEYTRUDA once their cancer had progressed; median OS was not reached in either group. The OS rate at six months and 12 months, respectively, was 80 percent and 70 percent in patients treated with KEYTRUDA compared to 72 percent and 54 percent in those receiving chemotherapy.
Further, ORR was 45 percent for patients receiving KEYTRUDA (pembrolizumab) (95% CI, 37-53), including six complete responses, compared to 28 percent with chemotherapy (95% CI, 21-36), including one complete response.
The safety analysis supporting the European approval of KEYTRUDA was based on 2,953 patients with advanced melanoma or NSCLC across four doses (2 mg/kg every three weeks, 200 mg every three weeks, or 10 mg/kg every two or three weeks) in studies KEYNOTE-001, KEYNOTE-002, KEYNOTE-010 and KEYNOTE-024 combined. The most common adverse reactions (≥10%) with KEYTRUDA were fatigue (24%), rash (19%), pruritus (17%), diarrhea (12%), nausea (11%) and arthralgia (10%). The majority of adverse reactions reported were of Grade 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions.
About KEYTRUDA® (pembrolizumab)
KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA 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.
KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.
KEYTRUDA Indications and Dosing in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA 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 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 (pembrolizumab).
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.
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.
About Merck
For over a century, Merck has been a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. 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. For more information, visit www.merck.com and connect with us on Twitter, Facebook, YouTube and LinkedIn.
SOURCE: Merck
Post Views: 14
Approval Based on Data Showing Improved Overall Survival and Progression-Free Survival with KEYTRUDA Compared to Chemotherapy
First Anti-PD-1 Therapy Approved in Europe for Previously Untreated Patients with Metastatic NSCLC
KENILWORTH, NJ, USA I January 31, 2017 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the European Commission has approved KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) in adults whose tumors have high PD-L1 expression (tumor proportion score [TPS] of 50 percent or more) with no EGFR or ALK positive tumor mutations.
“The approval of KEYTRUDA as a first treatment instead of chemotherapy for patients who express high levels of PD-L1 has the potential to transform the way metastatic non-small cell lung cancer is treated,” said Dr. Roy Baynes, senior vice president, head of clinical development, and chief medical officer, Merck Research Laboratories. “We are committed to ensuring that patients in Europe – who are in need of new treatment options – are able to quickly gain access to KEYTRUDA.”
The approval is based on phase 3 data which demonstrated superior overall survival (OS) and progression-free survival (PFS) with KEYTRUDA compared to chemotherapy, the current standard of care for advanced NSCLC. The approval allows marketing of KEYTRUDA 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 August 2016, KEYTRUDA (pembrolizumab) (2 mg/kg every three weeks) was approved in Europe for previously-treated patients with locally advanced or metastatic NSCLC whose tumors express PD-L1 (TPS of 1 percent or more) and who have received at least one prior chemotherapy regimen.
“The data demonstrate that KEYTRUDA provided meaningful improvements in survival versus the current standard of care in patients whose tumors express high levels of PD-L1,” said Dr. Luis Paz-Ares, chair of the medical oncology department, Hospital Universitario Doce de Octubre, Madrid, Spain. “These findings supporting the approval also provide further rationale for biomarker testing in order to identify those patients more likely to benefit the most from treatment with KEYTRUDA.”
About KEYNOTE-024
The European Commission’s approval is based on data from KEYNOTE-024, a randomized, open-label, phase 3 study evaluating KEYTRUDA monotherapy at a fixed dose of 200 mg compared to standard of care platinum-containing chemotherapy (pemetrexed+carboplatin, pemetrexed+cisplatin, gemcitabine+cisplatin, gemcitabine+carboplatin, or paclitaxel+carboplatin) for the treatment of patients with both squamous and non-squamous metastatic NSCLC. The study enrolled 305 patients who had not received prior systemic chemotherapy treatment for their metastatic disease and whose tumors had high PD-L1 expression with no EGFR or ALK aberrations. The primary endpoint was PFS; additional efficacy outcome measures were OS and objective response rate (ORR).
In the study, KEYTRUDA reduced the risk of disease progression or death by 50 percent compared to chemotherapy (HR, 0.50 [95% CI, 0.37, 0.68]; p<0.001). The median PFS for KEYTRUDA was 10.3 months (95% CI, 6.7-not reached) compared to 6.0 months for chemotherapy (95% CI, 4.2-6.2). At six months and 12 months, respectively, 62 percent and 48 percent of patients treated with KEYTRUDA were alive and had no disease progression compared to 50 percent and 15 percent of those receiving chemotherapy.
Additionally, KEYTRUDA resulted in a 40 percent reduction in the risk of death compared to chemotherapy (HR, 0.60 [95% CI, 0.41, 0.89]; p=0.005); this finding includes the 66 patients (43.7%) on the chemotherapy arm who crossed over in-study to receive KEYTRUDA once their cancer had progressed; median OS was not reached in either group. The OS rate at six months and 12 months, respectively, was 80 percent and 70 percent in patients treated with KEYTRUDA compared to 72 percent and 54 percent in those receiving chemotherapy.
Further, ORR was 45 percent for patients receiving KEYTRUDA (pembrolizumab) (95% CI, 37-53), including six complete responses, compared to 28 percent with chemotherapy (95% CI, 21-36), including one complete response.
The safety analysis supporting the European approval of KEYTRUDA was based on 2,953 patients with advanced melanoma or NSCLC across four doses (2 mg/kg every three weeks, 200 mg every three weeks, or 10 mg/kg every two or three weeks) in studies KEYNOTE-001, KEYNOTE-002, KEYNOTE-010 and KEYNOTE-024 combined. The most common adverse reactions (≥10%) with KEYTRUDA were fatigue (24%), rash (19%), pruritus (17%), diarrhea (12%), nausea (11%) and arthralgia (10%). The majority of adverse reactions reported were of Grade 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions.
About KEYTRUDA® (pembrolizumab)
KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA 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.
KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.
KEYTRUDA Indications and Dosing in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA 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 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 (pembrolizumab).
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.
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.
About Merck
For over a century, Merck has been a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. 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. For more information, visit www.merck.com and connect with us on Twitter, Facebook, YouTube and LinkedIn.
SOURCE: Merck
Post Views: 14
