Date: 2016-12-15
Type of information: Positive opinion for the granting of a Market Authorisation in the EU
Product name: Keytruda®
Compound: pembrolizumab
Therapeutic area: Cancer - Oncology
Action mechanism:
- monoclonal antibody/immune checkpoint inhibitor/immunotherapy product. Keytruda® (pembrolizumab - MK-3475) is an investigational, highly selective monoclonal anti-PD-1 antibody designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system. MK-3475 is currently being studied in three clinical trials for advanced melanoma including a Phase III trial of MK-3475 versus ipilimumab in ipilimumab-naïve advanced melanoma patients (PN 006). Enrollment is complete in the advanced melanoma cohorts in the company’s Phase IB trial (PN 001) and the Phase II trial (PN 002) comparing two doses of MK-3475 versus chemotherapy in patients with advanced melanoma who have progressed after prior therapy. Pembrolizumab is being evaluated across more than 30 types of cancers, as monotherapy and in combination. It is anticipated that by the end of 2014, the pembrolizumab development program will grow to more than 24 clinical trials, enrolling an estimated 6,000 patients at nearly 300 clinical trial sites worldwide.
In April 2013, MK-3475 has received a Breakthrough Therapy designation for advanced melanoma from the FDA.
- Keytruda® is the first approved drug that blocks the PD-1 cellular pathway.
Company: Merck&Co (USA - NJ)
Disease: patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test
Latest news:
- • On December 19, 2016 , Merck&Co announced that Merck&Co (pembrolizumab) has been approved in Japan for the treatment of certain patients with PD-L1-positive unresectable advanced/recurrent non-small cell lung cancer (NSCLC) in the first- and second-line treatment settings at a fixed dose of 200 mg every three weeks. Merck&Co will manufacture and market Keytruda® in Japan and will promote it with Taiho Pharmaceutical. The Japanese Ministry of Health, Labour, and Welfare (MHLW) approval is supported by findings from both the KEYNOTE-024 and KEYNOTE-010 studies. The PD-L1 IHC 22C3 PharmDx™ kit made by Dako North America, Inc., an Agilent Technologies Company, was approved in Japan on Nov. 25 for use in detecting PD-L1, an immune-related biomarker expressed on some tumor cells. The diagnostic is intended to aid in identifying appropriate patients for treatment with Merck&Co including previously treated patients whose tumors have any level of PD-L1 expression and previously untreated patients whose tumors have high levels of PD-L1 expression.
- • On December 15, 2016, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of Keytruda® (pembrolizumab) 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. A final decision is expected in the first quarter of 2017. Keytruda® is currently approved in Europe for the second-line treatment of patients with locally advanced or metastatic NSCLC whose tumors express PD-L1 and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumor mutations should also have received targeted therapy before receiving Keytruda®.
- The positive opinion is based on data from KEYNOTE-024, a pivotal study which demonstrated superior overall survival and progression-free survival with Keytruda® (pembrolizumab) compared to chemotherapy in patients whose tumors expressed high levels of PD-L1 with no EGFR or ALK positive tumor mutations.
- • On October 24, 2016, the FDA approved Keytruda® (pembrolizumab) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test. The recommended dose and schedule of pembrolizumab for NSCLC is 200 mg intravenously every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
- This is the first FDA approval of a checkpoint inhibitor for first-line treatment of lung cancer. This approval also expands the indication in second-line treatment of lung cancer to include all patients with PD-L1-expressing non-small cell lung cancer. The FDA approval added the following indications for pembrolizumab:
- Patients with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] greater than or equal to 50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC.
- Patients with metastatic NSCLC whose tumors express PD-L1 (TPS greater than or equal to 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 pembrolizumab.
- Approval was based on results of two randomized, controlled trials that demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy.
In KEYNOTE-024 trial of 305 patients who had no prior treatment for metastatic NSCLC and TPS greater than or equal to 50%, those who received pembrolizumab (200 mg every 3 weeks) had a significant improvement in PFS (HR 0.50 [95% CI: 0.37, 0.68]; p<0.001) with a median PFS of 10.3 months versus 6.0 months for those receiving platinum-based chemotherapy. A pre-specified interim analysis demonstrated a statistically significant improvement in OS for patients randomized to pembrolizumab as compared with chemotherapy (HR 0.60 [95% CI: 0.41, 0.89]; p<0.005).
- In a three-arm trial of 1033 patients who were previously treated for metastatic NSCLC with a TPS greater than or equal to 1%, those randomized to pembrolizumab 2 mg/kg every 3 weeks (HR 0.71 (95% CI: 0.58, 0.88]; p<0.001) or pembrolizumab 10 mg/kg every 3 weeks (HR 0.61 [95% CI: 0.49, 0.75]; p<0.001) had an improved OS compared with patients receiving docetaxel. The median survival was 10.4 months in the pembrolizumab 2 mg/kg arm, 12.7 months in the pembrolizumab 10 mg/kg arm, and 8.5 months in the docetaxel arm.
- The most common side effects of treatment with pembrolizumab included decreased appetite, fatigue, nausea, dyspnea, cough, and constipation. Rare but serious adverse events included immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2016-10-24
UE authorization: 2017-
Favourable opinion UE: 2016-12-15
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
