Product InformationRegistration Status: Active
KEYTRUDA SOLUTION FOR INFUSION 25MG/ML is approved to be sold in Singapore with effective from 2015-10-27. It is marketed by MSD PHARMA (SINGAPORE) PTE LTD, with the registration number of SIN14881P.
This product contains Pembrolizumab 25mg/mL in the form of INFUSION, SOLUTION CONCENTRATE. It is approved for INTRAVENOUS use.
This product is manufactured by MSD International GmbH T/A MSD Ireland (Carlow) in IRELAND.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Pembrolizumab is a highly selective IgG4-kappa humanized monoclonal antibody against PD-1 receptor. It was generated by grafting the variable sequences of a very high-affinity mouse antihuman PD-1 antibody onto a human IgG4-kappa isotype with the containing a stabilizing S228P Fc mutation.[A18829] It contains 32 cysteine residues and the complete folded molecule includes 4 disulfide linkages as interchain bonds and 23 interchain bonds.[F136] It was developed by Merck & Co and firstly approved for the treatment of metastatic malignant melanoma. This is the first approved therapy against PD-1.[A7624] It was approved firstly by the FDA on September 4, 2014.[L2954] Its approval in melanoma was extended to several countries such as Australia, Israel, Korea, Macau, the European Union and the United Arab Emirates.[A33350] On June 12, 2018, Pembrolizumab was approved for the treatment of cervical cancer under the status of accelerated approval.[L2955]
Pembrolizumab is indicated for the treatment of: -Patients with unresectable or metastatic melanoma.[FDA label] -As a single therapy, pembrolizumab is indicated for first-line treatment of patients with metastatic non-small cell lung cancer 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.[F137] -As a single therapy, pembrolizumab is indicated for first-line treatment of patients with metastatic non-small cell lung cancer 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 treatment.[F137] The following indications present the status of accelerated approval based on tumor response rate and durability of the response and thus, the approval of this indications are contingent upon verification and description of clinical benefit in confirmatory trials. -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.[L2955] -In combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer.[F137] -Patients with recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy.[F137] -Treatment of adults and pediatric patients with refractory classical Hodgkin lymphoma or who have relapsed after 3 or more prior lines of therapy.[F137] -Treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma or who have relapsed after 2 or more prior lines of therapy.[F137] -Treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.[F137] -Patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy.[F137] -Treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high or mismatch repair deficient with solid tumors that have progressed following previous treatment and colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.[F137] -Patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction 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.[F137]
Mechanism of Action
Pembrolizumab, as an IgG4 subclass antibody, is preferred over other subclasses as it only induces weakly the complement and cell activation due to low affinity to C1q and Fc receptors. It binds with high affinity to the cell surface receptor programmed cell death protein 1 (PD-1) and it antagonizes its interaction with its known ligands PD-L1 and PD-L2. In normal circumstances, the binding of the ligands of PD-1 to the receptor inhibits the TCR-mediated T cell proliferation and cytokine production. This inhibitory signal seems to be essential for self-tolerance, collateral damage minimizing after immune response against a pathogen and maternal tolerance to fetal tissue. Therefore, the binding of pembrolizumab to PD-1 prevents the inhibitory pathway causing a physiological shift to immune reactivity and enhancing tumor immunosurveillance and anti-tumor immune response.[A18829]
- When administered intravenously, pembrolizumab is completely bioavailable. When administered in repeated doses every 3 weeks, the systemic accumulation accounts for a 2.2 fold increase.[A18829] the reported time to reach steady-state is of 18 weeks.[F136] The absorption profile of pembrolizumab is proportionally increased with increases in the dosage.[A33365]
- The volume of distribution at steady state of pembrolizumab is 7.5 L which indicated a limited extravascular distribution.[F136]
- Pembrolizumab is catalyzed into small peptides and single amino acids via general protein degradation but it does not rely on metabolism for clearance.[A18829]
Clearance is increased proportionally with the body weight and the mean clearance is registered to be 0.22 L/day. The renal clearance of pembrolizumab is not clinically modified in a significant manner by the presence of mild to moderate renal impairment.[A18829]
Pembrolizumab seems to be very well tolerated for a cancer therapy and the rate of discontinuations is reported to be of 14%. The presence of side effects of grade 3-4 is 10-14%. Due to the mechanism of action, the immune response was highly managed with treatment interruption and corticosteroid treatment.[A18829] even though fertility studies have not been performed, there are no notable effects in reproductive organs in not sexually mature animals.[FDA label]
Lambrolizumab | Pembrolizumab |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.