cal activity of mogamulizumab-kpkcwas noted; there were no apparent mogamulizumab-kpkc -related external, visceral, or skeletalabnormalities.
8.2 Lactation
Risk Summary
There is no information regarding the presence of POTELIGEO in human milk, the effects onthe breastfed child, or the effects on milk production. The developmental and health benefits ofbreastfeeding should be considered along with the mother’s clinical need for POTELIGEO andany potential adverse effects on the breastfed child from POTELIGEO or from the underlyingmaternal condition.
8.3 Females and Males of Reproductive Potential
POTELIGEO is not recommended during pregnancy or in women of childbearing potential notusing contraception.Pregnancy Testing
For females of reproductive potential, verify pregnancy status prior to initiating POTELIGEO.
ContraceptionAdvise females of reproductive potential to use effective contraception during treatment withPOTELIGEO and for at least 3 months following the last dose of POTELIGEO.
8.4 Pediatric use
The safety and effectiveness of POTELIGEO in pediatric patients have not been established.
8.5 Geriatric use
Of 319 patients with MF or SS who received POTELIGEO in Trial 1, 162 (51%) were≥65years. No overall differences in effectiveness were observed between these patients and youngerpatients.
In patients aged ≥65, Grade 3 or higher adverse reactions were reported in 45% andserious adverse reactions in 36%, whereas in patients aged <65, Grade 3 or higher adversereactions were reported in 36% and serious adverse reactions in 29%.
11 DESCRIPTION
Mogamulizumab-kpkc is a recombinant humanized monoclonal antibody that targets CCchemokine receptor 4 (CCR4)-expressing cells. Mogamulizumab-kpkc is an IgG1 kappa
immunoglobulin that has a calculated molecular mass of approximately 149 kDa.
Mogamulizumab-kpkc is produced by recombinant DNA technology in Chinese hamster ovarycells.
POTELIGEO (mogamulizumab-kpkc) injection is a sterile, ready-to-use, preservative-free, clearto slightly opalescent colorless solution in a single-dose vial for dilution prior to intravenousinfusion. Each vial contains 20 mg of mogamulizumab-kpkc in 5 mL of solution. Each mL ofsolution contains 4 mg of mogamulizumab-kpkc and is formulated in: citric acid monohydrate(0.44 mg), glycine (22.5 mg), polysorbate 80 (0.2 mg), and Water for Injection, USP. Maycontain hydrochloric acid/sodium hydroxide to adjust pH to 5.5.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Mogamulizumab-kpkc is a defucosylated, humanized IgG1 kappa monoclonal antibody thatbinds to CCR4, a G protein-coupled receptor for CC chemokines that is involved in thetrafficking of lymphocytes to various organs. Non-clinical in vitro studies demonstratemogamulizumab-kpkc binding targets a cell for antibody-dependent cellular cytotoxicity(ADCC) resulting in depletion of the target cells.
CCR4 is expressed on the surface of some Tcellmalignancies and is expressed on regulatory T-cells (Treg) and a subset of Th2 T-cells.
12.2 Pharmacodynamics
Mogamulizumab-kpkc exposure-response relationships and the time course ofpharmacodynamics response are unknown.
12.3 Pharmacokinetics
Mogamulizumab-kpkc pharmacokinetics (PK) was eva luated in patients with T-cellmalignancies. Parameters are presented as the geometric mean [% coefficient of variation
(%CV)] unless otherwise specified. Mogamulizumab-kpkc concen |
