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Mogamulizumab-kpkc Injection





Mogamulizumab-kpkc is a recombinant humanized monoclonal antibody that targets CC chemokine 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 ovary cells.

Mogamulizumab-kpkc injection is a sterile, ready-to-use, preservative-free, clear to slightly opalescent colorless solution in a single-dose vial for dilution prior to intravenous infusion. Each vial contains 20 mg of mogamulizumab-kpkc in 5 mL of solution. Each mL of solution 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. May contain hydrochloric acid/sodium hydroxide to adjust pH to 5.5.


Mogamulizumab-kpkc is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy.


3.1 Recommended Dosage

The recommended dose of mogamulizumab-kpkc is 1 mg/kg administered as an intravenous infusion over at least 60 minutes. Administer on days 1, 8, 15, and 22 of the first 28-day cycle, then on days 1 and 15 of each subsequent 28-day cycle until disease progression or unacceptable toxicity.

Administer mogamulizumab-kpkc within 2 days of the scheduled dose. If a dose is missed, administer the next dose as soon as possible and resume dosing schedule.

Do not administer mogamulizumab-kpkc subcutaneously or by rapid intravenous administration.

Recommended Premedications

Administer premedication with diphenhydramine and acetaminophen for the first mogamulizumab-kpkc infusion.

3.2 Dose Modifications for Toxicity

Dermatologic Toxicity

 Permanently discontinue mogamulizumab-kpkc for life-threatening (Grade 4) rash or for any Stevens- Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) [see Warnings and Precautions (5.1)]. If SJS or TEN is suspected, stop mogamulizumab-kpkc and do not resume unless SJS or TEN has been excluded and the cutaneous reaction has resolved to Grade 1 or less.

 If moderate or severe (Grades 2 or 3) rash occurs, interrupt mogamulizumab-kpkc and administer at least 2 weeks of topical corticosteroids. If rash improves to Grade 1 or less, mogamulizumab-kpkc may be resumed [see Warnings and Precautions (5.1)].

 If mild (Grade 1) rash occurs, consider topical corticosteroids.

Infusion Reactions

 Permanently discontinue mogamulizumab-kpkc for a life-threatening (Grade 4) infusion reaction [see Warnings and Precautions (5.2)].

 Temporarily interrupt the infusion of mogamulizumab-kpkc for mild to severe (Grades 1 to 3) infusion reactions and treat symptoms. Reduce the infusion rate by at least 50% when restarting the infusion after symptoms resolve. If reaction recurs and is unmanageable, discontinue infusion. [see Warnings and Precautions (5.2)].

 If an infusion reaction occurs, administer premedication (such as diphenhydramine and acetaminophen) for subsequent mogamulizumab-kpkc infusions.

3.3 Preparation and Administration


 Visually inspect drug product solution for particulate matter and discoloration prior to administration. Mogamulizumab-kpkc is a clear to slightly opalescent colorless solution. Discard the vial if cloudiness, discoloration, or particulates are observed.

 Calculate the dose (mg/kg) and number of vials of mogamulizumab-kpkc needed to prepare the infusion solution based on patient weight.

 Aseptically withdraw the required volume of mogamulizumab-kpkc into the syringe and transfer into an intravenous (IV) bag containing 0.9% Sodium Chloride Injection, USP. The final concentration of the diluted solution should be between 0.1 mg/mL to 3.0 mg/mL.

 Mix diluted solution by gentle inversion. Do not shake.

 Discard any unused portion left in the vial.

The diluted solution is compatible with polyvinyl chloride (PVC) or polyolefin (PO) infusion bags.


 Administer infusion solution over at least 60 minutes through an intravenous line containing a sterile, low protein binding, 0.22 micron (or equivalent) in-line filter.

 Do not mix mogamulizumab-kpkc with other drugs.

 Do not co-administer other drugs through the same intravenous line.

Storage of Diluted Solution

After preparation, infuse the mogamulizumab-kpkc solution immediately, or store under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 4 hours from the time of infusion preparation. Do not freeze. Do not shake.




5.1 Dermatologic Toxicity

Fatal and life-threatening skin adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have occurred in recipients of mogamulizumab-kpkc. Rash (drug eruption) is one of the most common adverse reactions associated with mogamulizumab-kpkc. In Trial 1, 25% (80/319) of patients treated with mogamulizumab-kpkc had an adverse reaction of drug eruption, with 18% of these cases being severe (Grade 3) and 82% of these cases being Grade 1 or 2. Of 528 patients treated with mogamulizumab-kpkc in clinical trials, Grade 3 skin adverse reactions were reported in 3.6%, Grade 4 skin adverse reactions in <1%, and SJS in <1%.

The onset of drug eruption is variable, and the affected areas and appearance vary. In Trial 1, the median time to onset was 15 weeks, with 25% of cases occurring after 31 weeks. The more common presentations reported included papular or maculopapular rash, lichenoid, spongiotic or granulomatous dermatitis, and morbilliform rash. Other presentations included scaly plaques, pustular eruption, folliculitis, non-specific dermatitis, and psoriasiform dermatitis.

Monitor patients for rash throughout the treatment course. Management of dermatologic toxicity includes topical corticosteroids and interruption or permanent cessation of mogamulizumab-kpkc [see Dosage and Administration (3.2)]. Consider skin biopsy to help distinguish drug eruption from disease progression.

Discontinue mogamulizumab-kpkc permanently for SJS or TEN or for any life-threatening (Grade 4) reaction. For possible SJS or TEN, interrupt mogamulizumab-kpkc and do not restart unless SJS or TEN is ruled out and the cutaneous reaction has resolved to Grade 1 or less.

5.2 Infusion Reactions

Fatal and life-threatening infusion reactions have been reported in patients treated with mogamulizumab-kpkc. In Trial 1, infusion reactions occurred in 35% (112/319) of patients treated with mogamulizumab-kpkc, with 8% of these reactions being severe (Grade 3). Most reactions (approximately 90%) occur during or shortly after the first infusion. Infusion reactions can also occur with subsequent infusions. The most commonly reported signs include chills, nausea, fever, tachycardia, rigors, headache, and vomiting.

Consider premedication (such as diphenhydramine and acetaminophen) for the first infusion of mogamulizumab-kpkc in all patients. Whether premedication reduces the risk or severity of these reactions is not established. In Trial 1, infusion reactions occurred in 42% of patients without premedication and 32% of patients with premedication. Monitor patients closely for signs and symptoms of infusion reactions and interrupt the infusion for any grade reaction and treat promptly [see Dosage and Administration (3.2)].

5.3 Infections

Fatal and life-threatening infections have occurred in patients treated with mogamulizumab-kpkc, including sepsis, pneumonia, and skin infection. In Trial 1, 18% (34/184) of patients randomized to mogamulizumab-kpkc had Grade 3 or higher infection or an infection-related serious adverse reaction. Monitor patients for signs and symptoms of infection and treat promptly.

5.4 Autoimmune Complications

Fatal and life-threatening immune-mediated complications have been reported in recipients of mogamulizumab-kpkc. Grade 3 or higher immune-mediated or possibly immune-mediated reactions have included myositis, myocarditis, polymyositis, hepatitis, pneumonitis, and a variant of Guillain- Barré syndrome. Use of systemic immunosuppressants for immune-mediated reactions was reported in 1.9% (6/319) of recipients of mogamulizumab-kpkc in Trial 1, including for a case of Grade 2 polymyalgia rheumatica. New-onset hypothyroidism (Grade 1 or 2) was reported in 1.3% of patients and managed with observation or levothyroxine. Interrupt or permanently discontinue mogamulizumab-kpkc as appropriate for suspected immune-mediated adverse reactions. Consider the benefit/risk of mogamulizumab-kpkc in patients with a history of autoimmune disease.

5.5 Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) after Mogamulizumab-kpkc

Increased risks of transplant complications have been reported in patients who receive allogeneic HSCT after mogamulizumab-kpkc including severe (Grade 3 or 4) acute graft-versus-host disease (GVHD), steroid-refractory GVHD, and transplant-related death. Among recipients of pre-transplantation mogamulizumab-kpkc, a higher risk of transplant complications has been reported if mogamulizumab-kpkc is given within a shorter time frame (approximately 50 days) before HSCT. Follow patients closely for early evidence of transplant-related complications.


The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

 Dermatologic Toxicity [see Warnings and Precautions (5.1)].

 Infusion Reactions [see Warnings and Precautions (5.2)].

 Infections [see Warnings and Precautions (5.3)].

 Autoimmune Complications [see Warnings and Precautions (5.4)].

 Complications of Allogeneic HSCT after mogamulizumab-kpkc [see Warnings and Precautions (5.5)].

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Trial 1

The data described below reflect exposure to mogamulizumab-kpkc in a randomized, open-label, actively controlled clinical trial for adult patients with MF or SS who received at least one prior systemic therapy [see Clinical Studies]. Of 370 patients treated, 184 (57% with MF, 43% with SS) received mogamulizumab-kpkc as randomized treatment and 186 (53% with MF, 47% with SS) received vorinostat. In the vorinostat arm, 135 patients (73%) subsequently crossed over to mogamulizumab-kpkc for a total of 319 patients treated with mogamulizumab-kpkc.

Mogamulizumab-kpkc was administered at 1 mg/kg intravenously over at least 60 minutes on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of subsequent 28-day cycles. Premedication (diphenhydramine, acetaminophen) was optional and administered to 65% of randomized patients for the first infusion. The comparator group received vorinostat 400 mg orally once daily, given continuously in 28-day cycles. Treatment continued until unacceptable toxicity or progressive disease.

The median age was 64 years (range, 25 to 101 years), 58% of patients were male, 70% were white, and 99% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients had a median of 3 prior systemic therapies. The trial required an absolute neutrophil count (ANC) ≥1500/μL (≥1000/μL if bone marrow was involved), platelet count ≥100,000/μL (≥75,000/μL if bone marrow was involved), creatinine clearance >50 mL/min or serum creatinine ≤1.5 mg/dL, and hepatic transaminases ≤2.5 times upper limit of normal (ULN) (≤5 times ULN if lymphomatous liver infiltration). Patients with active autoimmune disease, active infection, autologous HSCT within 90 days, or prior allogeneic HSCT were excluded.

During randomized treatment, the median duration of exposure to mogamulizumab-kpkc was 5.6 months, with 48% (89/184) of patients with at least 6 months of exposure and 23% (43/184) with at least 12 months of exposure. The median duration of exposure to vorinostat was 2.8 months, with 22% (41/186) of patients with at least 6 months of exposure.

Fatal adverse reactions within 90 days of the last dose occurred in 2.2% (7/319) of patients who received mogamulizumab-kpkc as randomized or crossover treatment.

Serious adverse reactions were reported in 36% (66/184) of patients randomized to mogamulizumab-kpkc and most often involved infection (16% of patients; 30/184). Serious adverse reactions reported in >2% of patients randomized to mogamulizumab-kpkc were pneumonia (5%), sepsis (4%), pyrexia (4%), and skin infection (3%); other serious adverse reactions, each reported in 2% of patients, included hepatitis, pneumonitis, rash, infusion related reaction, lower respiratory tract infection, and renal insufficiency. Mogamulizumab-kpkc was discontinued for adverse reactions in 18% of randomized patients, most often due to rash or drug eruption (7.1%).

Common Adverse Reactions

The most common adverse reactions (reported in ≥20% of patients randomized to mogamulizumab-kpkc) were rash (including drug eruption), infusion related reactions, fatigue, diarrhea, upper respiratory tract infection and musculoskeletal pain. Other common adverse reactions (reported in ≥10% of patients randomized to mogamulizumab-kpkc) included skin infection, pyrexia, nausea, edema, thrombocytopenia, headache, constipation, mucositis, anemia, cough and hypertension. Table 1 summarizes common adverse reactions having a ≥2% higher incidence with mogamulizumab-kpkc than with vorinostat in Trial 1.

Table 1: Common Adverse Reactions (≥10%) with ≥2% Higher Incidence in the Mogamulizumab-kpkc Arm

a Adverse reactions include groupings of individual preferred terms.

b Includes adverse reactions reported up to 90 days after randomized treatment.

Rash/Drug Eruption includes: dermatitis (allergic, atopic, bullous, contact, exfoliative, infected), drug eruption, palmoplantar keratoderma, rash (generalized, macular, maculopapular, papular, pruritic, pustular), skin reaction, toxic skin eruption

Upper Respiratory Tract Infection includes: laryngitis viral, nasopharyngitis, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, viral upper respiratory tract infection

Skin Infection includes: cellulitis, dermatitis infected, erysipelas, impetigo, infected skin ulcer, periorbital cellulitis, skin bacterial infection, skin infection, staphylococcal skin infection

Musculoskeletal Pain includes: back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, pain in extremity

Mucositis includes: aphthous stomatitis, mouth ulceration, mucosal inflammation, oral discomfort, oral pain, oropharyngeal pain, stomatitis

Other Common Adverse Reactions in ≥10% of Mogamulizumab-kpkc Arma, b

General disorders: fatigue (31%), edema (16%)

Gastrointestinal disorders: diarrhea (28%), nausea (16%), constipation (13%)

Blood and lymphatic system disorders: thrombocytopenia (14%), anemia (12%)

Nervous system disorders: headache (14%)

Vascular disorders: hypertension (10%)

Respiratory disorders: cough (11%)

Adverse Reactions in ≥5% but <10% of Mogamulizumab-kpkc Arma, b

Infections: candidiasis (9%), urinary tract infection (9%), folliculitis (8%), pneumonia (6%), otitis (5%), herpesvirus infection (5%)

Investigations: renal insufficiency (9%), hyperglycemia (9%), hyperuricemia (8%), weight increase (8%), weight decrease (6%), hypomagnesemia (6%)

Psychiatric disorders: insomnia (9%), depression (7%)

Skin and subcutaneous disorders: xerosis (8%), alopecia (7%)

Nervous system disorders: dizziness (8%), peripheral neuropathy (7%)

Metabolism and nutrition disorders: decreased appetite (8%)

Respiratory disorders: dyspnea (7%)

General disorders: chills (7%)

Gastrointestinal disorders: vomiting (7%), abdominal pain (5%)

Injury, poisoning and procedural complications: fall (6%)

Musculoskeletal disorders: muscle spasms (5%)

Cardiovascular disorders: arrhythmia (5%)

Eye disorders: conjunctivitis (5%)

Selected Other Adverse Reactionsa, b

 Tumor lysis syndrome (<1%)

 Myocardial ischemia or infarction (<1%)

 Cardiac failure (<1%)

a Includes grouped terms

b From 184 patients randomized to mogamulizumab-kpkc

Table 2 summarizes common treatment-emergent laboratory abnormalities having a ≥2% higher incidence with mogamulizumab-kpkc than with vorinostat.

Table 2: Common New or Worsening Laboratory Abnormalities (≥10%) with ≥2% Higher Incidence in the Mogamulizumab-kpkc Arm

a Includes laboratory abnormalities, reported up to 90 days after treatment, that are new or worsening in grade or with worsening from baseline unknown.

b Out of 99 evaluable recipients of mogamulizumab-kpkc and 36 evaluable recipients of vorinostat.

Other common treatment-emergent laboratory abnormalities in the mogamulizumab-kpkc arm included hyperglycemia (52%; 4% Grade 3-4), anemia (35%; 2% Grade 3-4), thrombocytopenia (29%, none Grade 3-4), aspartate transaminase (AST) increased (25%; 2% Grade 3-4), alanine transaminase (ALT) increased (18%; 1% Grade 3-4), alkaline phosphatase increased (17%; 0% Grade 3-4), and neutropenia (10%; 2% Grade 3-4). Grade 4 treatment-emergent laboratory abnormalities observed in ≥1% of the mogamulizumab-kpkc arm included lymphopenia (5%), leukopenia (1%), and hypophosphatemia (1%).

6.2 Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to mogamulizumab-kpkc with the incidences of antibodies in other studies or to other products may be misleading.

Among 258 patients treated with mogamulizumab-kpkc in Trial 1, 10 (3.9%) tested positive for treatment-emergent (treatment-induced or treatment-boosted) anti-mogamulizumab-kpkc antibodies by an electrochemiluminescent assay. There were no positive neutralizing antibody responses.

6.3 Postmarketing Safety Information

The following adverse reactions have been identified during post-approval use of mogamulizumab-kpkc. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Infections: Hepatitis B virus reactivation

Cardiac disorders: Stress cardiomyopathy


8.1 Pregnancy

Risk Summary

There are no available data on mogamulizumab-kpkc use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In an animal reproduction study, administration of mogamulizumab-kpkc to pregnant cynomolgus monkeys from the start of organogenesis through delivery did not show a potential for adverse developmental outcomes at maternal systemic exposures 27 times the exposure in patients at the recommended dose, based on AUC (see Data).

In general, IgG molecules are known to cross the placental barrier and in the monkey reproduction study mogamulizumab-kpkc was detected in fetal plasma. Therefore, mogamulizumab-kpkc has the potential to be transmitted from the mother to the developing fetus. Mogamulizumab-kpkc is not recommended during pregnancy or in women of childbearing potential not using contraception.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.


Animal Data

The effects of mogamulizumab-kpkc on embryo-fetal development were evaluated in 12 pregnant cynomolgus monkeys that received mogamulizumab-kpkc once weekly by intravenous administration from the start of organogenesis through delivery at an exposure level 27 times higher than the clinical dose. Mogamulizumab-kpkc administration did not show a potential for embryo-fetal lethality, teratogenicity, or fetal growth retardation and did not result in spontaneous abortion or increased fetal death. In surviving fetuses (10 of 12 compared with 11 of 12 in the control group) of cynomolgus monkeys treated with mogamulizumab-kpkc, a decrease in CCR4-expressing lymphocytes due to the pharmacological activity of mogamulizumab-kpkc was noted; there were no apparent mogamulizumab-kpkc -related external, visceral, or skeletal abnormalities.

8.2 Lactation

Risk Summary

There is no information regarding the presence of mogamulizumab-kpkc in human milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mogamulizumab-kpkc and any potential adverse effects on the breastfed child from mogamulizumab-kpkc or from the underlying maternal condition.

8.3 Females and Males of Reproductive Potential

Mogamulizumab-kpkc is not recommended during pregnancy or in women of childbearing potential not using contraception.

Pregnancy Testing

For females of reproductive potential, verify pregnancy status prior to initiating mogamulizumab-kpkc.


Advise females of reproductive potential to use effective contraception during treatment with mogamulizumab-kpkc and for at least 3 months following the last dose of mogamulizumab-kpkc.

8.4 Pediatric Use

The safety and effectiveness of mogamulizumab-kpkc in pediatric patients have not been established.

8.5 Geriatric Use

Of 319 patients with MF or SS who received mogamulizumab-kpkc in Trial 1, 162 (51%) were ≥65 years. No overall differences in effectiveness were observed between these patients and younger patients. In patients aged ≥65, Grade 3 or higher adverse reactions were reported in 45% and serious adverse reactions in 36%, whereas in patients aged <65, Grade 3 or higher adverse reactions were reported in 36% and serious adverse reactions in 29%.


Mogamulizumab-kpkc is a defucosylated, humanized IgG1 kappa monoclonal antibody that binds to CCR4, a G protein-coupled receptor for CC chemokines that is involved in the trafficking of lymphocytes to various organs. Non-clinical in vitro studies demonstrate mogamulizumab-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 T-cell malignancies and is expressed on regulatory T-cells (Treg) and a subset of Th2 T-cells.


Mogamulizumab-kpkc exposure-response relationships and the time course of pharmacodynamics response are unknown.


Mogamulizumab-kpkc pharmacokinetics (PK) was evaluated in patients with T-cell malignancies. Parameters are presented as the geometric mean [% coefficient of variation (%CV)] unless otherwise specified. Mogamulizumab-kpkc concentrations increased proportionally with dose over the dose range of 0.01 to 1.0 mg/kg (0.01 to 1 times the approved recommended dosage).

Following repeated dosing of the approved recommended dosage, steady state concentrations were reached after 8 doses (12 weeks), and the systemic accumulation was 1.6-fold. At steady state, the peak concentration (Cmax,ss) is 32 (68%) μg/mL, the trough concentration (Cmin,ss) is 11 (239%) μg/mL, and AUCss is 5577 (125%) μg•hr/mL.


The central volume of distribution is 3.6 L (20%).


The terminal half-life is 17 days (66%), and the clearance is 12 mL/h (84%).

Specific Populations

No clinically significant changes in the PK of mogamulizumab-kpkc were observed based on age (range: 22 to 101 years), sex, ethnicity, renal impairment (creatinine clearance <90 mL/min, estimated by Cockcroft-Gault), mild (total bilirubin ≤ ULN and AST < ULN, or total bilirubin < 1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) hepatic impairment, disease subtype (MF or SS), degree of CCR4 expression, or ECOG status. The effect of severe hepatic impairment (total bilirubin >3 times ULN and any AST) on mogamulizumab-kpkc PK is unknown.

Drug Interaction Studies

No drug interaction studies have been conducted with mogamulizumab-kpkc.


How Supplied:

POTELIGEO (mogamulizumab-kpkc) injection is a sterile, preservative-free, clear to slightly opalescent colorless solution supplied in a carton containing one 20 mg/5 mL (4 mg/mL), single-dose glass vial (NDC 42747-761-01).

Storage and Handling:

Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in original package to protect from light until time of use. Do not freeze. Do not shake.

Rx only

Rev 08/18