Margetuximab is a chimeric Fc-engineered IgG1 kappa monoclonal antibody against the HER2 protein. It is indicated in combination with chemotherapy for the treatment of metastatic HER2-positive breast cancer in patients who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Treatment with margetuximab plus chemotherapy significantly improved progression-free survival (PFS) compared with trastuzumab plus chemotherapy in a multicenter, randomized, open-label clinical trial (the SOPHIA study). Treatment with margetuximab can cause heart failure, with the highest incidence in patients receiving concomitant therapy with anthracyclines; monitor left ventricular function in all patients.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Some visible, translucent, inherent proteinaceous particles may be present.
Intravenous Administration
-Administer as an intravenous infusion; do not administer IV push or as a bolus.
-Calculate the dose based on patient body weight; round to the nearest 0.1 mL.
-Do NOT mix or dilute with other drugs or dextrose solutions. Do not administer other drugs through the same infusion line.
-Administer through an IV line containing a sterile, non-pyrogenic, low protein binding polyethersulfone (PES) 0.2 micron in-line or add-on filter.
-If a patient misses a dose, administer it as soon as possible. Adjust the administration schedule to maintain a 3-week interval between doses.
Dilution
-Gently swirl the vial of margetuximab; do not shake.
-Withdraw the appropriate volume of margetuximab from the vial and add to 100 mL or 250 mL of 0.9% Sodium Chloride Injection for a final concentration of 0.5 mg/mL to 7.2 mg/mL.
-Polyvinylchloride (PVC) intravenous bags or those made with polyolefins (polyethylene and polypropylene) and polyamide, polyolefins only, or copolymer of olefins may be used. Do not use 5% Dextrose Injection.
-Gently invert the bag to mix the solution; do not shake.
-Discard any unused portion left in the vial.
Storage after dilution
-Diluted solutions can be stored at room temperature for up to 4 hours or refrigerated (2 to 8 degrees Celsius; 36 to 46 degrees Fahrenheit) for up to 24 hours. Do not freeze.
-If stored under refrigeration, allow the diluted solution to come to room temperature prior to administration.
Left ventricular dysfunction (heart failure) occurred in 1.9% of advanced breast cancer patients treated with margetuximab in a multicenter, randomized, open-label clinical trial. Potential cardiotoxicity was more common in patients 65 years of age or older compared to younger patients (35% vs. 18%). An interruption or discontinuation of therapy may be necessary for a decrease in left ventricular ejection fraction (LVEF).
Infusion-related reactions occurred in 13% of patients who received margetuximab in a multicenter, randomized, open-label clinical trial (grade 3, 1.5%). Infusion reactions resulted in an interruption of therapy in 9% of patients treated with margetuximab; one patient (0.4%) discontinued therapy. All infusion reactions, regardless of severity, resolved within 24 hours. In an infusion sub-study (n = 88), infusion-related reactions were grade 2 or less, and most occurred during the first (2 hours) infusion; from cycle 2 onward, one patient (1.1%) had an infusion reaction (grade 1). Monitor patients for infusion reactions during margetuximab administration and as clinically indicated after the completion of infusion. Decrease the infusion rate for mild or moderate infusion reactions; interrupt the infusion in patients experiencing dyspnea or clinically significant hypotension. Permanently discontinue margetuximab in patients with severe or life-threatening infusion reactions.
Fatigue/asthenia occurred in 57% of patients with advanced breast cancer treated with margetuximab compared with 47% of those who received trastuzumab in a randomized, open-label clinical trial (grade 3 or 4, 7% vs. 4.5%).
Fever occurred in 19% of patients with advanced breast cancer treated with margetuximab compared with 14% of those who received trastuzumab in a randomized, open-label clinical trial (grade 3 or 4, 0.4% vs. 0.4%). Neutropenic fever occurred in 1.5% of margetuximab-treated patients.
Nausea was reported in 33% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial (grade 3 or 4, 1.1%); vomiting occurred in 21% of these patients (grade 3 or 4, 0.8%).
Diarrhea was reported in 25% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial (grade 3 or 4, 2.3%).
Constipation was reported in 19% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial (grade 3 or 4, 0.8%).
Abdominal pain was reported in 17% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial (grade 3 or 4, 1.5%).
Anorexia was reported in 14% (grade 3 or 4, 0.4%) and dysgeusia in 6% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial. Weight loss was reported in 6% of margetuximab-treated patients.
Stomatitis was reported in 10% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial.
Alopecia was reported in 18% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial.
Palmar-plantar erythrodysesthesia (hand and foot syndrome) occurred in 13% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial. A generalized rash was reported in 6% of margetuximab-treated patients. Rash, pruritus, and urticaria were also described as manifestations of infusion reactions.
Headache (including migraine) was reported in 19% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial.
Peripheral neuropathy including peripheral sensory and motor neuropathy was reported in 16% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial (grade 3 or 4, 1.1%).
Dizziness was reported in 10% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial. Syncope occurred in 1.5% of margetuximab-treated patients.
Cough was reported in 14% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial (grade 3 or 4, 0.4%). Dyspnea occurred in 13% of these patients (grade 3 or 4, 1.1%).
Arthralgia/myalgia was reported in 14% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial (grade 3 or 4, 0.4%). Extremity pain was additionally reported in 11% of margetuximab-treated patients (grade 3 or 4, 0.8%).
Insomnia was reported in 6% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial.
Hypertension was reported in 5% of patients with advanced breast cancer treated with margetuximab in a randomized, open-label clinical trial.
Hematologic adverse reactions have been reported with margetuximab therapy including anemia, leukopenia, neutropenia, and lymphopenia. In a randomized, open-label clinical trial comparing margetuximab plus chemotherapy to trastuzumab plus chemotherapy in patients with advanced breast cancer, decreased hemoglobin (52% vs. 43%; grade 3 or 4, 3.2% vs. 2.4%), decreased leukocytes (40% vs. 36%; grade 3 or 4, 5% vs. 3.2%), decreased neutrophils (34% vs. 28%; grade 3 or 4, 9% vs. 9%), and decreased lymphocytes (31% vs. 38%; grade 3 or 4, 4.4% vs. 4.4%) were reported compared to baseline.
Prolonged bleeding time has been reported in patients with advanced breast cancer treated with margetuximab plus chemotherapy, although the incidences of increased aPTT (32% vs. 34%; grade 3 or 4, 3.4% vs. 4.3%) and increased INR (24% vs. 25%; grade 3 or 4, 1.2% vs. 0.4%) were similar to patients who received trastuzumab plus chemotherapy in a randomized, open-label trial.
Elevated hepatic enzymes have been reported in patients with advanced breast cancer treated with margetuximab plus chemotherapy in a randomized, open-label trial including increases in ALT compared to baseline (32%; grade 3 or 4, 2%), increased AST (23%; grade 3 or 4, 2%), and increased alkaline phosphatase (21%). Other chemistry abnormalities included increased lipase concentrations (30%; grade 3 or 4, 6%) and increased creatinine (68%; grade 3 or 4, 0.4%).
Treatment-emergent anti-margetuximab antibody formation occurred in 4 patients (1.7%) who received margetuximab in a randomized, open-label clinical trial; all patients had previously received trastuzumab. Of these patients, anti-margetuximab antibodies were detected prior to cycle 7 in 1 patient and more than 2 months after the last dose of margetuximab in 3 patients. In an infusion sub-study, treatment-emergent anti-margetuximab antibodies were observed in 2 patients (3.8%): prior to cycle 3 in one patient and more than 6 months after the last dose in the other patient. Due to the limited number of patients, the impact of anti-margetuximab antibodies on the pharmacokinetics, safety, and efficacy of margetuximab is unknown.
Use margetuximab with caution in patients with a history of cardiac disease. Left ventricular dysfunction (heart failure) occurred in patients with advanced breast cancer who received margetuximab in a multicenter, randomized, open-label clinical trial; margetuximab has not been studied in patients with a pretreatment left ventricular ejection fraction (LVEF) of less than 50%, a prior history of myocardial infarction, unstable angina within 6 months, or New York Heart Association (NYHA) class II to IV congestive heart failure. Conduct a thorough cardiac assessment including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan at baseline (within 4 weeks prior to initiation of therapy), every 3 weeks during therapy, and upon completion of therapy. An interruption or discontinuation of therapy may be necessary for a decline in LVEF. Based on clinical data from other HER2-directed antibodies, patients who receive anthracycline therapy less than 4 months after stopping margetuximab may be at increased risk of cardiac dysfunction.
Administration of margetuximab can result in infusion-related reactions characterized by fever and chills, nausea, vomiting, headache, dizziness, arthralgia, cough, fatigue, diaphoresis, tachycardia, dyspnea, hypotension, rash, pruritus, and urticaria. Most of the infusion-related reactions in a multicenter, randomized, open-label trial occurred during cycle 1. Monitor patients for infusion reactions during margetuximab administration and as clinically indicated after the completion of infusion. Have medications to treat infusion reactions (e.g., epinephrine, corticosteroids, diphenhydramine, bronchodilators and oxygen) as well as emergency equipment available for immediate use. Decrease the infusion rate for mild or moderate infusion reactions; interrupt the infusion in patients experiencing dyspnea or clinically significant hypotension. If infusion reactions occur, monitor carefully until resolution. Consider premedications for subsequent infusions in these patients, including antihistamines, corticosteroids, and antipyretics. Permanently discontinue margetuximab in patients with severe or life-threatening infusion reactions.
Closely monitor geriatric patients for margetuximab-related adverse reactions. Patients older than 65 years of age who received margetuximab had an increased incidence of grade 3 or higher adverse reactions compared to younger patients (56% vs. 47%); potential cardiotoxicity was also more common in older patients (35% vs. 18%).
Pregnancy should be avoided by females of reproductive potential during margetuximab treatment and for at least 4 months after the last dose. If a woman becomes pregnant while receiving margetuximab or within 4 months of the last dose, inform her of the fetal risks and monitor for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and is consistent with community standards of care. Although there are no adequately controlled studies in pregnant women, margetuximab can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Oligohydramnios and oligohydramnios sequence (manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death) have been reported in postmarketing experience in pregnant women who received HER2-directed antibody treatment. In an animal reproduction study, oligohydramnios and delayed infant kidney development occurred after IV margetuximab administration to pregnant cynomolgus monkeys starting at gestational day 20 until delivery; animal exposures were at least 3 times the human exposures at the recommended dose. Clinical findings included tubular degeneration/necrosis and tubular dilatation in the kidney. Maternal doses of 50 and 100 mg/kg resulted in decreased infant kidney weights and histologic immature nephrons. Measurable serum concentrations of margetuximab were observed in infant animals, which is consistent with margetuximab crossing the placenta.
Counsel patients about the reproductive risk and contraception requirements during margetuximab treatment. Margetuximab can be teratogenic if taken by the mother during pregnancy. Females should avoid pregnancy and use effective contraception during and for at least 4 months after treatment with margetuximab. Females of reproductive potential should undergo pregnancy testing prior to initiation of margetuximab. Women who become pregnant while receiving margetuximab should be apprised of the potential hazard to the fetus.
Due to the potential for serious adverse reactions in nursing infants from margetuximab, advise women to discontinue breast-feeding during treatment and for 4 months after the final dose. It is not known whether margetuximab is present in human milk, although many drugs are excreted in human milk. Published data suggest human IgG is present in human milk but does not enter the neonatal and infant circulation in substantial amounts.
For the treatment of breast cancer:
-for the treatment of metastatic HER2-positive breast cancer, in combination with chemotherapy, in patients who have received at least 2 prior anti-HER2 regimens, at least one of which was for metastatic disease:
Intravenous dosage:
Adults: 15 mg/kg IV every 3 weeks until disease progression or unacceptable toxicity, in combination with chemotherapy. Administer the first dose over 2 hours and then subsequent doses may be infused over at least 30 minutes. Administer margetuximab immediately after the completion of chemotherapy when margetuximab and chemotherapy are administered on the same day. Treatment with margetuximab plus chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine) significantly improved the median progression-free survival (PFS) compared with trastuzumab plus chemotherapy in a multicenter, randomized, open-label clinical trial (the SOPHIA study) for a median of 5.8 months for a median duration of 6.1 months, versus 4.9 months for a median duration of 6 months, respectively. The objective response rate for patients with measurable disease was 22% in the margetuximab arm compared with 16% in the trastuzumab arm. Overall survival was not significantly different in the margetuximab arm (21.6 months vs. 21.9 months).
Therapeutic Drug Monitoring:
Dosage Adjustments for Treatment-Related Toxicities
Infusion-Related Reactions
-Mild or moderate reactions: Decrease the rate of the margetuximab infusion. Interrupt the margetuximab infusion for dyspnea or clinically significant hypotension. Monitor carefully until resolution. Consider premedications including antihistamines, corticosteroids, and antipyretics for subsequent infusions.
-Severe or life-threatening reactions: Permanently discontinue margetuximab.
Left Ventricular Dysfunction
-16% or greater absolute decrease in left ventricular ejection fraction (LVEF) from baseline: Hold margetuximab for at least 4 weeks. Repeat LVEF every 4 weeks. If LVEF returns to normal limits within 8 weeks and the absolute decrease from baseline is 15% or less, margetuximab treatment may be resumed. Permanently discontinue margetuximab if the LVEF decline persists for greater than 8 weeks, or if dosing is interrupted more than 3 times for LVEF decline.
-LVEF below the institutional limits of normal (50% if no limits are available) and 10% or greater absolute decrease in LVEF from baseline: Hold margetuximab for at least 4 weeks. Repeat LVEF every 4 weeks. If LVEF returns to normal limits within 8 weeks and the absolute decrease from baseline is 15% or less, margetuximab treatment may be resumed. Permanently discontinue margetuximab if the LVEF decline persists for greater than 8 weeks, or if dosing is interrupted more than 3 times for LVEF decline.
-Clinically significant confirmed decrease in LVEF: Discontinue margetuximab.
Maximum Dosage Limits:
-Adults
15 mg/kg IV every 3 weeks.
-Geriatric
15 mg/kg IV every 3 weeks.
-Adolescents
Safety and effectiveness have not been established.
-Children
Safety and effectiveness have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. The effect of moderate (total bilirubin 1.6 to 3 times ULN and any AST) or severe hepatic impairment (total bilirubin greater than 3 times ULN and any AST) on the pharmacokinetics of margetuximab is unknown.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. The effect of severe renal impairment (CrCl 15 to 29 mL/min) and end-stage renal disease with or without hemodialysis on the pharmacokinetics of margetuximab is unknown.
*non-FDA-approved indication
Anthracyclines: (Major) Avoid administration of anthracyclines during margetuximab therapy and for up to 4 months after the last dose of margetuximab due to the risk of increased cardiac dysfunction. If concomitant use is unavoidable, closely monitor cardiac function. This interaction has not been studied with margetuximab; however, clinical data from other HER2-directed antibodies warrants consideration.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Daunorubicin Liposomal; Cytarabine Liposomal: (Major) Avoid administration of anthracyclines during margetuximab therapy and for up to 4 months after the last dose of margetuximab due to the risk of increased cardiac dysfunction. If concomitant use is unavoidable, closely monitor cardiac function. This interaction has not been studied with margetuximab; however, clinical data from other HER2-directed antibodies warrants consideration.
Daunorubicin: (Major) Avoid administration of anthracyclines during margetuximab therapy and for up to 4 months after the last dose of margetuximab due to the risk of increased cardiac dysfunction. If concomitant use is unavoidable, closely monitor cardiac function. This interaction has not been studied with margetuximab; however, clinical data from other HER2-directed antibodies warrants consideration.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Doxorubicin Liposomal: (Major) Avoid administration of anthracyclines during margetuximab therapy and for up to 4 months after the last dose of margetuximab due to the risk of increased cardiac dysfunction. If concomitant use is unavoidable, closely monitor cardiac function. This interaction has not been studied with margetuximab; however, clinical data from other HER2-directed antibodies warrants consideration.
Doxorubicin: (Major) Avoid administration of anthracyclines during margetuximab therapy and for up to 4 months after the last dose of margetuximab due to the risk of increased cardiac dysfunction. If concomitant use is unavoidable, closely monitor cardiac function. This interaction has not been studied with margetuximab; however, clinical data from other HER2-directed antibodies warrants consideration.
Epirubicin: (Major) Avoid administration of anthracyclines during margetuximab therapy and for up to 4 months after the last dose of margetuximab due to the risk of increased cardiac dysfunction. If concomitant use is unavoidable, closely monitor cardiac function. This interaction has not been studied with margetuximab; however, clinical data from other HER2-directed antibodies warrants consideration.
Idarubicin: (Major) Avoid administration of anthracyclines during margetuximab therapy and for up to 4 months after the last dose of margetuximab due to the risk of increased cardiac dysfunction. If concomitant use is unavoidable, closely monitor cardiac function. This interaction has not been studied with margetuximab; however, clinical data from other HER2-directed antibodies warrants consideration.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Margetuximab is a chimeric Fc-engineered IgG1 kappa monoclonal antibody that selectively binds to the extracellular domain of HER2. Overexpression of HER2 in tumor cells is closely associated with increased angiogenesis and expression of vascular epidermal growth factor (VEGF); when the VEGF pathway is inhibited, tumor growth is suppressed. After binding to HER2-expressing cells, margetuximab inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain, and mediates antibody-dependent cellular cytotoxicity (ADCC). In vitro, the modified Fc region of margetuximab increases binding to activating Fc receptor FCGR3A (CD16A) and decreases binding to inhibitor Fc receptor FCGR2B (CD32B). These changes lead to greater in vitro ADCC and NK cell activation.
Margetuximab is administered intravenously. The geometric mean volume of distribution at steady-state is 5.47 liters (CV, 22%). The geometric mean terminal half-life of margetuximab is 19.2 days (CV, 28%) and the time to steady-state was 2 months. The geometric mean clearance of margetuximab is 0.22 liters per day (CV, 24%); it undergoes both linear and nonlinear elimination. Concentrations continued to decrease to approximately 3% of the steady-state trough serum concentration four months after margetuximab discontinuation.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None.
Margetuximab is expected to be metabolized into small peptides by catabolic pathways.
-Route-Specific Pharmacokinetics
Intravenous Route
After administration at the recommended dose, the geometric mean Cmax of margetuximab at steady-state is 466 mcg/mL (CV, 20%) and the AUC is 4,120 mcg x day/mL (CV, 21%) in patients with HER2-positive relapsed or refractory advanced breast cancer; the accumulation ratio was 1.65 based on AUC. After a single dose, the Cmax and AUC of margetuximab increase in an approximately dose proportional manner from 10 to 18 mg/kg (0.67 to 1.2 times the recommended dose). No clinically significant differences in margetuximab exposure were observed when the infusion time was reduced from 120 minutes to 30 minutes.
-Special Populations
Hepatic Impairment
Mild hepatic impairment (total bilirubin at the upper limit of normal (ULN) or less and AST greater than ULN; or total bilirubin 1 to 1.5 times ULN and any AST) did not have a clinically significant effect on the pharmacokinetics of margetuximab. The effect of moderate or severe hepatic impairment (total bilirubin greater than 1.5 times ULN and any AST) on the pharmacokinetics of margetuximab is unknown.
Renal Impairment
Mild to moderate renal impairment (CrCl 30 to 89 mL/min) did not have a clinically significant effect on the pharmacokinetics of margetuximab. The effect of severe renal impairment (CrCl 15 to 29 mL/min) and end-stage renal disease with or without hemodialysis on the pharmacokinetics of margetuximab is unknown.
Geriatric
Age (29 to 83 years) did not have a clinically significant effect on the pharmacokinetics of margetuximab.
Gender Differences
Sex did not have a clinically significant effect on the pharmacokinetics of margetuximab.
Ethnic Differences
Ethnicity (Caucasian patients, Black patients, Asian patients) did not have a clinically significant effect on the pharmacokinetics of margetuximab.
Other
HER2 expression level (0 to 3 by IHC), tumor burden (2 to 317 mm), ECOG score (0 to 2), albumin (24 to 50 g/liter), FCGR3A (CD16A), FCGR2A (CD32A) and FCGR2B (CD32B) genotype, number of metastatic sites (2 or less, or more than 2), number of prior therapy lines 2 or less, or more than 2 or concurrent chemotherapies (capecitabine, gemcitabine, eribulin and vinorelbine) did not have a clinically significant effect on the pharmacokinetics of margetuximab.