Lartruvo

>10%

Lymphopenia, all grades (77%)

Nausea, all grades (73%)

Fatigue, all grades (69%)

Neutropenia, all grades (65%)

Musculoskeletal pain, all grades (64%)

Thrombocytopenia, all grades (63%)

Mucositis, all grades (53%)

Alopecia, all grades (52%)

Hyperglycemia, all grades (52%)

Neutropenia, grade 3-4 (48%)

Vomiting, all grades (45%)

Lymphopenia, grade 3-4 (44%)

Diarrhea, all grades (34%)

Increased aPTT, all grades (33%)

Decreased appetite, all grades (31%)

Abdominal pain, all grades (23%)

Neuropathy, all grades (22%)

Hypokalemia, all grades (21%)

Hypophosphatemia, all grades (21%)

Headache, all grades (20%)

Increased alkaline phosphatase, all grades (16%)

Hypomagnesemia, all grades (16%)

Infusion-related reactions, all grades (13%)

Anxiety, all grades (11%)

Dry eyes, all grades (11%)

1-10%

Fatigue, grade 3-4 (9%)

Musculoskeletal pain, grade 3-4 (8%)

Hypokalemia, grade 3-4 (8%)

Thrombocytopenia, grade 3-4 (6%)

Increases aPTT, grade 3-4 (5%)

Hypophosphatemia, grade 3-4 (5%)

Abdominal pain, grade 3-4 (3%)

Diarrhea, grade 3-4 (3%)

Mucositis, grade 3-4 (3%)

Infusion-related reactions, grade 3-4 (3%)

Nausea, grade 3-4 (2%)

Decreased appetite, grade 3-4 (2%)

Hyperglycemia, grade 3-4 (2%)

IV Compatibilities

0.9% NaCl

IV Incompatibilities

Dextrose-containing solutions

Electrolyte-containing solutions (eg, Ringers Lactate)

IV Preparation

Solution in unopened vial should appear clear to slightly opalescent, colorless to slightly yellow

Inspect vial contents for particulate matter and discoloration prior to dilution; discard if particulate matter or discolorations is identified

Withdraw calculated dose and further dilute with 0.9% NaCl to a final volume of 250 mL for IV infusion; do not use dextrose-containing or other solutions

Gently invert but do not shake

Do not freeze the diluted solution

Store the diluted solution for up to 24 hr under refrigeration at 2-8°C (36-46°F) and for up to an additional 4 hr at room temperature (<25°C [77°F])

Storage times include the duration of infusion; if refrigerated, allow the diluted solution to come to room temperature before administration

Discard vial with any unused portion

IV Administration

Premedication

• Premedicate with diphenhydramine (25-50 mg IV) and dexamethasone (10-20 mg IV) before olaratumab dose on Day 1 of cycle 1

Intravenous infusion

• Do not administer as IV push or bolus
• Do not infuse with electrolytes or other medications through the same IV line
• Visually inspect the diluted solution for particulate matter and discoloration prior to administration; if particulate matter or discolorations is identified, discard the solution
• Administer diluted solution as an IV infusion over 1 hr
• Flush the line with 0.9% NaCl at end of infusion

Storage

Unopened vial

• Preservative-free solution
• Refrigerate at 2-8°C (36-46°F) until time of use
• Keep the vial in the outer carton to protect from light
• Do not freeze
• Do not shake vial

Diluted solution

• Refrigerate for up to 24 hr at 2-8°C (36-46°F) and for up to an additional 4 hr at room temperature (<25°C [77°F])
• Do not freeze
• Do not shake diluted solution

Mechanism Of Action

Olaratumab is a human IgG1 antibody that binds platelet-derived growth factor receptor alpha (PDGFR-α). PDGFR-α is a receptor tyrosine kinase expressed on cells of mesenchymal origin. Signaling through this receptor plays a role in cell growth, chemotaxis, and mesenchymal stem cell differentiation. The receptor has also been detected on some tumor and stromal cells, including sarcomas, where signaling can contribute to cancer cell proliferation, metastasis, and maintenance of the tumor microenvironment. The interaction between olaratumab and PDGFR-α prevents binding of the receptor by the PDGF-AA and -BB ligands as well as PDGF-AA, -BB, and -CC-induced receptor activation and downstream PDGFR-α pathway signaling. Olaratumab exhibits in vitro and in vivo anti-tumor activity against selected sarcoma cell lines and disrupted the PDGFR-α signaling pathway in in vivo tumor implant models.

Pharmacodynamics

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

Pharmacokinetics

The volume of distribution (CV%) at steady-state (Vss) is 7.7 L (16%).

The mean clearance (CV%) for olaratumab was 0.56 L/day (33%). The estimated elimination half-life was approximately 11 days (range 6 to 24 days).

Specific Populations

Age (22 to 85 years), sex (47% females), race (86% Whites), mild to moderate renal impairment [calculated creatinine clearance (CLcr) 30-89 mL/min as estimated by the Cockcroft-Gault formula (C-G)], and mild [total bilirubin within upper limit of normal (ULN) and AST greater than ULN or total bilirubin greater than 1.0 and up to 1.5 times ULN and any AST] to moderate (total bilirubin greater than 1.5 and up to 3.0 times ULN and any AST) hepatic impairment had no clinically important effect on the pharmacokinetics of olaratumab. The pharmacokinetics of olaratumab in patients with severe renal impairment (CLcr 15-29 mL/min as estimated by C-G) or with severe hepatic impairment (total bilirubin greater than 3.0 times ULN and any AST) are unknown. Body weight (range 37 to 151 kg) correlates with clearance and volume of distribution of olaratumab.

Drug Interaction Studies

No clinically relevant changes in the exposure of either olaratumab or doxorubicin were observed when LARTRUVO 15 mg/kg and doxorubicin 75 mg/m² were co-administered in patients with solid tumors.

Clinical Studies

The efficacy of LARTRUVO was demonstrated in Trial 1, an open-label, randomized, active-controlled study. Eligible patients were required to have soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy, a histologic type of sarcoma for which an anthracycline-containing regimen was appropriate but had not been administered, ECOG PS of 0-2, and tumor specimen available for assessment of PDGFR-α expression by an investigational use assay. Patients were randomized (1:1) to receive LARTRUVO in combination with doxorubicin or doxorubicin as a single agent. PDGFR-α expression (positive versus negative), number of previous lines of treatment (0 versus 1 or more), histological tumor type (leiomyosarcoma versus synovial sarcoma versus all others), and ECOG PS (0 or 1 versus 2) were used to allocate patients in the randomization. LARTRUVO was administered at 15 mg/kg as an intravenous infusion on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity. All patients received doxorubicin 75 mg/m² as an intravenous infusion on Day 1 of each 21-day cycle for a maximum of eight cycles and were permitted to receive dexrazoxane prior to doxorubicin in Cycles 5 to 8. Patients randomized to receive doxorubicin as a single agent were offered LARTRUVO at the time of disease progression. The efficacy outcome measures were overall survival (OS), and progression-free survival (PFS) and objective response rate (ORR) as assessed by investigator and by independent review according to RECIST v1.1.

A total of 133 patients were randomized, 66 patients to the LARTRUVO plus doxorubicin arm and 67 patients to the doxorubicin arm. Baseline demographics and disease characteristics were: median age of 58 years (range 22 to 86); 44% men; 86% White, 8% Black, 3% Asian, and 2% Other; 56% ECOG PS 0 and 39% ECOG PS 1; 65% no prior chemotherapy (excluding adjuvant and neoadjuvant therapy); 38% leiomyosarcoma, 1.5% synovial sarcoma, and 61% other histologies [17% liposarcoma (8% dedifferentiated, 4% myxoid, 3% well-differentiated, 1.5% pleomorphic, 1% liposarcoma not otherwise specified (NOS)), 11% undifferentiated pleomorphic sarcoma, 5% angiosarcoma, 5% undifferentiated sarcoma NOS, 3% extraskeletal myxoid chondrosarcoma, 2% malignant peripheral nerve sheath tumor, 2% myxofibrosarcoma, 2% malignant solitary fibrous tumor, 2% endometrial stromal sarcoma, 1.5% chondrosarcoma, 1.5% epithelioid sarcoma, 1.5% fibrosarcoma, 1.5% low-grade fibromyxoid sarcoma, and 5% other histologies with one patient each]. All patients had metastatic disease and were enrolled at U.S. sites. Among patients randomized to doxorubicin, 30 (45%) patients received LARTRUVO as a single agent at the time of disease progression.

Trial 1 demonstrated a significant improvement in overall survival. The efficacy results are summarized in Table 3 and Figure 1.

Table 3: Efficacy Results in Trial 1

Figure 1: Kaplan-Meier Curves of Overall Survival

Do not take Lartruvo if you are pregnant or plan to become pregnant in the next 3 months. 

It has been shown that women taking Lartruvo during pregnancy may have babies born with serious problems. There are no situations where the benefits of the medication for the mother outweigh the risks of harm to the baby. These medicines should never be used by pregnant women.

Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant during your treatment with Lartruvo and for 3 months after your final dose. Talk to your doctor about birth control methods that you can use during your treatment. If you become pregnant while being treated with Lartruvo, call your doctor.

Olaratumab is a monoclonal antibody that blocks a certain type of cell receptor in the body that can affect tumor cell growth. Monoclonal antibodies are made to target and destroy only certain cells in the body, which may help slow or stop tumor growth.

Olaratumab is used in combination with another cancer medicine called doxorubicin, to treat adults with soft tissue sarcoma. Olaratumab is used when your condition cannot be treated with surgery or radiation.

Olaratumab was approved by the US Food and Drug Administration (FDA) on an "accelerated" basis. In clinical studies, this medicine was shown to lengthen survival time. However, further studies are needed to determine if olaratumab is effective in larger numbers of patients with soft tissue sarcoma.

Olaratumab may also be used for purposes not listed in this medication guide.

Olaratumab can cause an infusion reaction during the injection. Tell your caregiver right away if you feel dizzy, light-headed, chilled, flushed, feverish, or short of breath.

You should not receive olaratumab if you are pregnant. Avoid pregnancy for at least 3 months after you stop using this medicine.

You should not be treated with olaratumab if you are allergic to it.

To make sure olaratumab is safe for you, tell your doctor if you have:

• diabetes; or
• an electrolyte imbalance (such as low levels of potassium in your blood).

You should not receive olaratumab if you are pregnant. It could harm the unborn baby or cause birth defects. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 3 months after your last dose.

It is not known whether olaratumab passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, light-headed, chilled, flushed, feverish, or short of breath, or if you have a cold sweat, chest tightness, or trouble breathing.

Call your doctor at once if you have:

• sores or white patches in or around your mouth, trouble swallowing or talking, dry mouth, bad breath, altered sense of taste;
• easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
• fever, cough, cold or flu symptoms;
• swollen gums;
• skin sores; or
• trouble breathing.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

• nausea, vomiting, stomach pain, diarrhea, loss of appetite;
• feeling tired;
• muscle or joint pain;
• numbness, weakness, or pain in your hands or feet;
• hair loss; or
• headache.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Olaratumab is injected into a vein through an IV. A healthcare provider will give you this injection.

Olaratumab is given in a 21-day treatment cycle. You may receive the medicine only during the first 2 weeks of each cycle, on Day 1 and Day 8 of the full cycle.

The day before you receive olaratumab, you may be given other IV medications to prevent certain side effects.

Olaratumab must be given slowly, and the IV infusion can take at least 60 minutes to complete.

For the first 8 treatment cycles, you will also be treated with doxorubicin.

Read all patient information and medication guides provided to you for each of your medications. Ask your doctor or pharmacist if you have any questions.

Your doctor will determine how long to treat you with olaratumab.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Call your doctor for instructions if you miss an appointment for your olaratumab injection.

Olaratumab is a monoclonal antibody that blocks a certain type of cell receptor in the body that can affect tumor cell growth. Monoclonal antibodies are made to target and destroy only certain cells in the body, which may help slow or stop tumor growth.

Olaratumab is used in combination with another cancer medicine called doxorubicin, to treat adults with soft tissue sarcoma. Olaratumab is used when your condition cannot be treated with surgery or radiation.

Olaratumab was approved by the US Food and Drug Administration (FDA) on an "accelerated" basis. In clinical studies, this medicine was shown to lengthen survival time. However, further studies are needed to determine if olaratumab is effective in larger numbers of patients with soft tissue sarcoma.

Olaratumab may also be used for purposes not listed in this medication guide.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

A nurse or other trained health professional will give you this medicine in a hospital. This medicine is given through a needle placed in one of your veins.

This medicine is usually given on Day 1 and Day 8 of a 21-day cycle treatment. For the first 8 cycles, it is given in combination with doxorubicin. Each treatment usually takes about 60 minutes.

If you will be using this medicine for a long time, it is very important that your doctor check you at regular visits for any unwanted effects from the medicine.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during treatment and for 3 months after the last dose of this medicine. If you think you have become pregnant while using the medicine, tell your doctor right away.

This medicine may cause a rare but serious type of an allergic reaction called an infusion related reaction. This can be life-threatening and requires immediate medical attention. Tell your doctor right away if you start to have cough, difficulty with swallowing, dizziness, fast heartbeat, trouble breathing, chest tightness, swelling in your face or hands, fever, chills, itching or hives, or lightheadedness or faintness while you are receiving this medicine.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Mouth irritation or mouth sores.
• Loose stools (diarrhea).
• Not hungry.
• Stomach pain.
• Feeling tired or weak.
• Muscle pain.
• Hair loss.
• Headache.
• Anxiety.
• Dry eyes.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Injection: 500 mg/50 mL (10 mg/mL) or 190 mg/19 mL (10 mg/mL) clear to slightly opalescent, colorless to slightly yellow solution in a single-dose vial.

Mechanism of Action

Olaratumab is a human IgG1 antibody that binds platelet-derived growth factor receptor alpha (PDGFR-α). PDGFR-α is a receptor tyrosine kinase expressed on cells of mesenchymal origin. Signaling through this receptor plays a role in cell growth, chemotaxis, and mesenchymal stem cell differentiation. The receptor has also been detected on some tumor and stromal cells, including sarcomas, where signaling can contribute to cancer cell proliferation, metastasis, and maintenance of the tumor microenvironment. The interaction between olaratumab and PDGFR-α prevents binding of the receptor by the PDGF-AA and -BB ligands as well as PDGF-AA, -BB, and -CC-induced receptor activation and downstream PDGFR-α pathway signaling. Olaratumab exhibits in vitro and in vivo anti-tumor activity against selected sarcoma cell lines and disrupted the PDGFR-α signaling pathway in in vivo tumor implant models.

Pharmacodynamics

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

Pharmacokinetics

Distribution

The volume of distribution (CV%) at steady-state (Vss) is 7.7 L (16%).

Elimination

The mean clearance (CV%) for olaratumab was 0.56 L/day (33%). The estimated elimination half-life was approximately 11 days (range 6 to 24 days).

Specific Populations

Age (22 to 85 years), sex (47% females), race (86% Whites), mild to moderate renal impairment [calculated creatinine clearance (CLcr) 30-89 mL/min as estimated by the Cockcroft-Gault formula (C-G)], and mild [total bilirubin within upper limit of normal (ULN) and AST greater than ULN or total bilirubin greater than 1.0 and up to 1.5 times ULN and any AST] to moderate (total bilirubin greater than 1.5 and up to 3.0 times ULN and any AST) hepatic impairment had no clinically important effect on the pharmacokinetics of olaratumab. The pharmacokinetics of olaratumab in patients with severe renal impairment (CLcr 15-29 mL/min as estimated by C-G) or with severe hepatic impairment (total bilirubin greater than 3.0 times ULN and any AST) are unknown. Body weight (range 37 to 151 kg) correlates with clearance and volume of distribution of olaratumab.

Drug Interaction Studies

No clinically relevant changes in the exposure of either olaratumab or doxorubicin were observed when Lartruvo 15 mg/kg and doxorubicin 75 mg/m2 were co-administered in patients with solid tumors.

Lartruvo is supplied in single-dose vials as a sterile, preservative-free, clear to slightly opalescent and colorless to slightly yellow solution.

• NDC 0002-7190-01
  190 mg/19 mL (10 mg/mL) single-dose vial, individually packaged in a carton
• NDC 0002-8926-01
  500 mg/50 mL (10 mg/mL) single-dose vial, individually packaged in a carton

Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) until time of use. Keep the vial in the outer carton to protect from light. DO NOT FREEZE OR SHAKE the vial.