Lartruvo

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 

 
 

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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Lartruvo 10 mg/mL concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One mL of concentrate for solution for infusion contains 10 mg of olaratumab. 
 
Each 19 mL vial contains 190 mg of olaratumab. 
Each 50 mL vial contains 500 mg of olaratumab. 
 
Olaratumab is a human IgG1 monoclonal antibody produced in murine (NS0) cells by recombinant 
DNA technology. 
 
Excipient with known effect 
 
Each 19mL vial contains approximately 22 mg (1 mmol) sodium. 
Each 50 mL vial contains approximately 57 mg (2.5 mmol) sodium. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion (sterile concentrate). 
 
The concentrate is clear to slightly opalescent and colourless to slightly yellow solution without visible 
particles.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Lartruvo is indicated in combination with doxorubicin for the treatment of adult patients with 
advanced soft tissue sarcoma who are not amenable to curative treatment with surgery or radiotherapy 
and who have not been previously treated with doxorubicin (see section 5.1). 
 
4.2 Posology and method of administration 
 
Olaratumab therapy must be initiated and supervised by physicians experienced in oncology. Patients 
should be monitored during the infusion for signs and symptoms of infusion-related reactions (IRRs) 
in a setting with available resuscitation equipment (see section 4.4). 
 
Posology 
 
The recommended dose of olaratumab is 15 mg/kg administered by intravenous infusion on days 1 
and 8 of each 3 week cycle until disease progression or unacceptable toxicity. Lartruvo is administered 
in combination with doxorubicin for up to 8 cycles of treatment, followed by Lartruvo monotherapy in 

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patients whose disease has not progressed. Doxorubicin is given on day 1 of each cycle following the 
Lartruvo infusion. 
 
Premedication 
Premedication with an H1 antagonist (e.g., diphenhydramine) and dexamethasone (or equivalent 
medicinal products) should be given, intravenously, 30–60 minutes prior to the olaratumab doses on 
days 1 and 8 of cycle 1 in all patients. For subsequent cycles, premedication with an H1 antagonist 
(e.g., diphenhydramine) should be given intravenously 30–60 minutes prior to each dose of 
olaratumab.  
 
For patients who experience Grade 1 or 2 IRR, the infusion should be interrupted and paracetamol, 
H1 antagonist and dexamethasone (or equivalent medicinal products) administered as needed. For all 
subsequent infusions, premedication with the following (or equivalent medicinal products) 
diphenhydramine hydrochloride (intravenously), paracetamol, and dexamethasone, should be given.  
 
In the event that intravenous administration of an H1 antagonist is not possible, equivalent alternative 
premedication should be given (e.g. oral diphenhydramine hydrochloride at least 90 minutes prior to 
the infusion).   
  
Posology adjustments for olaratumab 
For dose adjustment recommendations related to doxorubicin, refer to the current doxorubicin 
prescribing information.  
 
Infusion-related reactions (IRRs) 
Recommendations for the management of olaratumab IRRs are provided in table 1. 
 

Table 1 – Management recommendations for infusion-related reactions (IRRs) 
 

Toxicity 
gradea 

Management recommendations 
(any occurrence) 

Grade 1-2 • Stop the infusion 
• Paracetamol, H1 antagonist and dexamethasone should be 

administered as needed (see premedication section)  
• Once the reaction has resolved, resume infusion at a 50 % 

decreased infusion rate.b 
• Monitor patient for worsening of condition. 
• For subsequent infusions, please see premedication section. 

Grade 3-4 • Immediately and permanently discontinue treatment with 
olaratumab (see section 4.4). 

a Grade per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI 
CTCAE), Version 4.03 
b Once the infusion rate has been reduced for a Grade 1 or 2 infusion-related reaction, it is 
recommended that the lower infusion rate be utilized for all subsequent infusions. The infusion 
duration should not exceed 2 hours. 

 
Other non-haematology toxicities 
For serious Grade ≥ 3 non-haematologic toxicity deemed related to olaratumab, the dose of olaratumab 
should be withheld until toxicity is ≤ Grade 1 or has returned to pretreatment baseline. For subsequent 
infusions, the dose should be reduced to 12 mg/kg for serious Grade 3 toxicities and to 10 mg/kg for 
Grade 4 toxicities. If a Grade 3 toxicity recurs despite the dose reduction, the dose should be reduced 
further to 10 mg/kg. In case of recurrence of a Grade 4 toxicity, treatment with olaratumab should be 
permanently discontinued. 
 
Neutropenia 

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If neutropenic fever/infection or Grade 4 neutropenia lasting longer than 1 week occurs, administration 
of olaratumab should be temporarily discontinued until the absolute neutrophil count is 1,000 / µL or 
higher and then the dose of olaratumab should be resumed at the reduced dose of 12 mg/kg. If 
neutropenic fever/infection or Grade 4 neutropenia lasting longer than 1 week recurs despite dose 
reduction, the dose should be reduced further to 10 mg/kg. 
 
Special populations 
 
Elderly (> 65 years) 
Data on very elderly patients (> 75 years) are very limited (see sections 4.8 and 5.1).  
No dose reductions other than those recommended for the general patient population are necessary. 
 
Renal impairment 
There have been no formal studies with olaratumab in patients with renal impairment. PopPK data 
suggest that no dose adjustments are required in patients with mild or moderate renal impairment. 
There are no data regarding olaratumab administration in patients with severe renal impairment 
(calculated creatinine clearance < 30 mL/min) (see section 5.2). 
 
Hepatic impairment 
There have been no formal studies with olaratumab in patients with hepatic impairment. PopPK data 
suggest that no dose adjustments are required in patients with mild hepatic impairment. There are very 
limited data regarding olaratumab administration in patients with moderate hepatic impairment. There 
are no data in patients with severe hepatic impairment (see section 5.2).  
  
Paediatric population 
The safety and efficacy of olaratumab in children aged 0 to 18 years of age have not yet been 
established. No data are available. 
 
Method of administration  
 
After dilution in sodium chloride 9 mg/mL (0.9 %) solution for injection, olaratumab is administered 
as an intravenous infusion over approximately 60 minutes. In order to accommodate larger infusion 
volumes that may be needed for patients requiring higher doses, the duration of infusion should be 
increased such that the maximum infusion rate of 25 mg/minute is not exceeded.  
 
For instructions on dilution of the medicinal product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Infusion-related reactions 
Infusion-related reactions (IRRs), including anaphylactic reactions, were reported in clinical trials with 
olaratumab. The majority of these reactions occurred during or following the first olaratumab infusion. 
Symptoms of IRRs included flushing, shortness of breath, bronchospasm, or fever/chills, and in some 
cases manifested as severe hypotension, anaphylactic shock, or fatal cardiac arrest. Severe IRRs such 
as anaphylactic reactions can occur despite the use of premedication. Patients should be monitored 
during the infusion for signs and symptoms of IRRs in a setting with available resuscitation 
equipment. For management and dose adjustments in patients who experience Grade 1 or 2 IRR 
during the infusion, see section 4.2. In patients who have experienced a previous Grade 1 or 2 IRR, 
premedication with diphenhydramine hydrochloride (intravenously), paracetamol, and dexamethasone 
is recommended. Olaratumab should be immediately and permanently discontinued in patients who 
experience Grade 3 or 4 IRR (see sections 4.2 and 4.8).  
  

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Neutropenia 
Patients receiving olaratumab and doxorubicin are at risk of neutropenia (see section 4.8). Neutrophil 
count should be checked prior to Olaratumab dosing on Day 1 and Day 8 of each cycle. Neutrophil 
count should be monitored during the treatment with olaratumab and doxorubicin and supportive care 
should be administered such as antibiotics or G-CSF as per local guidelines. For dosage adjustments 
related to neutropenia, refer to section 4.2.  
 
Haemorrhagic events 
Patients receiving olaratumab and doxorubicin are at risk of haemorrhagic events (see section 4.8). 
Platelet counts should be checked prior to olaratumab dosing on Day 1 and Day 8 of each cycle. 
Coagulation parameters should be monitored in patients with conditions predisposing to bleeding, 
such as anticoagulant use. In a study of olaratumab in combination with liposomal doxorubicin, there 
was one case of fatal intracranial haemorrhage in a patient who had experienced a fall while on 
treatment. 
 
Anthracycline pre-treated patients 
The risk of cardiac toxicity rises with increasing cumulative doses of anthracyclines, including 
doxorubicin. There are no data for the combination of olaratumab and doxorubicin in anthracycline 
pre-treated patients, including pre-treatment with doxorubicin (see section 4.1). 
 
Sodium restricted diet 
This medicinal product contains 22 mg sodium per each 19 mL vial and 57 mg sodium per each 
50 mL vial. To be taken into consideration by patients on a controlled sodium diet. 
 
Cardiac toxicity 
Doxorubicin can cause cardiotoxicity. The risk of toxicity rises with increasing cumulative doses and 
is higher in individuals with a history of cardiomyopathy, mediastinal irradiation or pre-existing 
cardiac disease. To minimise doxorubicin-related cardiotoxicity, the use of appropriate cardio-
protective measures (LVEF measurement, such as ECHO or MUGA scan, ECG monitoring, and/or 
use of cardioprotective agents) should be considered and planned in all patients before the start and 
throughout the treatment.  
 
Please refer to doxorubicin SmPC for recommendation on cardiac monitoring. 
 
In the phase 2 trial, patients in both treatment groups that received 5 or more cycles of doxorubicin 
received dexrazoxane prior to each dose of doxorubicin from cycle 5 onwards to minimize the risk of 
doxorubicin-related cardiotoxicity (see sections 4.8 and 5.1).  
  
Hepatic impairment 
As doxorubicin is rapidly metabolised and predominantly eliminated by the biliary system, the toxicity 
of doxorubicin is enhanced in patients with hepatic impairment. Refer to doxorubicin SmPC for 
appropriate monitoring of hepatic function and doxorubicin dose adjustments in patients with impaired 
liver function. 
  
4.5 Interaction with other medicinal products and other forms of interaction 
 
Olaratumab is a human monoclonal antibody. In a dedicated DDI study, no pharmacokinetic 
interactions were observed in patients between olaratumab and doxorubicin. 
 
No other formal DDI studies with olaratumab and medicinal products commonly used in cancer 
patients, including those with STS (e.g. antiemetics, analgesics, anti-diarrheal drugs, oral 
contraceptives, etc.), have been performed.  
 
As monoclonal antibodies are not metabolised by cytochrome P450 (CYP) enzymes or other drug 
metabolising enzymes, inhibition or induction of these enzymes by co-administered medicinal 

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products is not anticipated to affect the pharmacokinetics of olaratumab. Conversely, olaratumab is not 
anticipated to affect the pharmacokinetics of co-administered medicinal products. 
 
Administration of live or live-attenuated vaccines in patients immunocompromised by 
chemotherapeutic agents including doxorubicin may result in serious or fatal infections. Vaccination 
with a live vaccine should be avoided in patients receiving olaratumab in combination with 
doxorubicin. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/contraception in females 
Women of childbearing potential should be advised to avoid becoming pregnant while on olaratumab 
and should be informed of the potential hazard to the pregnancy and foetus. Women of childbearing 
potential should be advised to use effective contraception during treatment and for at least 3 months 
following the last dose of olaratumab.  
 
Pregnancy 
There are no or limited amount of data from the use of olaratumab in pregnant women. Reproductive 
and development toxicity study conducted with an anti-murine PDGFRα antibody in mice showed 
foetal malformations and skeletal alterations (see section 5.3).  
Based on its mechanism of action (see section 5.1), olaratumab has the potential to cause foetal harm. 
Olaratumab is not recommended during pregnancy and in women of childbearing potential not using 
contraception, unless the potential benefit justifies the potential risk to the foetus. 
  
Breast-feeding 
It is not known whether olaratumab is excreted in human milk. Human IgG is excreted in human milk, 
therefore breast-feeding is not recommended during treatment with olaratumab and for at least 
3 months following the last dose. 
 
Fertility 
There are no data on the effect of olaratumab on human fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Olaratumab may have minor influence on the ability to drive and use machines. Due to frequent 
occurrence of fatigue, patients should be advised to use caution when driving or operating machinery.  
 
4.8 Undesirable effects 
 
Summary of the safety profile  
 
Olaratumab-treated patients from Phase 2 study 
In the olaratumab plus doxorubicin arm, the most serious (Grade ≥3) adverse drug reactions (ADRs) 
observed were neutropenia (54.7 %) and musculoskeletal pain (7.8 %). 
 
The most frequently occurring ADRs were nausea, musculoskeletal pain, neutropenia and mucositis. 
 
The most frequent ADRs associated with permanent treatment discontinuation occurred in 3 (4.7 %) 
patients of which the most frequent were infusion-related reactions (3.1 %) and mucositis (1.6 %). 
 
Known toxicities reported for doxorubicin, observed in the combination of olaratumab and 
doxorubicin include fatigue, anaemia, thrombocytopenia and alopecia. Please refer to the doxorubicin 
SmPC for complete descriptions of all adverse events associated with doxorubicin treatment 
 

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Tabulated list of adverse reactions 
 
ADRs which were reported in patients with soft tissue sarcoma treated with olaratumab in combination 
with doxorubicin in the Phase 2 study are listed below in Table 2 in MedDRA body system organ class, 
frequency and grade of severity. The following convention has been used for classification of frequency: 
Very common (≥ 1/10) 
Common (≥ 1/100 to < 1/10) 
Uncommon (≥ 1/1,000 to < 1/100) 
Rare (≥ 1/10,000 to < 1/1,000) 
Very rare (< 1/10,000) 
 
Within each frequency grouping, ADRs are presented in order of decreasing seriousness. 
 
Table 2: Adverse reactions in patients receiving olaratumab plus doxorubicin for soft tissue 
sarcoma during the Phase 2 portion of a Phase 1b/2 study 
 

System organ class Adverse Reactiona Frequency overall Grade 3/4 frequency 
Blood and lymphatic 
system disorders 
 

Neutropenia Very Common Very Common 
Lymphopenia Very Common Common 

Nervous system 
disorders 

Headache Very Common None reported 

Gastrointestinal 
disorders 

Diarrhoea Very Common Common 
Mucositis Very Common Common 
Nausea Very Common Common 
Vomiting Very Common None reported 

Musculoskeletal and 
connective tissue 
disorders 

Musculoskeletal 
Painb 

Very Common Common 

General disorders and 
administrative site 
conditions 

Infusion-related 
Reactionsc 

Very Common Common 

a Refer to NCI CTCAE Criteria (Version 4.03) for each Grade of toxicity 
b Musculoskeletal pain includes arthralgia, back pain, bone pain, flank pain, groin pain, 

musculoskeletal chest pain, musculoskeletal pain, myalgia, muscle spasms, neck pain, and pain in 
extremity. 

c Infusion-related reactions includes anaphylactic reactions/anaphylactic shock. 
  
Description of selected ADRs 
 
Infusion-related reactions (IRRs) 
IRRs were reported in 12.5 % of patients and mainly present as chills, fever or dyspnoea. Severe IRRs, 
also including a fatal case (see section 4.4) were reported in 3.1 % of patients and mainly presented 
with shortness of breath, loss of consciousness and hypotension. All severe IRRs occurred during or 
immediately after the first administration of olaratumab. 
 
Neutropenia 
In the phase 2 trial, the incidence of neutropenia was 59.4 % (all Grades) and 54.7 % (Grade 3) in the 
olaratumab plus doxorubicin arm and 38.5 % (all Grades) and 33.8 % (Grade 3) in the doxorubicin 
alone arm. The rate of febrile neutropenia was 12.5 % in the olaratumab plus doxorubicin arm and 
13.8 % in the doxorubicin alone arm. For dose adjustments, refer to section 4.2 
 
Musculoskeletal pain 
In the phase 2 trial the incidence of Musculoskeletal pain was 64.1 % (all Grades)  and 7.8 % 
(Grade 3) in the olaratumab plus doxorubicin arm and 24.6 % (all Grades) and 1.5 % (Grade 3) in the 

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doxorubicin alone arm. In the majority of patients the pain was related to the patients’ underlying 
cancer or metastases or pre-existing or concomitant conditions. The majority of these events occurred 
in the first 4 cycles. The pain can last from few days to up to 200 days. In some patients there was a 
recurrence of pain .The pain did not worsen with time or during recurrence. 
 
Cardiac toxicity 
No clinically meaningful difference in doxorubicin-related cardiotoxicity was observed between the 
two treatment arms of the study. The rate of cardiac arrhythmias was similar in both arms (15.6 % in 
the Investigational Arm and 15.4 % in the Control Arm). The rate of treatment-emergent cardiac 
dysfunction was comparable between the two treatment arms (7.8 % in the Investigational Arm and 
6.2 % in the Control Arm).  
 
Haemorrhagic events 
In the phase 2 trial, the frequency of haemorrhagic events considered related to any study drug was 
3.1 % in either treatment arm. All of these events were Grade 1/2 and were confounded by multiple 
factors. Three Grade ≥3 events, including one fatal, have been reported across the clinical 
development programme of olaratumab (see section 4.4). 
 
Toxicity in the elderly 
There was a higher incidence of Grade ≥3 adverse reactions, adverse reactions leading to 
discontinuation and a higher rate of haematological toxicity in the elderly population compared to the 
overall study population (see section 4.2). The rates of discontinuation were comparable between 
treatment arms across all age groups. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There is no experience with Lartruvo overdose in human clinical trials. Lartruvo has been 
administered in a Phase 1 study up to 20 mg/kg on days 1 and 8 of a 21 day cycle without reaching a 
maximum tolerated dose. In case of overdose, use supportive therapy. There is no known antidote to 
Lartruvo overdose.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies, ATC code: L01XC27 
 
Mechanism of action 
Olaratumab is an antagonist of platelet derived growth factor receptor-α (PDGFR-α), expressed on 
tumour and stromal cells. Olaratumab is a targeted, recombinant, fully human immunoglobulin G 
subclass 1 (IgG1) monoclonal antibody that specifically binds PDGFR-α, blocking PDGF AA, -BB, 
and -CC binding and receptor activation. As a result, in vitro olaratumab inhibits PDGFR-α pathway 
signalling in tumour and stromal cells. In addition, in vivo olaratumab has been shown to disrupt the 
PDGFR-α pathway in tumour cells and inhibit tumour growth.  
 
Immunogenicity 
As with all therapeutic proteins, there is the potential for immunogenicity. 
 

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http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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Overall, a low incidence of both treatment emergent anti-drug antibodies and neutralising antibodies 
were detected in clinical trial samples.  
 
Clinical efficacy and safety 
 
The efficacy and safety of olaratumab was assessed in a Phase 1b/2, multi-centre study in 
anthracycline naïve patients with histologically or cytologically confirmed, advanced soft tissue 
sarcoma not amenable to receive surgery or radiotherapy with curative intent. Patients with 
gastrointestinal stromal tumours (GIST) or Kaposi sarcoma were not enrolled. The Phase 2 portion of 
the study was a randomised, open label study of olaratumab plus doxorubicin versus doxorubicin 
alone. A total of 133 patients were randomised, of whom 129 received at least one dose of study 
treatment (64 in the olaratumab plus doxorubicin arm and 65 in the doxorubicin arm). Patients were 
required to have histologically or cytologically confirmed, advanced soft tissue sarcoma and ECOG 
performance status of 0-2. Randomisation was stratified by PDGFR-α expression (positive versus 
negative), number of previous lines of treatment (0 versus 1 or more lines), histological tumour type 
(leiomyosarcoma, synovial sarcoma, and others) and ECOG performance status (0 or 1 versus 2). 
 
Patients were randomised in a 1:1 ratio to either olaratumab (15 mg/kg) on Day 1 and Day 8 plus 
doxorubicin (75 mg/m²) on Day 1 of each 21-day cycle for up to 8 cycles or doxorubicin (75 mg/m2) 
alone on Day 1 of each 21-day cycle, also for up to 8 cycles. Olaratumab and doxorubicin were 
administered by intravenous infusion. During Cycles 5 to 8 on both arms, dexrazoxane (dosed at a 
ratio of 10:1 to the administered dose of doxorubicin) could be administered on Day 1 of each cycle at 
the investigator’s discretion to reduce potential doxorubicin-related cardiotoxicity. All patients 
receiving more than 4 cycles of doxorubicin received dexrazoxane. Patients in the olaratumab plus 
doxorubicin arm could continue on olaratumab monotherapy until disease progression, unacceptable 
toxicity or any other reason for treatment discontinuation occurred.   
 
Demographics and baseline characteristics were quite similar between treatment arms in the phase 2 
portion of the clinical trial. The median age was 58 years with 42 patients ≥ 65 years of age. 86.4 % of 
the patients were Caucasian. More than 25 different soft tissue sarcoma subtypes were represented in 
this trial, the most frequent being leiomyosarcoma (38.4 %), undifferentiated pleomorphic sarcoma 
(18.1 %) and liposarcoma (17.3 %). Other subtypes were infrequently represented. Patients had 
received 0-4 previous lines of therapy for treatment of advanced disease but had not previously 
received treatment with anthracyclines. The number of patients receiving post-study systemic therapy 
was similar between arms. Ten patients in the olaratumab plus doxorubicin arm and 5 patients in the 
doxorubicin arm received post-study radiotherapy only. 3 patients in the olaratumab plus doxorubicin 
arm and 1 patient in the doxorubicin arm had post-study surgery only. 2 patients in the olaratumab 
plus doxorubicin arm and none in the doxorubicin arm received both post-study radiotherapy and 
surgery.  
   
The median cumulative dose of doxorubicin was 487.6 mg/m2 in the olaratumab plus doxorubicin arm 
and 299.6 mg/m2 in the doxorubicin alone arm. The primary efficacy outcome measure was 
progression free survival (PFS) by investigator assessment. Key secondary efficacy outcome measures 
were overall survival (OS) and objective response rate (ORR) (see Table 3). The study met its primary 
endpoint (PFS). PFS according to a post-hoc, blinded, independent assessment was 8.2 months vs 
4.4 months; HR = 0.670; p = 0.1208. A statistically significant improvement in OS was seen in the 
olaratumab plus doxorubicin arm in comparison to treatment with doxorubicin alone in the overall 
population. The main analysis was performed in the following two subgroups: Leiomyosarcoma 
(LMS) and non-LMS (other). Subgroups analysis of OS is shown in figure 2. Difference in objective 
response rate [complete response (CR) + partial response (PR)] according to investigator assessment 
was not statistically significant (18.2 % vs 11.9 % in patients randomised to olaratumab plus 
doxorubicin compared to patients randomized to doxorubicin respectively). 
 
Efficacy results are shown in Table 3 and Figures 1 and 2.  
 

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Table 3. Summary of survival data – ITT population 
 

 Lartruvo plus doxorubicin 
(n = 66) 

Doxorubicin alone 
(n = 67) 

Progression free survival, months* 
     Median (95 % CI) 6.6 (4.1, 8.3) 4.1 (2.8, 5.4) 
     Hazard ratio (95 % CI) 0.672 (0.442, 1.021) 
     p-value 0.0615** 
Overall survival, months 
     Median (95 % CI) 26.5 (20.9, 31.7) 14.7 (9.2, 17.1) 
     Hazard ratio (95 % CI) 0.463 (0.301, 0.710) 
     p-value 0.0003 

Abbreviations: CI = confidence interval 
* By investigator assessment 
**Met phase 2 protocol defined significance level of 0.19 
 
Figure 1. Kaplan-Meier curves of overall survival for Lartruvo plus doxorubicin versus 
doxorubicin alone 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
  

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Figure 2. Forest plot for subgroup analysis of overall survival (ITT population) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
olaratumab in one or more subsets of the paediatric population in soft tissue sarcoma (see section 4.2 
for information on paediatric use). 
 
This medicinal product has been authorised under a so-called ‘conditional approval’ scheme.  
This means that further evidence on this medicinal product is awaited. 
The European Medicines Agency will review new information on this medicinal product at least every 
year and this SmPC will be updated as necessary . 
 
5.2 Pharmacokinetic properties 
 
Absorption 
Olaratumab is administered as an intravenous infusion only. 
 
Distribution 
The population pharmacokinetic (PopPK) model-based mean (CV %) volume of distribution of 
olaratumab at steady state (Vss) was 7.7 L (16 %). 
 
Elimination 
The PopPK model-based mean (CV %) clearance for olaratumab was 0.56 L/day (33 %). This 
corresponds to a mean terminal half-life of approximately 11 days. 
 
Special populations 
Age, sex, and race had no clinically meaningful effect on the PK of olaratumab based on a PopPK 
analysis. Clearance and volume of distribution had a positive correlation with body weight. 
 

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Renal impairment 
No formal studies have been conducted to evaluate the effect of renal impairment on the PK of 
olaratumab. Based on a PopPK analysis, no clinically meaningful differences in the clearance of 
olaratumab were observed in patients with mild (calculated creatinine clearance [CLcr] 60-89 mL/min, 
n = 43), or moderate (CLcr 30-59 mL/min, n = 15) renal impairment compared to patients with normal 
renal function (CLcr ≥90 mL/min, n = 85). No data were available from patients with severe renal 
impairment (CLcr 15-29 mL/min). 
 
Hepatic impairment 
No formal studies have been conducted to evaluate the effect of hepatic impairment on the PK of 
olaratumab. Based on a PopPK analysis, no clinically meaningful differences in the clearance of 
olaratumab were observed in patients with mild (total bilirubin within upper limit of normal [ULN] 
and AST>ULN, or total bilirubin > 1.0-1.5 times ULN and any AST level, n = 16), or moderate (total 
bilirubin > 1.5-3.0 times ULN, n = 1) hepatic impairment compared to patients with normal hepatic 
function (total bilirubin and AST ≤ ULN, n = 126). No data were available from patients with severe 
hepatic impairment (total bilirubin > 3.0 times ULN and any AST level). 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on repeat dose toxicity studies in 
monkeys. 
 
No animal studies have been performed to test olaratumab for potential of carcinogenicity, 
genotoxicity, or fertility impairment. Administration of an anti-murine PDGFR- α surrogate antibody 
to pregnant mice during organogenesis at 50 and 150 mg/kg resulted in increased malformations 
(abnormal eyelid development) and skeletal alterations (frontal/parietal additional ossification site). 
The foetal effects in mice administered the surrogate antibody occurred at exposures less than the 
AUC exposure at the maximum recommended human dose of 15 mg/kg olaratumab. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol (E421) 
Glycine (E640) 
Sodium chloride 
L-Histidine monohydrochloride monohydrate 
L-Histidine 
Polysorbate 20 (E432) 
Water for injections 
  
6.2 Incompatibilities 
 
The medicinal product should not be administered or mixed with dextrose containing solutions. 
 
6.3 Shelf life 
 
Unopened vial 
2 years. 
 
After dilution 
This product is preservative free. From a microbiological point of view the prepared dosing solution 
should be used immediately. If not used immediately, the dosing solution should be stored under 
refrigeration for up to 24 hours at 2 °C to 8 °C and up to an additional 8 hours at room temperature (up 

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to 25 °C) assuming dilution has taken place in controlled and validated aseptic conditions. Storage 
times include the duration of infusion.  
  
6.4 Special precautions for storage 
 
Store in a refrigerator (2° C - 8° C). 
Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 
For storage conditions after dilution of the medicinal product, see section 6.3. 
  
6.5 Nature and contents of container  
 
19 mL solution in a vial (Type I glass) with a chlorobutyl elastomeric stopper, an aluminium seal and 
a polypropylene cap.   
50 mL solution in a vial (Type I glass) with a chlorobutyl elastomeric stopper, an aluminium seal and 
a polypropylene cap. 
 
Pack of 1 vial of 19 mL. 
Pack of 2 vials of 19 mL. 
Pack of 1 vial of 50 mL. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
The infusion solution should be prepared using aseptic technique to ensure the sterility of the prepared 
solution.  
 
Each vial is intended for single use only. Do not shake the vial. The content of the vials should be 
inspected for particulate matter and discolouration (the concentrate for solution for infusion should be 
clear to slightly opalescent and colourless to slightly yellow without visible particles) prior to 
administration. If particulate matter or discolouration is identified, the vial must be discarded. The 
dose and volume of olaratumab needed should be calculated to prepare the infusion solution. Vials 
contain 190 mg or 500 mg as a 10 mg/mL solution of olaratumab. Only use sodium chloride 
9 mg/mL (0.9 %) solution for injection as a diluent.  
 
In case of prefilled intravenous infusion container usage  
Based on the calculated volume of olaratumab, the corresponding volume of sodium chloride 
9 mg/mL (0.9 %) solution for injection should be removed from the prefilled 250 mL intravenous 
container. The calculated volume of olaratumab should be aseptically transferred to the intravenous 
container. The final total volume in the container should be 250 mL. The container should be gently 
inverted to ensure adequate mixing. DO NOT FREEZE OR SHAKE the infusion solution.   
 
In case of empty intravenous infusion container usage 
The calculated volume of olaratumab should be aseptically transferred into an empty intravenous 
infusion container. A sufficient quantity of sodium chloride 9 mg/mL (0.9 %) solution for injection 
should be added to the container to make the total volume 250 mL. The container should be gently 
inverted to ensure adequate mixing. DO NOT FREEZE OR SHAKE the infusion solution.  
 
Administer via an infusion pump. A separate infusion line must be used and the line must be flushed 
with sodium chloride 9 mg/mL (0.9 %) solution for injection at the end of the infusion. 
  
Any unused portion of olaratumab left in a vial should be discarded, as the product contains no 
antimicrobial preservatives.  
 

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Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V. 
Papendorpseweg 83 
3528 BJ Utrecht 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1143/001-003  
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 9 November 2016 
Date of latest renewal:  21 September 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

  

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15 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 

MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 

FOR THE CONDITIONAL MARKETING AUTHORISATION 
 

 

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A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer(s) of the biological active substance(s)  
ImClone Systems LLC 
33 ImClone Drive 
Branchburg 
New Jersey 
NJ 08876 
UNITED STATES 
 
Name and address of the manufacturer(s) responsible for batch release 
Lilly S.A. 
Avda. de la Industria  30 
Alcobendas 
28108 Madrid 
SPAIN 

 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 

• Periodic safety update reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
The marketing authorisation holder shall submit the first periodic safety update report for this 
product within 6 months following authorisation.  
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

• Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the  
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

 
• Additional risk minimisation measures   

 
Not applicable. 

 

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E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 
FOR THE CONDITIONAL MARKETING AUTHORISATION  

 
This being a conditional marketing authorisation and pursuant to Article 14(7) of Regulation (EC) 
No 726/2004, the MAH shall complete, within the stated timeframe, the following measures: 
 

Description Due date 
In order to further confirm the efficacy and safety of olaratumab in the 
treatment of patients with advanced soft tissue sarcoma, the MAH should 
submit the clinical study report of the phase III study JGDJ comparing 
doxorubicin plus olaratumab versus doxorubicin in patients with 
advanced or metastatic STS (including exploratory biomarker data).  
 

 31 January 2020 
 
 
 
 

 
 
  

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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  

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A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON – 50 mL vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Lartruvo 10 mg/mL concentrate for solution for infusion  
olaratumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One mL of concentrate contains 10 mg of olaratumab. 
One vial of 50 mL contains 500 mg olaratumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, glycine, sodium chloride, L-histidine monohydrochloride monohydrate, 
L-histidine, polysorbate 20 and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
 
500 mg/50 mL 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after dilution. 
For single use only.  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
  
Do not shake.  
 
 
8. EXPIRY DATE 
 
EXP 
 

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9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze.  
Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V. 
Papendorpseweg 83,  
3528 BJ Utrecht 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1143/001  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 

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NN: 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON – 19 mL vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Lartruvo 10 mg/mL concentrate for solution for infusion  
olaratumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One mL of concentrate contains 10 mg of olaratumab. 
One vial of 19 mL contains 190 mg olaratumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, glycine, sodium chloride, L-histidine monohydrochloride monohydrate, 
L-histidine, polysorbate 20 and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
 
190 mg/19 mL 
1 vial 
2 vials 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after dilution. 
For single use only.  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
  
Do not shake.  
 
 
8. EXPIRY DATE 
 
EXP 

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9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze.  
Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V. 
Papendorpseweg 83,  
3528 BJ Utrecht 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1143/002 – 1 vial of 19 mL. 
EU/1/16/1143/003 – 2 vials of 19 mL. 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 

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PC: 
SN: 
NN: 
  

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PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
VIAL LABEL – 50 mL vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Lartruvo 10 mg/mL sterile concentrate 
olaratumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One mL of concentrate contains 10 mg of olaratumab. 
One vial of 50 mL contains 500 mg olaratumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, glycine, sodium chloride, L-histidine monohydrochloride monohydrate, 
L-histidine, polysorbate 20 and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
 
500 mg/50 mL 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For IV use after dilution. 
For single use only.  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
  
Do not shake.  
 
 
8. EXPIRY DATE 
 
EXP 

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9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze.  
Keep the vial in the outer carton. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V. 
Papendorpseweg 83,  
3528 BJ Utrecht 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1143/001  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
  

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PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
VIAL LABEL – 19 mL vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Lartruvo 10 mg/mL sterile concentrate 
olaratumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One mL of concentrate contains 10 mg of olaratumab. 
One vial of 19 mL contains 190 mg olaratumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, glycine, sodium chloride, L-histidine monohydrochloride monohydrate, 
L-histidine, polysorbate 20 and water for injections. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
 
190 mg/19 mL 
1 vial 
2 vials 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For IV use after dilution. 
For single use only.  
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
  
Do not shake.  
 
 
8. EXPIRY DATE 
 
EXP 

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9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze.  
Keep the vial in the outer carton. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Eli Lilly Nederland B.V. 
Papendorpseweg 83,  
3528 BJ Utrecht 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1143/002 – 1 vial of 19 mL. 
EU/1/16/1143/003 – 2 vials of 19 mL. 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
  

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B. PACKAGE LEAFLET 

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Package leaflet: Information for the user 
 

Lartruvo 10 mg/mL concentrate for solution for infusion 
olaratumab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you are given this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor. 
- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 

in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Lartruvo is and what it is used for  
2. What you need to know before you are given Lartruvo 
3. How you are given Lartruvo 
4. Possible side effects  
5. How to store Lartruvo  
6. Contents of the pack and other information 
 
 
1. What Lartruvo is and what it is used for 
 
Lartruvo contains the active substance olaratumab, which belongs to a group of medicines called 
monoclonal antibodies. 
 
Olaratumab recognises and attaches specifically to a protein known as platelet-derived growth factor 
receptor-α (PDGFR-α). PDGFR-α is found in large amounts on some cancer cells where it stimulates 
the cells to grow and divide. When olaratumab attaches to PDGFR-α it may prevent cancer cell growth 
and survival. 
 
Lartruvo is used in combination with another anti-cancer medicine called doxorubicin for the 
treatment of adults with advanced soft tissue sarcoma who have not been previously treated with 
doxorubicin. Soft tissue sarcoma is a cancer that starts in the soft tissues, such as the muscles, fat, 
cartilage and blood vessels. 
 
 
2. What you need to know before you are given Lartruvo 
 
You must not be given Lartruvo 
- if you are allergic to olaratumab or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions  
You should tell your doctor about any of the following:  
-  if you are receiving any treatment for heart disease or liver disease 
 
Talk to your doctor or nurse immediately if the following applies to you (or you are not sure): 
 

– Infusion-related reaction 
Infusion-related reactions may occur during treatment with Lartruvo. Such reactions may be allergic. 
Symptoms may include back pain, chest pain and/or tightness, chills, fever, flushing, difficulty in 

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breathing and wheezing. In severe cases, you may experience very low blood pressure, feel faint, and 
experience breathing distress caused by narrowing of the airways, which could be life-threatening. 
Your doctor will give you other medicines before you receive Lartruvo to reduce the risk of infusion-
related reactions. Your doctor or nurse will check for side effects during and after your infusion. If you 
have a severe infusion-related reaction, your doctor may recommend reducing the dose of Lartruvo or 
stop your treatment with Lartruvo. See section 4 for more details about infusion-related reactions 
which may occur during or after the infusion.  
  

– Bleeding 
Lartruvo and doxorubicin may decrease your platelet count. Platelets help your blood to clot and a low 
platelet count may increase the risk of bleeding. If you experience significant bleeding, symptoms may 
include extreme tiredness, weakness, dizziness or changes in the colour of your stools. Your doctor 
will check your platelet count prior to treatment with Lartruvo. 
 

– Reduction in the number of white blood cells 
Lartruvo and doxorubicin may decrease the number of white blood cells (including neutrophils). 
White blood cells are important for fighting infection. A low white blood cell count may increase your 
risk for infection. Your doctor will check your white blood cell counts prior to treatment with 
Lartruvo. 
 
Children and adolescents 
Lartruvo should not be given to patients under the age of 18 years because there is no information 
about how it works in this age group. 
 
Other medicines and Lartruvo 
Tell your doctor if you are taking, have recently taken or might take any other medicines.  
 
Pregnancy and breast-feeding 
Before starting treatment you must tell your doctor if you are pregnant or breast-feeding, think you 
may be pregnant or are planning to have a baby. 
 
Avoid getting pregnant while receiving this medicine and for at least 3 months after the last dose of 
Lartruvo as this medicine may harm your unborn child. Talk to your doctor about the best 
contraception for you. 
 
It is not known whether olaratumab gets into breast milk and if the breast-fed infant is at risk of harm. 
Ask your doctor if you can breast-feed during or after treatment with Lartruvo.  
 
Driving and using machines 
It is not known if Lartruvo will affect your ability to drive. If you get any symptoms that affect your 
ability to concentrate and react, such as tiredness, do not drive or use machines until the effect goes 
away. 
 
Lartruvo contains sodium 
This medicine contains 22 mg sodium in each 19 mL vial and 57 mg sodium in each 50 mL vial. This 
should be taken into consideration if you are on a controlled sodium diet. 
  
 
3. How you are given Lartruvo 
 
A doctor experienced in the use of anti-cancer medicines will supervise your Lartruvo therapy. 
 
Premedication 
You will be given medicines to reduce the risk of an infusion-related reaction before you receive 
Lartruvo. 
 

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Dose and administration 
The recommended dose of Lartruvo is 15 mg per kilogram of your body weight on days 1 and 8 of 
each 3-week cycle. Lartruvo is given in combination with the medicine doxorubicin for up to 8 cycles 
and then it is given on its own. The number of infusions that you receive will depend on how well and 
for how long treatment with Lartruvo works and how well you feel. Your doctor will discuss this with 
you. 
 
This medicine is given as an infusion into a vein via a drip. The drip lasts about 60 minutes. 
 
Detailed instructions for your doctor or your nurse on how to prepare Lartruvo infusion are included at 
the end of this package leaflet (see ‘Handling instructions’). 
 
Dose adjustments 
During each infusion, your doctor or nurse will check for side effects. Your doctor may also give you 
a smaller dose or delay your dose of Lartruvo if you get serious side effects including a lowering of 
your white blood cell counts. If you have an infusion-related reaction during treatment, your doctor or 
nurse may slow down or stop your Lartruvo infusion. 
  
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Your 
doctor will discuss these with you and will explain the risks and benefits of your treatment. 
 
The following side effects have been reported: 
 
Infusion reactions 
Lartruvo has been associated with infusion reactions (see section 2 “Warnings and precautions”). Tell 
your doctor or nurse immediately if you feel unwell during infusion. Below is a list of some typical 
symptoms associated with infusion reactions: 

• Feeling faint 
• Fever 
• Chills 
• Flushing 
• Shortness of breath 

 
Other symptoms may occur as well (see section 2 “Warnings and precautions”). Your doctor may 
consider slowing the Lartruvo infusion or interrupting it to manage these symptoms. 
 
Very common (may affect more than 1 in 10 people): 

– nausea 
– pain in your muscles, joints or bones (musculoskeletal pain) 
– low white blood cell counts (including neutrophils and lymphocytes which may increase the 

risk of infection) 
– pain or sores in your mouth or throat (mucositis) 
– vomiting  
– diarrhoea 
– headache 
– infusion-related reactions 

 
Reporting of side effects 
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 
leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 
By reporting side effects you can help provide more information on the safety of this medicine. 
 
 

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34 

5. How to store Lartruvo 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the outer carton and vial label after 
EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2 °C – 8 °C). 
Do not freeze or shake the vial. 
Keep the vial in the outer carton to protect from light. 
 
Infusion solution: After dilution and preparation, the medicine must be used immediately. If not used 
immediately, in-use storage times and conditions before use are the responsibility of the user and 
would normally not be longer than 24 hours at 2 to 8 ºC and up to an additional 8 hours at room 
temperature (below 25 ºC). Do not freeze or shake the infusion solution. Do not administer the 
solution if you notice any particulate matter or discoloration. 
 
This medicine is for single use only.  
 
Do not store any unused portion of the infusion solution for reuse. Any unused medicine or waste 
material should be disposed of in accordance with local requirements.  
 
 
6. Contents of the pack and other information 
 
What Lartruvo contains  
- The active substance is olaratumab. Each millilitre of the concentrate for solution for infusion 

contains 10 mg of olaratumab. 
Each 19 mL vial contains 190 mg of olaratumab. 
Each 50 mL vial contains 500 mg of olaratumab. 

- The other ingredients are mannitol, glycine, L-histidine monohydrochloride monohydrate, 
L-histidine, sodium chloride (see section 2 “Lartruvo contains sodium”), polysorbate 20 and 
water for injections.  

 
What Lartruvo looks like and contents of the pack 
Lartruvo concentrate for solution for infusion (sterile concentrate) is a clear to slightly opalescent and 
colourless to slightly yellow liquid supplied in a glass vial with an elastomeric stopper. 
 
It is available in packs of:  
- 1 vial of 19 mL 
- 2 vials of 19 mL 
- 1 vial of 50 mL 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
Eli Lilly Nederland B.V. 
Papendorpseweg 83 
3528 BJ Utrecht 
The Netherlands. 
 
Manufacturer  
Lilly S.A. 
Avda de la Industria, 30 
28108 Alcobendas 
Madrid 
Spain 

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35 

 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Eli Lilly Benelux S.A./N.V. 
Tél/Tel: + 32-(0)2 548 84 84 

Lietuva 
Eli Lilly Holdings Limited atstovybė 
Tel. +370 (5) 2649600 

България 
ТП "Ели Лили Недерланд" Б.В. - България 
тел. + 359 2 491 41 40 

Luxembourg/Luxemburg 
Eli Lilly Benelux S.A./N.V. 
Tél/Tel: + 32-(0)2 548 84 84 

Česká republika 
ELI LILLY ČR, s.r.o. 
Tel: + 420 234 664 111 

Magyarország 
Lilly Hungária Kft. 
Tel: + 36 1 328 5100 

Danmark 
Eli Lilly Danmark A/S  
Tlf: +45 45 26 60 00 

Malta 
Charles de Giorgio Ltd. 
Tel: + 356 25600 500 

Deutschland 
Lilly Deutschland GmbH 
Tel. + 49-(0) 6172 273 2222 

Nederland 
Eli Lilly Nederland B.V.  
Tel: + 31-(0) 30 60 25 800 

Eesti 
Eli Lilly Holdings Limited Eesti filiaal  
Tel: +372 6 817 280 

Norge 
Eli Lilly Norge A.S.  
Tlf: + 47 22 88 18 00 

Ελλάδα 
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε.  
Τηλ: +30 210 629 4600 

Österreich 
Eli Lilly Ges.m.b.H.  
Tel: + 43-(0) 1 711 780 

España 
Lilly S.A. 
Tel: + 34-91 663 50 00 

Polska 
Eli Lilly Polska Sp. z o.o. 
Tel: +48 22 440 33 00 

France 
Lilly France SAS 
Tél: +33-(0) 1 55 49 34 34 

Portugal 
Lilly Portugal Produtos Farmacêuticos, Lda 
Tel: + 351-21-4126600 

Hrvatska 
Eli Lilly Hrvatska d.o.o. 
Tel: +385 1 2350 999 

România 
Eli Lilly România S.R.L. 
Tel: + 40 21 4023000 

Ireland 
Eli Lilly and Company (Ireland) Limited 
Tel: + 353-(0) 1 661 4377 

Slovenija 
Eli Lilly farmacevtska družba, d.o.o. 
Tel: +386 (0)1 580 00 10 

Ísland 
Icepharma hf. 
Sími + 354 540 8000 

Slovenská republika 
Eli Lilly Slovakia, s.r.o. 
Tel: + 421 220 663 111 

Italia 
Eli Lilly Italia S.p.A. 
Tel: + 39- 055 42571 

Suomi/Finland 
Oy Eli Lilly Finland Ab  
Puh/Tel: + 358-(0) 9 85 45 250 

Κύπρος 
Phadisco Ltd  
Τηλ: +357 22 715000 

Sverige 
Eli Lilly Sweden AB 
Tel: + 46-(0) 8 7378800 

Latvija 
Eli Lilly Holdings Limited pārstāvniecība Latvijā 
Tel: +371 67364000 

United Kingdom 
Eli Lilly and Company Limited 
Tel: + 44-(0) 1256 315000 

 
This leaflet was last revised in < {month YYYY}>. 
 
This medicine has been given ‘conditional approval’. This means that there is more evidence to come 
about this medicine. 
The European Medicines Agency will review new information on this medicine at least every year and 
this leaflet will be updated as necessary. 
  

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36 

Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  

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http://www.ema.europa.eu/


37 

--------------------------------------------------------------------------------------------------------------------------- 
Handling instructions 
Lartruvo 10 mg/mL 

concentrate for solution for infusion 
olaratumab 

 
The following information is intended for healthcare professionals only 
 
Prepare the infusion solution using aseptic technique to ensure the sterility of the prepared solution. 
 
Each vial is intended for single use only. Inspect the contents of the vials for particulate matter and 
discolouration. The concentrate for solution for infusion must be clear to slightly opalescent and 
colourless to slightly yellow prior to dilution. If particulate matter or discolouration is identified, the 
vial must be discarded.  
 
Vials contain 190 mg or 500 mg as a 10 mg/mL solution of olaratumab; calculate the dose and volume 
of olaratumab needed to prepare the infusion solution. Only use sodium chloride 9 mg/mL (0.9 %) 
solution for injection as a diluent. 
 
To administer using pre-filled intravenous infusion containers   
Based on the calculated volume of olaratumab, aseptically remove the corresponding volume of 
sodium chloride 9 mg/mL (0.9 %) solution for injection from the prefilled 250 mL intravenous 
container and transfer the olaratumab medicine into the container to bring the final volume in the 
container back to 250 mL. Gently invert the container to mix. DO NOT FREEZE OR SHAKE the 
infusion solution. DO NOT dilute with other solutions or co-infuse with other electrolytes or 
medicines. 
 
To administer using empty intravenous infusion containers 
Aseptically transfer the calculated volume of olaratumab into an empty intravenous infusion container. 
Add a sufficient quantity of sodium chloride 9 mg/mL (0.9 %) solution for injection to the container to 
make the total volume 250 mL. Gently invert the container to mix. DO NOT FREEZE OR SHAKE 
the infusion solution. DO NOT dilute with other solutions or co-infuse with other electrolytes or 
medicines. 
 
Administer via an infusion pump. A separate infusion line must be used and the line must be flushed 
with sodium chloride 9 mg/mL (0.9 %) solution for injection at the end of the infusion. 
 
Parenteral medicines should be inspected visually for particulate matter prior to administration. If 
particulate matter is identified, discard the infusion solution. 
 
Discard any unused portion of olaratumab left in a vial, as the product contains no antimicrobial 
preservatives. 
 
Any unused medicines or waste material should be disposed of in accordance with local requirements. 
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38 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Annex IV 
 

Scientific conclusions and grounds for the variation to the terms of the marketing 
authorisation(s) 

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39 

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for olaratumab, the scientific 
conclusions of CHMP are as follows: 
 
Based on cases of anaphylactic reaction and anaphylactic shock reported in the post-marketing setting, 
these adverse drug reactions should be specifically be mentioned under the category of 
infusion-related reactions in section 4.8 of the SmPC. The frequency of anaphylactic 
reactions/anaphylactic shock is already calculated as part of grade 3-4 infusion-related reactions in the 
table of Adverse Drug Reactions (ADRs) in the same section of the SmPC. The current wording of the 
Package leaflet is considered sufficient to communicate this risk. 
 
The CHMP agrees with the scientific conclusions made by the PRAC. 
 
Grounds for the variation to the terms of the marketing authorisation(s) 
 
On the basis of the scientific conclusions for olaratumab the CHMP is of the opinion that the benefit-
risk balance of the medicinal product(s) containing olaratumab is unchanged subject to the proposed 
changes to the product information. 
 
The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 
 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE CONDITIONAL MARKETING AUTHORISATION 
	A. LABELLING
	B. PACKAGE LEAFLET
	Scientific conclusions and grounds for the variation to the terms of the marketing authorisation(s)