IMFINZI Concentrate for solution for infusion Ref.[8680] Active ingredients: Durvalumab

Treatment must be initiated and supervised by a physician experienced in the treatment of cancer.

PD-L1 testing for patients with locally advanced NSCLC

Patients with locally advanced NSCLC should be evaluated for treatment based on the tumour expression of PD-L1 confirmed by a validated test (section 5.1).

MMR testing for patients with endometrial cancer

Patients with endometrial cancer should be evaluated for treatment based on tumour MMR status confirmed by a validated test (see section 5.1).

Posology

The recommended dose for IMFINZI monotherapy and IMFINZI combination therapy is presented in Table 1. IMFINZI is administered as an intravenous infusion over 1 hour.

When IMFINZI is administered in combination with other therapeutic agents, refer to the summary of product characteristics (SmPC) of the therapeutic agents for further information.

Table 1. Recommended dose of IMFINZI monotherapy and combination therapy:

^a Patients with a body weight of 30 kg or less must receive weight-based dosing, equivalent to IMFINZI 10 mg/kg every 2 weeks or 20 mg/kg every 4 weeks as monotherapy until weight increases to greater than 30 kg.
^b It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed.
^c Metastatic NSCLC patients with a body weight of 30 kg or less must receive weight-based dosing, equivalent to IMFINZI 20 mg/kg until weight is greater than 30 kg. Patients with a body weight of 34 kg or less must receive weight based dosing equivalent to tremelimumab 1 mg/kg until weight is greater than 34 kg.
^d Consider maintenance administration of pemetrexed for patients with non-squamous tumours who received treatment with pemetrexed and carboplatin/cisplatin during the platinum-based chemotherapy stage.
^e In the case of dose delay(s), a fifth dose of tremelimumab can be given after Week 16, alongside IMFINZI.
^f If patients receive fewer than 4 cycles of platinum-based chemotherapy, the remaining cycles of tremelimumab (up to a total of 5) alongside IMFINZI should be given during the post-platinum chemotherapy phase.
^g ES-SCLC patients with a body weight of 30 kg or less must receive weight-based dosing of IMFINZI at 20 mg/kg. In combination with chemotherapy dose every 3 weeks (21 days), followed by 20 mg/kg every 4 weeks as monotherapy until weight increases to greater than 30 kg.
^h BTC patients with a body weight of 36 kg or less must receive weight-based dosing of IMFINZI at 20 mg/kg. In combination with chemotherapy dose every 3 weeks (21 days), followed by 20 mg/kg every 4 weeks as monotherapy until weight increases to greater than 36 kg.
ⁱ HCC patients with a body weight of 30 kg or less must receive weight-based dosing, equivalent to IMFINZI 20 mg/kg until weight is greater than 30 kg. Patients with a body weight of 40 kg or less must receive weight-based dosing, equivalent to tremelimumab 4 mg/kg until weight is greater than 40 kg.
^j Endometrial cancer patients with a body weight of 30 kg or less during maintenance phase must receive weight-based dosing equivalent to IMFINZI at 20 mg/kg, until weight is greater than 30 kg.

Dose escalation or reduction is not recommended. Treatment withholding or discontinuation may be required based on individual safety and tolerability, see Table 2.

Guidelines for management of immune-mediated and non-immune-mediated adverse reactions are described in Table 2 (refer to section 4.4 for further management recommendations, monitoring and evaluation information).

Table 2. Treatment modifications for IMFINZI or IMFINZI in combination with other products:

^a Common Terminology Criteria for Adverse Events, version 4.03. ALT: alanine aminotransferase; AST: aspartate aminotransferase; ULN: upper limit of normal; BLV: baseline value.
^b For patients with alternative cause follow the recommendations for AST or ALT increases without concurrent bilirubin elevations.
^c If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue durvalumab based on recommendations for hepatitis with no liver involvement.
^d Adverse drug reaction is only associated with IMFINZI in combination with tremelimumab.
^e Permanently discontinue trememlimumab for Grade 3; however, treatment with durvalumab can be resumed once event has resolved.
^f Permanently discontinue IMFINZI if adverse reaction does not resolve to ≤ Grade 1 within 30 days or if there are signs of respiratory insufficiency.
^g With the exception of Grade 4 laboratory abnormalities, about which the decision to discontinue should be based on accompanying clinical signs/symptoms and clinical judgment.
^h Includes immune thrombocytopenia, pancreatitis, immune-mediated arthritis, uveitis and cystitis noninfective.
ⁱ Adverse drug reaction is only associated when olaparib maintenance treatment is used in combination with IMFINZI, following treatment with IMFINZI in combination with platinum-based chemotherapy.

Based on the severity of the adverse reaction, IMFINZI and/or tremelimumab should be withheld and corticosteroids administered (refer to section 4.4). After withhold, IMFINZI and/or tremelimumab can be resumed within 12 weeks if the adverse reactions improved to ≤ Grade 1 and the corticosteroid dose has been reduced to ≤10 mg prednisone or equivalent per day. IMFINZI and tremelimumab should be permanently discontinued for recurrent Grade 3 (severe) immune-mediated adverse reactions and for any Grade 4 (life-threatening) immune-mediated adverse reactions, except for endocrinopathies that are controlled with replacement hormones.

Special populations

Elderly

No dose adjustment is required for elderly patients (≥ 65 years of age) (see section 5.1).

Renal impairment

No dose adjustment of IMFINZI is recommended in patients with mild or moderate renal impairment. Data from patients with severe renal impairment are too limited to draw conclusions on this population (see section 5.2).

Hepatic impairment

No dose adjustment of IMFINZI is recommended for patients with mild or moderate hepatic impairment. Data from patients with severe hepatic impairment are too limited to draw conclusions on this population (see section 5.2).

Paediatric population

The safety and efficacy of IMFINZI in children and adolescents aged below 18 years of age has not been established with regard to NSCLC, SCLC, BTC and HCC. No data are available. Outside its authorised indications, IMFINZI in combination with tremelimumab has been studied in children aged 1 to 17 years with neuroblastoma, solid tumour and sarcoma, however the results of the study did not allow to conclude that the benefits of such use outweigh the risks. Currently available data are described in sections 5.1 and 5.2.

Method of administration

IMFINZI is for intravenous use. It is to be administered as an intravenous infusion solution over 1 hour (see section 6.6).

For instructions on dilution of the medicinal product before administration, see section 6.6.

IMFINZI in combination with chemotherapy

For NSCLC, ES-SCLC and BTC, when IMFINZI is administered in combination with chemotherapy, administer IMFINZI prior to chemotherapy on the same day.

IMFINZI in combination with tremelimumab and platinum-based chemotherapy

When IMFINZI is administered in combination with tremelimumab and platinum-based chemotherapy, tremelimumab is given first, followed by IMFINZI and then platinum-based chemotherapy on the same day of dosing.

When IMFINZI is administered in combination with a fifth dose of tremelimumab and pemetrexed maintenance therapy at week 16, tremelimumab is given first, followed by IMFINZI and then pemetrexed maintenance therapy on the same day of dosing.

IMFINZI, tremelimumab, and platinum-based chemotherapy are administered as separate intravenous infusions. IMFINZI and tremelimumab are each given over 1 hour. For platinum-based chemotherapy, refer to the SmPC for administration information. For pemetrexed maintenance therapy, refer to the SmPC for administration information. Separate infusion bags and filters for each infusion should be used.

During cycle 1, tremelimumab is to be followed by IMFINZI starting approximately 1 hour (maximum 2 hours) after the end of the tremelimumab infusion. Platinum-based chemotherapy infusion should start approximately 1 hour (maximum 2 hours) after the end of the IMFINZI infusion. If there are no clinically significant concerns during cycle 1, then at the physician’s discretion, subsequent cycles of IMFINZI can be given immediately after tremelimumab and the time period between the end of the IMFINZI infusion and the start of chemotherapy can be reduced to 30 minutes.

IMFINZI in combination with tremelimumab

For uHCC, when IMFINZI is administered in combination with tremelimumab, administer tremelimumab prior to IMFINZI on the same day. IMFINZI and tremelimumab are administered as separate intravenous infusions. Refer to the SmPC for tremelimumab dosing information.

There is no information on overdose with durvalumab. In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted immediately.

Unopened vial:

3 years.

Diluted solution:

Chemical and physical in-use stability has been demonstrated for up to 30 days at 2°C to 8°C and for up to 24 hours at room temperature (up to 25°C) from the time of preparation.

From a microbiological point of view, the prepared solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C or 12 hours at room temperature (up to 25°C), unless dilution has taken place in controlled and validated aseptic conditions.

Store in a refrigerator (2°C–8°C).

Do not freeze.

Store in the original package in order to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

Two pack sizes of IMFINZI are available:

2.4 ml (a total of 120 mg durvalumab) of concentrate in a Type 1 glass vial with an elastomeric stopper and a gray flip-off aluminium seal. Pack size of 1 vial.

10 ml (a total of 500 mg durvalumab) of concentrate in a Type 1 glass vial with an elastomeric stopper and a white flip-off aluminium seal. Pack size of 1 vial.

Not all pack sizes may be marketed.

Preparation of solution:

IMFINZI is supplied as a single-dose vial and does not contain any preservatives, aseptic technique must be observed.

• Visually inspect the medicinal product for particulate matter and discolouration. IMFINZI is clear to opalescent, colourless to slightly yellow solution. Discard the vial if the solution is cloudy, discoloured or visible particles are observed. Do not shake the vial.
• Withdraw the required volume from the vial(s) of IMFINZI and transfer into an intravenous (IV) bag containing sodium chloride 9 mg/ml (0.9%) solution for injection, or glucose 50 mg/ml (5%) solution for injection. Mix diluted solution by gentle inversion. The final concentration of the diluted solution should be between 1 mg/ml and 15 mg/ml. Do not freeze or shake the solution.
• Discard any unused portion left in the vial.

Administration:

• Administer the infusion solution intravenously over 1 hour through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.
• Do not co-administer other medicinal products through the same infusion line. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.