Drug Detail:Imfinzi (Durvalumab [ dur-val-ue-mab ])
Generic Name: DURVALUMAB 120mg in 2.4mL
Dosage Form: injection, solution
Drug Class: Anti-PD-1 and PD-L1 monoclonal antibodies (immune checkpoint inhibitors)
Recommended Dosage
The recommended dosages for IMFINZI as a single agent and IMFINZI in combination with other therapeutic agents are presented in Table 1, 2 and 3.
Administer IMFINZI as an intravenous infusion after dilution as recommended [see Dosage and Administration (2.3)].
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Indication |
Recommended IMFINZI dosage |
Duration of Therapy |
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Single Agent |
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Unresectable stage III NSCLC |
Patients with a body weight of ≥ 30 kg: 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks Patients with a body weight of < 30 kg: 10 mg/kg every 2 weeks |
Until disease progression, unacceptable toxicity, or a maximum of 12 months |
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Combination with Other Therapeutic Agents |
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ES-SCLC |
Patients with a body weight of ≥ 30 kg: 1,500 mg in combination with chemotherapy* every 3 weeks (21 days) for 4 cycles, followed by 1,500 mg every 4 weeks as a single agent Patients with a body weight of < 30 kg: 20 mg/kg in combination with chemotherapy* every 3 weeks (21 days) for 4 cycles, followed by 10 mg/kg every 2 weeks as a single agent |
Until disease progression or unacceptable toxicity |
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BTC |
Patients with a body weight of ≥ 30 kg: 1,500 mg in combination with chemotherapy* every 3 weeks (21 days) up to 8 cycles followed by 1,500 mg every 4 weeks as a single agent Patients with a body weight of < 30 kg: 20 mg/kg in combination with chemotherapy* every 3 weeks (21 days) up to 8 cycles followed by 20 mg/kg every 4 weeks as a single agent |
Until disease progression or until unacceptable toxicity |
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uHCC |
Patients with a body weight of 30 kg and more:
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After Cycle 1 of combination therapy, administer IMFINZI as a single agent every 4 weeks until disease progression or unacceptable toxicity |
IMFINZI in Combination with Tremelimumab-actl and Platinum-Based Chemotherapy
The recommended dosage schedule and regimens for IMFINZI for the treatment of metastatic non-small cell lung cancer (NSCLC) are provided in Tables 2 and 3.
Weigh patients prior to each infusion.
Calculate the appropriate dose using Table 3 below based on the patient’s weight and tumor histology.
| Week*,† | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | 24 | |
| Cycle: | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | |||||||||||||||||
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IMFINZI*,‡ |
X |
X |
X |
X |
X |
X |
X |
X |
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Tremelimumab-actl‡,§ |
X |
X |
X |
X |
X |
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Chemotherapy |
X |
X |
X |
X |
X¶ |
X¶ |
X¶ |
XÞ |
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| Tumor Histology | Patient Weight | IMFINZI Dosage | Tremelimumab-actl Dosage* | Platinum-based Chemotherapy Regimen* |
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Non-Squamous |
≥30kg |
1,500 mg |
75 mg |
OR
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<30kg |
20 mg/kg |
1 mg/kg |
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Squamous |
≥30kg |
1,500 mg |
75 mg |
OR
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<30kg |
20 mg/kg |
1 mg/kg |
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Dosage Modifications for Adverse Reactions
No dose reduction for IMFINZI is recommended. In general, withhold IMFINZI for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue IMFINZI for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating corticosteroids.
Dosage modifications for IMFINZI or IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy for adverse reactions that require management different from these general guidelines are summarized in Table 4.
| Adverse Reaction | Severity* | Dosage Modification |
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Grade 2 |
Withhold† |
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Grade 3 or 4 |
Permanently discontinue |
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Grade 2 |
Withhold† |
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Grade 3 |
Withhold† or permanently discontinue‡ |
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Grade 4 |
Permanently discontinue |
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Any grade |
Permanently discontinue |
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ALT or AST increases to more than 3 and up to 8 times the ULN or total bilirubin increases to more than 1.5 and up to 3 times ULN |
Withhold† |
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ALT or AST increases to more than 8 times ULN or total bilirubin increases to more than 3 times the ULN |
Permanently discontinue |
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AST or ALT is more than 1 and up to 3 times ULN at baseline and increases to more than 5 and up to 10 times ULN or AST or ALT is more than 3 and up to 5 times ULN at baseline and increases to more than 8 and up to 10 times ULN |
Withhold† |
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AST or ALT increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN |
Permanently discontinue |
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Grade 3 or 4 |
Withhold until clinically stable or permanently discontinue depending on severity |
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Grade 2 or 3 increased blood creatinine |
Withhold† |
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Grade 4 increased blood creatinine |
Permanently discontinue |
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Suspected SJS, TEN, or DRESS |
Withhold† |
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Confirmed SJS, TEN, or DRESS |
Permanently discontinue |
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Grade 2, 3, or 4 |
Permanently discontinue |
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Grade 2 |
Withhold† |
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Grade 3 or 4 |
Permanently discontinue |
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Other Adverse Reactions |
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Grade 1 or 2 |
Interrupt or slow the rate of infusion |
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Grade 3 or 4 |
Permanently discontinue |
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ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal |
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Preparation and Administration
Preparation
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- Visually inspect drug product for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard the vial if the solution is cloudy, discolored, or visible particles are observed.
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- Do not shake the vial.
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- Withdraw the required volume from the vial(s) of IMFINZI and transfer into an intravenous bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Mix diluted solution by gentle inversion. Do not shake the solution. The final concentration of the diluted solution should be between 1 mg/mL and 15 mg/mL.
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- Discard partially used or empty vials of IMFINZI.
Storage of Infusion Solution
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- IMFINZI does not contain a preservative.
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- Administer infusion solution immediately once prepared. If the infusion solution is not administered immediately and needs to be stored, the time from preparation until the completion of the infusion should not exceed:
- ∘
- 28 days in a refrigerator at 2°C to 8°C (36°F to 46°F)
- ∘
- 8 hours at room temperature up to 25°C (77°F)
- •
- Do not freeze.
- •
- Do not shake.
Administration
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- Administer infusion solution intravenously over 60 minutes through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.
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- Use separate infusion bags and filters for each drug product.
IMFINZI in Combination with Other Products
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- Administer all drug products as separate intravenous infusions.
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- Do not co-administer other drugs through the same infusion line.
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- For platinum-based chemotherapy, refer to Prescribing Information for administration information.
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- For pemetrexed therapy, refer to Prescribing Information for administration information.
Combination Regimens: Order of Infusions
IMFINZI in Combination with Tremelimumab-actl
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- Infuse tremelimumab-actl first, followed by IMFINZI on the same day of dosing.
IMFINZI in Combination with Tremelimumab-actl and Platinum-Based Chemotherapy
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- Infuse tremelimumab-actl first, followed by IMFINZI and then platinum-based chemotherapy on the day of dosing.
IMFINZI in Combination with Tremelimumab-actl and Pemetrexed Therapy
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- Infuse tremelimumab-actl first, followed by IMFINZI and then pemetrexed therapy on the day of dosing.
Combination Regimens: Infusion Instructions
IMFINZI in Combination with Tremelimumab-actl
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- Administer tremelimumab-actl over 60 minutes followed by a 60 minute observation period. Then administer IMFINZI as a separate intravenous infusion over 60 minutes.
IMFINZI in Combination with Tremelimumab-actl and Platinum-Based Chemotherapy/ Pemetrexed Therapy
Cycle 1
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- Infuse tremelimumab-actl over 1 hour. One to two hours after completion of tremelimumab-actl infusion, infuse IMFINZI over 1 hour. One to two hours after completion of IMFINZI infusion, administer platinum-based chemotherapy.
Subsequent Cycles
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- If there are no infusion reactions during cycle 1, subsequent cycles of IMFINZI can be given immediately after tremelimumab-actl. The time between the end of the IMFINZI infusion and the start of chemotherapy can be reduced to 30 minutes.
