IMFINZI Nurse Center

Who is IMFINZI for?

IMFINZI® (durvalumab) is FDA approved for 3 types of cancer.1

Education and resources for oncology nurses

The IMFINZI Nurse Center is designed to help you use IMFINZI in your practice. For patient counseling materials, look for the “Patient Connection” downloads throughout the site.

Preparing for treatment with IMFINZI

 

For adult patients with non-small cell lung cancer (NSCLC) when1:

The cancer has not spread outside the chest

AND

The cancer cannot be removed by surgery

AND

The cancer has not progressed after concurrent platinum-based chemotherapy and radiation therapy

 
 

For adult patients with extensive-stage small cell lung cancer (ES-SCLC) when1:

The patient has not been previously treated

AND

The cancer has spread within the lungs (or to other parts of the body)

 
 

For adult patients with urothelial carcinoma (UC) when1:

The patient has been previously treated with chemotherapy containing platinum which did not work or is no longer working

AND

The cancer has spread or cannot be removed by surgery

 
  COUNSELING TIP

Understanding these indications may help you answer patients’ questions about their cancer and why IMFINZI is part of their treatment plan.

 

How does IMFINZI work?

IMFINZI blocks the interaction of PD-L1 with PD-1 and CD801

  • IMFINZI is a human immunoglobulin G1 kappa (IgG1K) monoclonal antibody that blocks the interaction of PD-L1 with PD-1 and CD80 (B7.1)
  • Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without including antibody-dependent cell-mediated cytotoxicity (ADCC)
  • PD-L1 blockade with IMFINZI led to increased T-cell activation in vitro and decreased tumor size in co-engrafted human tumor and immune cell xenograft mouse models

PD-L1=programmed death-ligand 1; PD-1=programmed cell death protein 1; CD80=cluster of differentiation 80.

Dosage and administration

Recommended dosage1

IMFINZI is administered as an IV infusion with no premedication required1

For UC or Unresectable Stage III NSCLC: Weight-based dose (10 mg/kg)

60-MINUTE IV INFUSION

Q2W

  • IMFINZI fixed dose
  • IMFINZI

  • until disease progression or
    unacceptable toxicity (NSCLC:
    Maximum of 26 doses [12 months])

 

IMFINZI may be administered until disease progression, unacceptable toxicity, or up to 26 doses (12 months)*†

 

For ES-SCLC: Fixed 1500-mg dose

INDUCTION

Q3W x 4 CYCLES

  • IMFINZI fixed dose
  • IMFINZI
    1500-mg fixed dose

  • Additional dose
  • PLATINUM-BASED
    CHEMOTHERAPY

  • Additional dose
  • ETOPOSIDE

MAINTENANCE

Q4W

  • IMFINZI fixed dose
  • IMFINZI
    1500-mg fixed dose

  • until disease progression or
    unacceptable toxicity

  • When administering IMFINZI in combination with chemotherapy, administer IMFINZI prior to chemotherapy on the same day
  • EP consists of etoposide 80 mg/m2 to 100 mg/m2 with either carboplatin AUC 5 mg/mL/min or 6 mg/mL/min or cisplatin 75 mg/m2 to 80 mg/m2. For more information, please refer to the Prescribing Information for each treatment

IV=intravenous; Q2W=once every 2 weeks; Q3W=once every 3 weeks; Q4W=once every 4 weeks; EP=etoposide and either carboplatin or cisplatin; AUC=area under the curve.

*Based on Q2W dosing for 52 weeks.2

Refer to Prescribing Information for information on dosage modifications.

For ES-SCLC, patients with a body weight of ≤30 kg must receive weight-based dosing, equivalent to IMFINZI 20 mg/kg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 20 mg/kg every 4 weeks as a single agent until body weight increases to >30 kg.1

Dosage forms and strengths1

  • Dosage forms and strengths icon

    Available in 120 mg/2.4 mL (50 mg/mL) and 500 mg/10 mL (50 mg/mL) single-dose vials. Clear to opalescent, colorless to slightly yellow solution

Preparation1

  • Eye icon

    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

  • Do not shake the vile icon

    Do not shake the vial

  • Intravenous bag icon

    Withdraw the required volume from the vial(s) of IMFINZI and transfer into an IV 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

  • Disposal icon

    Discard partially used or empty vials of IMFINZI

Storage of infusion solution1

IMFINZI does not contain a preservative. Administer infusion solution immediately once prepared. If infusion solution is not administered immediately and needs to be stored, the total time from vial puncture to the start of the administration should not exceed:

  • Refrigerator storage icon

    24 hours in a refrigerator at 2°C to 8°C (36°F to 46°F)

  • Room temperature icon

    8 hours at room temperature up to 25°C (77°F)

  • Do not freeze icon

    Do not freeze

  • Do not shake the IV bag icon

    Do not shake

Administration1

  • Administration time icon

    Administer infusion solution intravenously over 60 minutes through an IV line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter

  • Do not co-administer icon

    Do not coadminister other drugs through the same infusion line

  COUNSELING TIPS

Help your patients prepare for treatment by telling them:

Why IMFINZI is part of their treatment plan

How immunotherapy works

When, where, and how often they will receive IMFINZI infusions

 
  DOWNLOAD AND SHARE

Helpful downloads when preparing for treatment

For nurses icon

For you:

For patients icon

For your patients:

DownloadPlease choose a resource to download.
 

Monitoring patients & managing their imARs

Immune-mediated adverse reactions (imARs) can be different than what is expected with chemotherapy. It's important to understand the safety profile of IMFINZI and encourage your patients to track any signs and symptoms they may experience.

Educate your patients about IMFINZI

Educate your patients

Make sure your patients:

  • Understand imAR symptoms to look for
  • Immediately report anything of concern to you and/or the oncologist
  • Go directly to the oncologist’s office for evaluation/treatment
Monitor your patient’s health while taking IMFINZI

Monitor their health

  • Regularly perform blood tests (CBC, renal, hepatic, pancreatic, thyroid)
  • Schedule patients for regular visits for blood tests and monitoring of symptoms
  • Encourage patients to use their symptom tracker
Create an action plan

Create an action plan

  • Follow a clear management algorithm for all grades of toxicities
  • Understand when a specialist should be contacted to help manage imARs
Intervene when necessary

Intervene when necessary

  • Take immediate action, even for Grade 1 toxicities
    • Hold dosing until symptoms resolve
    • Start with OTC medications; initiate steroids early if needed
  • Refer to the imAR Navigator App or the imAR Management Handbook for more information
  DOWNLOAD
IMFINZI imAR Navigator App

Download the imAR Navigator App now

Apple app store logoGoogle Play logo

 

CBC=complete blood count; OTC=over-the-counter.

Dosage modifications

If your patient is experiencing imARs greater than Grade 1, you may need to withhold or discontinue treatment with IMFINZI. Refer to the table below for guidance.

Dosage reduction of IMFINZI is not recommended1

Withold IMFINZI WITHHOLD IMFINZI*

Specific immune-mediated adverse reactions

Pneumonitis: Grade 2

Colitis: Grade 2 or 3

Hepatitis with no tumor involvement of the liver:

ALT or AST >3 and up to 8 × ULN

or

Total bilirubin >1.5 and up to 3 × ULN

Hepatitis with tumor involvement of the liver†‡:

ALT or AST at baseline >1 and up to 3 × ULN and increases to >5 and up to 10 × ULN

or

ALT or AST at baseline >3 and up to 5 × ULN and increases to >8 and up to 10 × ULN

Endocrinopathies:Grade 3 or 4, withhold until stable

Nephritis with renal dysfunction: Grade 2 or 3 increased blood creatinine

Exfoliative dermatologic conditions: Suspected SJS, TEN, or DRESS

Myocarditis: N/A

Neurological toxicities: Grade 2

General guidance

  • Grade 3 immune-mediated adverse reactions

Other adverse reactions

Infusion-related reactions: Grade 1 or 2, interrupt or slow rate of infusion

Resume IMFINZI

After complete or partial resolution (Grade 0 or 1) and corticosteroid taper

Permanently discontinue IMFINZI PERMANENTLY DISCONTINUE IMFINZI*

Specific immune-mediated adverse reactions

Pneumonitis: Grade 3 or 4

Colitis: Grade 4

Hepatitis with no tumor involvement of the liver:

ALT or AST >8 × ULN

or

Total bilirubin >3 × ULN

Hepatitis with tumor involvement of the liver:

ALT or AST >10 × ULN

or

Total bilirubin >3 × ULN

Endocrinopathies: Grade 3 or 4, permanently discontinue
depending on severity

Nephritis with renal dysfunction: Grade 4 increased blood creatinine

Exfoliative dermatologic conditions: Confirmed SJS, TEN, or DRESS

Myocarditis: Grade 2, 3, or 4

Neurological toxicities: Grade 3 or 4

General guidance

  • Grade 4 immune-mediated adverse reactions
  • Recurrent Grade 3 immune-mediated adverse reactions that require systemic immunosuppressive treatment
  • When withholding IMFINZI, discontinue if no complete or partial resolution (Grade 0 or 1) occurs or if unable to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of corticosteroid initiation

Other adverse reactions

Infusion-related reactions: Grade 3 or 4

Prescribing Information has additional information for dosage modification and management specific to adverse reactions.

ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal; SJS=Stevens Johnson Syndrome; TEN=toxic epidermal necrolysis; DRESS=Drug Rash with Eosinophilia and Systemic Symptoms; N/A=not applicable.

*Based on National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.

Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone 10 mg per day or less (or equivalent) within 12 weeks of initiating steroids.

If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue IMFINZI based on recommendations for hepatitis with no liver involvement.

  COUNSELING TIPS

Remind your patients1-3

Report any signs, symptoms, or changes from baseline

imARs may be different from side effects associated with chemotherapy

imARs may develop after the first dose, or long after a course of immunotherapy has ended

 
  DOWNLOAD AND SHARE

Helpful downloads for monitoring patients & managing imARs

For nurses icon

For you:

For patients icon

For your patients:

DownloadPlease choose a resource to download.
 

Find more resources

Supporting and empowering patients to take ownership of their treatment with IMFINZI® (durvalumab)

Lighthouse empowers patients to take an active role in their treatment journey by facilitating relationships with Nurse Advocates who:

  • Provide 24/7 personalized attention to your patients and their caregivers
  • Encourage your patients to keep you updated on their treatment experience so you can make better decisions for their care
  • Partner with your patients to help them better understand what they can expect during and after treatment with IMFINZI
  • Enable you and your practice to remain informed about your patients' treatment experience

To learn more about how patients will experience the Lighthouse program, call 1-855-LHOUSE1 (1-855-546-8731).

Helping patients access the care they need

The AstraZeneca Access 360TM program provides personal support to connect patients to affordability programs and streamline access and reimbursement for IMFINZI. Access 360TM provides:

  • Assistance with understanding patient insurance coverage and pharmacy options
  • Prior authorization support
  • Claims and appeal process support

To learn more about the AstraZeneca Access 360TM program, please call 1-844-ASK-A360 (1-844-275-2360) Monday-Friday, 8 AM-8 PM ET, or visit www.MyAccess360.com.

 

Choose the most convenient method of enrollment

CALL Access 360 at 1-844-ASK-A360 (1-844-275-2360) Monday to Friday, 8 AM-8 PM EST

VISIT the provider portal at

ProviderPortal.MyAccess360.com

 

Nurse Educators can:

  • Deliver disease-state education to nurses and other healthcare staff at your facility
  • Provide education on the early recognition and management of adverse events associated with AstraZeneca therapies
  • Deliver educational tools and resources designed for nurses, patients, and caregivers
 

Select a state to find an ONE near you:

 
  DOWNLOAD AND SHARE

IMFINZI Nurse Center Library

For nurses icon

For you:

For patients icon

For your patients:

DownloadPlease choose a resource to download.
 

Important Safety Information

There are no contraindications for IMFINZI® (durvalumab).

Immune-Mediated Adverse Reactions

Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI depending on severity. See Dosing and Administration for specific details. In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Indications

IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

Immune-Mediated Pneumonitis

IMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.0% (28/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 16.6% (79/475) in patients receiving IMFINZI and 13.2% (31/234) in patients receiving placebo. Of the 79 patients who received IMFINZI, 1.1% were fatal and 2.5% were Grade 3-4 adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC when in combination with chemotherapy.

Immune-Mediated Colitis

IMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.6% (31/1889) of patients receiving IMFINZI, including Grade 4 (0.1%) and Grade 3 (0.3%) adverse reactions.

Immune-Mediated Hepatitis

IMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1.0% (19/1889) of patients receiving IMFINZI, including fatal (<0.1%) and Grade 3 (0.6%) adverse reactions.

Immune-Mediated Endocrinopathies

  • Adrenal Insufficiency: IMFINZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Immune-mediated adrenal insufficiency occurred in 0.4% (7/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
  • Hypophysitis: IMFINZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI.
  • Thyroid disorders: IMFINZI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.
  • Thyroiditis: Immune-mediated thyroiditis occurred in 0.4% (7/1889) of patients receiving IMFINZI.
  • Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 1.4% (27/1889) of patients receiving IMFINZI.
  • Hypothyroidism: Immune-mediated hypothyroidism occurred in 7.3% (137/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
  • Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Grade 3 immune-mediated type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI.

Immune-Mediated Nephritis with Renal Dysfunction

IMFINZI can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (5/1889) of patients receiving IMFINZI, including Grade 3 (0.1%) adverse reactions.

Immune-Mediated Dermatology Reactions

IMFINZI can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), have occurred with PD-1/L-1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Immune-mediated rash or dermatitis occurred in 1.6% (30/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.

Other Immune-Mediated Adverse Reactions

The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI or were reported with the use of other PD-1/PD-L1 blocking antibodies.

  • Cardiac/vascular: Myocarditis, pericarditis, vasculitis.
  • Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.
  • Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
  • Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.
  • Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic.
  • Endocrine: Hypoparathyroidism
  • Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection.

Infusion-Related Reactions

IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI based on the severity. See Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.

Complications of Allogeneic HSCT after IMFINZI

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMFINZI and for at least 3 months after the last dose of IMFINZI.

Lactation

There is no information regarding the presence of IMFINZI in human milk; however, because of the potential for adverse reactions in breastfed infants from IMFINZI, advise women not to breastfeed during treatment and for at least 3 months after the last dose.

Adverse Reactions

  • In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (≥20%) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonitis/radiation pneumonitis (3.4%) and pneumonia (7%)
  • In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2%) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms
  • In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (≥20%) were nausea, fatigue/asthenia, and alopecia. The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%)
  • In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy

The safety and effectiveness of IMFINZI have not been established in pediatric patients.

Indications

IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

Please see complete Prescribing Information, including Medication Guide.

You may report side effects related to AstraZeneca products by clicking here.

Important Safety Information

There are no contraindications for IMFINZI® (durvalumab).

Immune-Mediated Adverse Reactions

Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI depending on severity. See Dosing and Administration for specific details. In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

IMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.0% (28/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 16.6% (79/475) in patients receiving IMFINZI and 13.2% (31/234) in patients receiving placebo. Of the 79 patients who received IMFINZI, 1.1% were fatal and 2.5% were Grade 3-4 adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC when in combination with chemotherapy.

Immune-Mediated Colitis

IMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.6% (31/1889) of patients receiving IMFINZI, including Grade 4 (0.1%) and Grade 3 (0.3%) adverse reactions.

Immune-Mediated Hepatitis

IMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1.0% (19/1889) of patients receiving IMFINZI, including fatal (<0.1%) and Grade 3 (0.6%) adverse reactions.

Immune-Mediated Endocrinopathies

  • Adrenal Insufficiency: IMFINZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Immune-mediated adrenal insufficiency occurred in 0.4% (7/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
  • Hypophysitis: IMFINZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI.
  • Thyroid Disorders: IMFINZI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.
  • Thyroiditis: Immune-mediated thyroiditis occurred in 0.4% (7/1889) of patients receiving IMFINZI.
  • Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 1.4% (27/1889) of patients receiving IMFINZI.
  • Hypothyroidism: Immune-mediated hypothyroidism occurred in 7.3% (137/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
  • Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Grade 3 immune-mediated type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI.

Immune-Mediated Nephritis with Renal Dysfunction

IMFINZI can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (5/1889) of patients receiving IMFINZI, including Grade 3 (0.1%) adverse reactions.

Immune-Mediated Dermatology Reactions

IMFINZI can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), have occurred with PD-1/L-1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Immune-mediated rash or dermatitis occurred in 1.6% (30/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.

Other Immune-Mediated Adverse Reactions

The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI or were reported with the use of other PD-1/PD-L1 blocking antibodies.

  • Cardiac/vascular: Myocarditis, pericarditis, vasculitis.
  • Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.
  • Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
  • Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.
  • Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic.
  • Endocrine: Hypoparathyroidism
  • Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection.

Infusion-Related Reactions

IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI based on the severity. See Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.

Complications of Allogeneic HSCT after IMFINZI

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMFINZI and for at least 3 months after the last dose of IMFINZI.

Lactation

There is no information regarding the presence of IMFINZI in human milk; however, because of the potential for adverse reactions in breastfed infants from IMFINZI, advise women not to breastfeed during treatment and for at least 3 months after the last dose.

Adverse Reactions

  • In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (≥20%) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonitis/radiation pneumonitis (3.4%) and pneumonia (7%)
  • In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2%) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms

The safety and effectiveness of IMFINZI have not been established in pediatric patients.