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SAFETY

Please see the serious Warnings and
Precautions associated with IMFINZI.

Adverse Reactions

In resectable Stage IIA to IIIB (tumors ≥4 cm and/or node positive [N1, N2]) NSCLC with no known EGFR mutations or ALK rearrangements

Demonstrated safety profile with perioperative IMFINZI-based treatment1,2

Safety was evaluated from the start of neoadjuvant treatment (4 cycles) through resection and for up to 1 year of adjuvant therapy1,2

ADVERSE REACTIONS OCCURRING IN
≥10% OF PATIENTS IN THE
AEGEAN STUDY1

Adverse reaction IMFINZI with CT (N=401) Placebo with CT (N=398)
All Grades
(%) 		Grade 3 or 4
(%) 		All Grades
(%)		 Grade 3 or 4
(%)
Gastrointestinal disorders
Nausea 25 0.2 29 0.3
Constipation 25 0.2 21 0
Diarrhea* 14 1 13 1.3
Vomiting 11 0.7 11 1
General disorders and administration site conditions
Fatigue† 25 0 25 1.5
Skin and subcutaneous tissue disorders
Rash‡ 22 0.5 14 0.3
Pruritus 12 0.2 6 0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain§ 24 1 29 0.5
Metabolism and nutrition disorders
Decreased appetite 18 0.2 18 0.3
Nervous system disorders
Peripheral neuropathy|| 16 0.5 22 0.8
Endocrine disorders
Hypothyroidism 11 0 3.8 0
Respiratory, thoracic, and mediastinal disorders
Cough/productive cough 11 0 13 0
Pneumonia#** 11 3.5 10 3
COVID-19†† 11 0.2 9 0.8
Psychiatric disorders
Insomnia 10 0 12 0
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  • The most common adverse reactions (occurring in ≥20% of patients) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash1

SIMILAR INCIDENCE OF TREATMENT-
RELATED MAXIMUM
GRADE 3 OR 4
ADVERSE EVENTS AT FIRST INTERIM
ANALYSIS2

32.4% with the AEGEAN Regimen
32.9% with neoadjuvant CT alone
*
Includes colitis, diarrhea, enteritis, and proctitis.1
†
Includes fatigue and asthenia.1
‡
Includes dermatitis, dermatitis acneiform, drug eruption, eczema, eczema asteatotic, erythema, palmar‑erythrodysesthesia syndrome, pemphigoid, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, skin exfoliation, and urticarial dermatitis.1
§
Includes arthralgia, arthritis, back pain, bone pain, chest pain, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal discomfort, musculoskeletal stiffness, myalgia, neck pain, noncardiac chest pain, pain in extremity, and spinal pain.1
||
Includes dysesthesia, hypoesthesia, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, and polyneuropathy.1
Includes blood thyroid-stimulating hormone increased and hypothyroidism.1
#
Includes lower respiratory tract infection, lung abscess, paracancerous pneumonia, pneumonia, pneumonia aspiration, pneumonia bacterial, pneumonia chlamydial, pneumonia cryptococcal, pneumonia fungal, pneumonia pseudomonal, pneumonia streptococcal, pneumonia viral, and post-procedural pneumonia.1
**
Five Grade 5 events in the IMFINZI arm and four Grade 5 events in the placebo arm.1
††
Includes COVID-19 and COVID-19 pneumonia. Five Grade 5 events in the IMFINZI arm and one Grade 5 event in the placebo arm.1
ALK=anaplastic lymphoma kinase; CT=chemotherapy; EGFR=epidermal growth factor receptor; NSCLC=non-small cell lung cancer.
Laboratory Abnormalities
and Discontinuation Rates

Laboratory abnormalities worsening from baseline occurring in ≥20% of patients in the AEGEAN study1

SELECT LABORATORY
ABNORMALITIES1

Laboratory abnormality* IMFINZI with CT† Placebo with CT‡
All Grades
(%) 		Grade 3 or 4
(%) 		All Grades
(%)		 Grade 3 or 4
(%)
Hematology
Hemoglobin decreased 78 10 75 9
Leukocytes decreased 63 12 64 11
Neutrophils decreased 52 24 56 27
Platelets decreased 46 7 44 8
Lymphocytes decreased 41 11 37 9
Chemistry
Calcium corrected, decreased 51 3.3 52 4.5
Alanine aminotransferase increased 49 6 42 2
Aspartate aminotransferase increased 47 3.5 37 1.8
Potassium increased 33 1.5 29 2
Sodium decreased 35 5 33 6
Gamma glutamyl transferase increased 36 4.7 35 2.1
Creatinine increased 32 2.3 27 3.3
Amylase increased 25 4.7 24 3.6
Magnesium decreased 22 2.8 20 3.6
Lipase increased 23 4.9 24 7
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Discontinuation rate of IMFINZI or placebo due to adverse events
of any grade:
12% with the IMFINZI arm and 6% in the placebo arm2

*
Graded per NCI CTCAE, version 5.1
†
The denominator used to calculate the rate varied from 349 to 399 based on the number of patients with a baseline value and at least 1 post-treatment value.1
‡
The denominator used to calculate the rate varied from 333 to 398 based on the number of patients with a baseline value and at least 1 post-treatment value.1
CT=chemotherapy; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.
Safety by Phase

Safety by phase in the AEGEAN study1

Neoadjuvant phase of AEGEAN

A total of 401 patients received at least 1 dose of IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, and 398 patients received at least 1 dose of placebo in combination with platinum-containing chemotherapy as neoadjuvant treatment.

Serious adverse reactions occurred in 21% of patients who received IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment; the most frequent (≥1%) serious adverse reactions were pneumonia (2.7%), anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%), neutropenia (1%), and acute kidney injury (1%). Fatal adverse reactions occurred in 2% of patients, including death due to COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%), decreased appetite (0.2%), hemoptysis (0.2%), and death not otherwise specified (0.2%).

Permanent discontinuation of any study drug due to an adverse reaction occurred in 14% of patients who received IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment; the most frequent (>0.5%) adverse reactions that led to permanent discontinuation of any study drug were anemia (1.5%), neutropenia (0.7%), myelosuppression (0.7%), and periphery sensory neuropathy (0.7%). Permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6.7% of patients who received IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment; the most frequent (≥0.5%) adverse reactions that led to permanent discontinuation of IMFINZI were peripheral sensory neuropathy (0.7%) and pneumonitis (0.5%).

Of the 401 IMFINZI-treated patients and 398 placebo-treated patients who received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4), respectively, did not receive surgery due to adverse reactions. Adverse reactions that led to cancellation of surgery in the IMFINZI arm were COVID-19 pneumonia, HIV infection, pneumonitis, prostate cancer, colon cancer, pruritus, and colitis.

Of the 325 IMFINZI-treated patients who received surgery, 4% (n=15) experienced delay of surgery (a surgical delay is defined as on-study surgery occurring more than 40 days after the last dose of study treatment in the neoadjuvant period) due to adverse reactions. Of the 326 placebo-treated patients who received surgery, 4% (n=16) experienced delay of surgery due to adverse reactions.

Of the 325 IMFINZI-treated patients who received surgery, 6.5% (n=21) did not receive adjuvant treatment due to adverse reactions. Of the 326 placebo-treated patients who received surgery, 5.8% (n=19) did not receive adjuvant treatment due to adverse reactions.

Adjuvant phase of AEGEAN

A total of 265 patients in the IMFINZI arm and 254 patients in the placebo arm received at least 1 dose of adjuvant treatment.

Of the patients who received single-agent IMFINZI as adjuvant treatment, 13% experienced serious adverse reactions. The most frequent serious adverse reactions reported in >1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and COVID-19 (1.1%). Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease, and aortic aneurysm. Permanent discontinuation of adjuvant IMFINZI due to an adverse reaction occurred in 8% of patients. The most frequent (≥0.5%) adverse reactions that led to permanent discontinuation of adjuvant IMFINZI were pneumonitis (1.1%) and rash (0.8%).

ADVERSE EVENT SUMMARY FROM
SECOND INTERIM ANALYSIS3

Overall study period (including neoadjuvant, surgical, and adjuvant treatment phases)
Adverse events The AEGEAN
Regimen (N=401) 		Neoadjuvant CT
alone (N=398)
Any-grade all-causality AEs, n (%) 387 (96.5) 379 (95.2)
Serious AEs 157 (39.2) 126 (31.7)
Fatal AEs 23 (5.7) 15 (3.8)
Leading to discontinuation 51 (12.7) 25 (6.3)
Leading to cancellation of surgery 7 (1.7) 4 (1.0)
Max. Grade 3 or 4 175 (43.6) 172 (43.2)
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AEs=adverse events; CT=chemotherapy; HIV=human immunodeficiency virus.
EFFICACY PATIENT TYPES

SEE FULL INDICATIONS

IMFINZI, as a single agent, 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 (cCRT).

IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.

IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).

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).

IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).

IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).

IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).

+

IMPORTANT SAFETY INFORMATION

There are no contraindications for IMFINZI® (durvalumab) or IMJUDO® (tremelimumab-actl).

Indications:

IMFINZI, as a single agent, 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.

 

IMPORTANT SAFETY INFORMATION

There are no contraindications for IMFINZI® (durvalumab) or IMJUDO® (tremelimumab-actl).

Severe and Fatal 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 clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. 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 and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and IMJUDO 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, as a single agent, 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 (cCRT).

IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.

IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).

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).

IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).

IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).

IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test.

IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle-invasive bladder cancer (MIBC).

IMFINZI in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single agent IMFINZI, is indicated for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).

Immune-Mediated Pneumonitis

IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

  • IMFINZI as a Single Agent
    • In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), 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 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions.
    • The incidence of pneumonitis (including radiation pneumonitis) in patients with LS-SCLC following chemoradiation within 42 days prior to initiation of IMFINZI in ADRIATIC was 14% (37/262) in patients receiving IMFINZI and 6% (16/265) in patients receiving placebo. Of the patients who received IMFINZI (262), 0.4% had a fatal adverse reaction and 2.7% had Grade 3 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 or BTC when given in combination with chemotherapy.
  • IMFINZI with IMJUDO
    • Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions.

Immune-Mediated Colitis

IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal.
IMFINZI and IMJUDO 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.

  • IMFINZI as a Single Agent
    • Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions. Intestinal perforation has been observed in other studies of IMFINZI and IMJUDO.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Intestinal perforation and large intestine perforation were reported in 0.1% of patients.

Immune-Mediated Hepatitis

IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal.

  • IMFINZI as a Single Agent
    • Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune-mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4 (0.3%) and Grade 3 (4.1%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2%) adverse reactions.

Immune-Mediated Endocrinopathies

  • Adrenal Insufficiency: IMFINZI and IMJUDO can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.
    • IMFINZI as a Single Agent
      • Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
    • IMFINZI with IMJUDO
      • Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.8%) adverse reactions.
  • Hypophysitis: IMFINZI and IMJUDO 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.
    • IMFINZI as a Single Agent
      • Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI.
    • IMFINZI with IMJUDO
      • Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions.
  • Thyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism): IMFINZI and IMJUDO 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.
    • IMFINZI as a Single Agent
      • Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
      • Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI.
      • Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
    • IMFINZI with IMJUDO
      • Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO.
      • Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions.
      • Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy.
      • Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions.
      • Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions.
    • IMFINZI with Carboplatin and Paclitaxel
      • Immune-mediated hypothyroidism occurred in 14% (34/235) of patients receiving IMFINZI in combination with carboplatin and paclitaxel.
  • 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.
    • IMFINZI as a Single Agent
      • Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI.
    • IMFINZI with IMJUDO
      • Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including Grade 3 (0.3%) adverse reactions.

Immune-Mediated Nephritis with Renal Dysfunction

IMFINZI and IMJUDO can cause immune-mediated nephritis.

  • IMFINZI as a Single Agent
    • Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions.

Immune-Mediated Dermatology Reactions

IMFINZI and IMJUDO 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), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.

  • IMFINZI as a Single Agent
    • Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions.

Immune-Mediated Pancreatitis

IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) 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 and IMJUDO or were reported with the use of other immune-checkpoint inhibitors.

  • 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, other transplant (including corneal graft) rejection.

Infusion-Related Reactions

IMFINZI and IMJUDO 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 and IMJUDO based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses.

  • IMFINZI as a Single Agent
    • Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.
  • IMFINZI with IMJUDO
    • Infusion-related reactions occurred in 2.6% (10/388) of patients receiving IMFINZI and IMJUDO.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, 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 their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO.

Lactation

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

Adverse Reactions

    Unresectable Stage III NSCLC
  • 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 pneumonia (7%) and pneumonitis/radiation pneumonitis (3.4%).
  • 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.
    • Resectable NSCLC
  • In patients with resectable NSCLC in the AEGEAN study, the most common adverse reactions (occurring in ≥20% of patients) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash.
  • In patients with resectable NSCLC in the neoadjuvant phase of the AEGEAN study receiving IMFINZI in combination with platinum-containing chemotherapy (n=401), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6.7% of patients. Serious adverse reactions occurred in 21% of patients. The most frequent (≥1%) serious adverse reactions were pneumonia (2.7%), anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%), neutropenia (1%), and acute kidney injury (1%). Fatal adverse reactions occurred in 2% of patients, including death due to COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%), decreased appetite (0.2%), hemoptysis (0.2%), and death not otherwise specified (0.2%). Of the 401 IMFINZI-treated patients who received neoadjuvant treatment and 398 placebo-treated patients who received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4), respectively, did not receive surgery due to adverse reactions.
  • In patients with resectable NSCLC in the adjuvant phase of the AEGEAN study receiving IMFINZI as a single agent (n=265), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 8% of patients. Serious adverse reactions occurred in 13% of patients. The most frequent serious adverse reactions reported in >1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and COVID-19 (1.1%). Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease and aortic aneurysm.
    • Metastatic NSCLC
  • In patients with mNSCLC in the POSEIDON study receiving IMFINZI and IMJUDO plus platinum-based chemotherapy (n=330), the most common adverse reactions (occurring in ≥20% of patients) were nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased appetite (28%), rash (27%), and diarrhea (22%).
  • In patients with mNSCLC in the POSEIDON study receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy (n=330), permanent discontinuation of IMFINZI or IMJUDO due to an adverse reaction occurred in 17% of patients. Serious adverse reactions occurred in 44% of patients, with the most frequent serious adverse reactions reported in at least 2% of patients being pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse reactions occurred in a total of 4.2% of patients.
    • Limited-stage Small Cell Lung Cancer
  • In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), the most common adverse reactions occurring in ≥20% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (38%), and fatigue (21%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonitis or radiation pneumonitis and pneumonia.
  • In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), IMFINZI was permanently discontinued due to adverse reactions in 16% of the patients receiving IMFINZI. Serious adverse reactions occurred in 30% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in ≥1% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (12%), and pneumonia (5%). Fatal adverse reactions occurred in 2.7% of patients who received IMFINZI including pneumonia (1.5%), cardiac failure, encephalopathy and pneumonitis (0.4% each).
    • Extensive-stage Small Cell Lung Cancer
  • In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%), and alopecia (31%). 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.
    • Locally Advanced or Metastatic Biliary Tract Cancers
  • In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse reactions (occurring in ≥20% of patients) were fatigue (42%), nausea (40%), constipation (32%), decreased appetite (26%), abdominal pain (24%), rash (23%), and pyrexia (20%).
  • In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to adverse reactions occurred in 6% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and acute kidney injury (2.4%). Fatal adverse reactions occurred in 3.6% of patients receiving IMFINZI plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients), and upper gastrointestinal hemorrhage (2 patients).
    • Unresectable Hepatocellular Carcinoma
  • In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), the most common adverse reactions (occurring in ≥20% of patients) were rash (32%), diarrhea (27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%), and abdominal pain (20%).
  • In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), serious adverse reactions occurred in 41% of patients. Serious adverse reactions in >1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8% of patients who received IMFINZI and IMJUDO, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). Permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients.
    • Primary advanced or Recurrent dMMR Endometrial Cancer
  • In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent (n=44), the most common adverse reactions, including laboratory abnormalities (occurring in >20% of patients) were peripheral neuropathy (61%), musculoskeletal pain (59%), nausea (59%), alopecia (52%), fatigue (41%), abdominal pain (39%), constipation (39%), rash (39%), decreased magnesium (36%), increased ALT (32%), increased AST (30%), diarrhea (27%), vomiting (27%), cough (27%), decreased potassium (25%), dyspnea (25%), headache (23%), increased alkaline phosphatase (20%), and decreased appetite (18%). The most common Grade 3 or 4 adverse reactions (≥3%) were constipation (4.5%) and fatigue (4.5%).
  • In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent (n=44), permanent discontinuation of IMFINZI due to adverse reactions occurred in 11% of patients. Serious adverse reactions occurred in 30% of patients who received IMFINZI with carboplatin and paclitaxel; the most common serious adverse reactions (≥4%) were constipation (4.5%) and rash (4.5%).
    • Muscle-Invasive Bladder Cancer (MIBC)
  • In patients with MIBC, the most common adverse reactions, including laboratory abnormalities, in the overall study (occurring in ≥20% of patients) were decreased hemoglobin, decreased neutrophils, increased blood creatinine, decreased sodium, nausea, increased ALT, decreased calcium, decreased platelets, fatigue, increased potassium, decreased lymphocytes, increased AST, constipation, decreased magnesium, decreased appetite, increased alkaline phosphate, rash, pyrexia, diarrhea, vomiting and abdominal pain.
  • In patients with MIBC in the neoadjuvant phase of the NIAGARA study receiving IMFINZI in combination with gemcitabine and cisplatin (n=530), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 9% of patients. Serious adverse reactions occurred in 24% of patients; the most frequent (≥1%) serious adverse reactions were pulmonary embolism (1.9%), febrile neutropenia (1.5%), acute kidney injury (1.3%), thrombocytopenia (1.3%), urinary tract infection (1.3%), and pneumonia (1.3%). Fatal adverse reactions occurred in 1.1% of patients including sepsis, myocardial infarction, and pulmonary embolism (0.2% each). One fatal adverse reaction of pneumonia was reported in 1 (0.2%) patient in the post-surgery phase before adjuvant treatment started. Of the 530 patients in the IMFINZI treatment arm and 526 patients in the chemotherapy treatment arm who received neoadjuvant treatment, 1 (0.2%) patient in each treatment arm did not receive surgery due to adverse reactions. The adverse reaction that led to cancellation of surgery in the IMFINZI treatment arm was interstitial lung disease.
  • In patients with MIBC in the adjuvant phase of the NIAGARA study receiving IMFINZI as a single agent (n=383), permanent discontinuation of adjuvant IMFINZI due to an adverse reaction occurred in 5% of patients. Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions (occurring in ≥1% of patients) were urinary tract infection (7%), acute kidney injury (3.7%), hydronephrosis (2.1%), pyelonephritis (2.1%), urosepsis (1.8%) and sepsis (1.6%). Fatal adverse reactions occurred in 1.8% of patients, including COVID-19, severe acute respiratory syndrome, cardiopulmonary failure, gastrointestinal hemorrhage, and chronic hepatic failure (0.3% each).
    • Resectable Gastric Cancer/Gastroesophageal Junction Adenocarcinoma (GC/GEJC)
  • In patients with resectable GC/GEJC, the most common adverse reactions in the overall study (occurring in ≥20% of patients) were diarrhea, nausea, peripheral neuropathy, fatigue, alopecia, decreased appetite, rash, abdominal pain, vomiting, musculoskeletal pain, pyrexia, and stomatitis.
  • In patients with resectable GC/GEJC in the neoadjuvant phase of the MATTERHORN study receiving IMFINZI in combination with FLOT chemotherapy (n=475), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 2.5% of patients. Serious adverse reactions occurred in 21% of patients; the most frequent (≥2%) serious adverse reaction was diarrhea (2.5%). Deaths occurred in 1.9% of patients; deaths ≥2 patients included septic shock (0.6%) and acute coronary syndrome (0.4%). Of the 475 patients in the IMFINZI + FLOT chemotherapy treatment arm and 469 patients in the placebo + FLOT chemotherapy treatment arm who received neoadjuvant treatment, 0.6% and 0.4% of patients, respectively, did not receive surgery due to adverse reactions, and 2.3% and 2.6% of patients, respectively, had a delay in surgery due to ARs.
  • In patients with resectable GC/GEJC in the adjuvant phase of the MATTERHORN study receiving IMFINZI in combination with FLOT chemotherapy (n=365), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 7% of patients. Serious adverse reactions occurred in 29% of patients; the most frequent (≥2%) serious adverse reaction was pneumonia (2.5%). Deaths occurred in 2.2% of patients; deaths ≥2 patients included gastrointestinal perforation (0.5%) and COVID-19 (0.5%).
  • In patients with resectable GC/GEJC in the adjuvant phase of the MATTERHORN study receiving IMFINZI alone (n=345), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6% of patients. Serious adverse reactions occurred in 14% of patients. Deaths occurred in 1.7% of patients; deaths ≥2 patients included gastrointestinal perforation (0.6%) and COVID-19 (0.6%).

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

Indications:

IMFINZI, as a single agent, 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 (cCRT).

IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.

IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).

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).

IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).

IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).

IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test.

IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle-invasive bladder cancer (MIBC).

IMFINZI in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single agent IMFINZI, is indicated for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).

Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO.

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