Imfinzi Drug Information

Patient Selection Advanced or Recurrent dMMR Endometrial Cancer Select patients for treatment based on the presence of dMMR in tumor specimens. Information on FDA-authorized tests for the detection of dMMR status in endometrial cancer is available at https://www.fda.gov/companiondiagnostics.

Recommended Dosage

The recommended dosages for IMFINZI as a single agent and IMFINZI in combination with other therapeutic agents are presented in Table 1. The recommended dosage schedule and regimens for IMFINZI for the treatment of metastatic NSCLC are provided in Tables 2 and 3. Administer IMFINZI as a 60 minute intravenous infusion after dilution.

Table 1. Weigh patients prior to each infusion. Calculate the appropriate dose using Table 3 below based on the patient’s weight and tumor histology.

Table 2. Recommended Dosage Schedule for Metastatic NSCLC IMFINZI intravenous infusion over 60 minutes. X X X X X X X X Tremelimumab-actl if patients receive fewer than 4 cycles of platinum-based chemotherapy, the remaining cycles of tremelimumab-actl (up to a total of 5) should be given after the platinum-based chemotherapy phase, in combination with IMFINZI, every 4 weeks.

X X X X X Chemotherapy X X X X X optional pemetrexed therapy from week 12 until disease progression or intolerable toxicity for patients with non-squamous disease who received treatment with pemetrexed and carboplatin/cisplatin. X X X Table 3. Recommended Regimen and Dosage for Metastatic NSCLC s 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 or chemotherapy for adverse reactions that require management different from these general guidelines are summarized in Table 4.

Table 4. Recommended

Preparation and Administration Preparation •

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 vial. • 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. • Discard partially used or empty vials of IMFINZI. Storage of Infusion Solution • IMFINZI does not contain a preservative. • 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 • 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. • Use separate infusion bags and filters for each drug product. IMFINZI in Combination with Other Products • Administer all intravenous drug products as separate infusions. • Do not co-administer other intravenous drugs through the same infusion line. • For platinum-based chemotherapy, refer to Prescribing Information for administration information. • For pemetrexed therapy, refer to Prescribing Information for administration information. • For BCG therapy, refer to BCG Prescribing Information for administration information.

Combination Regimens: Order of Administration IMFINZI in Combination with Tremelimumab-actl • Infuse tremelimumab-actl first, followed by IMFINZI on the same day of dosing. IMFINZI in Combination with Tremelimumab-actl and Platinum-Based Chemotherapy • 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 • Infuse tremelimumab-actl first, followed by IMFINZI and then pemetrexed therapy on the day of dosing.

IMFINZI in Combination with Carboplatin and Paclitaxel • Infuse IMFINZI first and then carboplatin and paclitaxel on the same day of dosing. IMFINZI in combination with BCG • If IMFINZI is given on the same day as BCG, infuse IMFINZI first, then administer BCG as an intravesical instillation. Combination Regimens: Infusion Instructions IMFINZI in Combination with Tremelimumab-actl • 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 • Infuse tremelimumab-actl over 60 minutes. One to two hours after completion of tremelimumab-actl infusion, infuse IMFINZI over 60 minutes.

One to two hours after completion of IMFINZI infusion, administer platinum-based chemotherapy. Subsequent Cycles • 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.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described in the WARNINGS AND PRECAUTIONS section reflect exposure to IMFINZI as a single agent in a total of 1,889 patients enrolled in the PACIFIC study (a randomized, placebo-controlled study that enrolled 475 patients with unresectable Stage III NSCLC), Study 1108 (an open-label, single-arm, multicohort study that enrolled 970 patients with advanced solid tumors), and an additional open-label, single-arm study (ATLANTIC Study) that enrolled 444 patients with advanced solid tumors, including NSCLC. In these studies, months or more.

The data also reflect exposure to IMFINZI 1,500 mg every 4 weeks as a single agent in 262 patients from the ADRIATIC study (a randomized, double-blind study in patients with LS-SCLC) and to IMFINZI in combination with chemotherapy in 265 patients from the CASPIAN study (a randomized, open-label study in patients with ES-SCLC) and in 338 patients from the TOPAZ-1 study (a randomized, double-blind study in patients with BTC). In the CASPIAN and TOPAZ-1 studies, IMFINZI was administered at a dose of 1,500 mg every 3 or 4 weeks. Among the months or more.

The data also reflect exposure to IMFINZI 1,500 mg in combination with tremelimumab-actl 300 mg in 388 patients in HIMALAYA. The data described in this section reflect exposure to IMFINZI in patients with unresectable Stage III NSCLC enrolled in the PACIFIC study, in patients with metastatic NSCLC enrolled in the POSEIDON study, in patients with LS-SCLC enrolled in the ADRIATIC study, in patients with ES-SCLC enrolled in the CASPIAN study, in patients with BTC enrolled in the TOPAZ 1 study, in patients with uHCC included in the HIMALAYA study, in patients with dMMR endometrial cancer enrolled in the DUO-E study, in patients with resectable NSCLC enrolled in the AEGEAN study, in patients with BCG-naïve, high-risk NMIBC enrolled in the POTOMAC study, and in patients with MIBC enrolled in the NIAGARA study. Non-Small Cell Lung Cancer Neoadjuvant and Adjuvant Treatment of Resectable NSCLC – AEGEAN The safety of IMFINZI in combination with neoadjuvant platinum-containing chemotherapy followed by surgery, and continued adjuvant treatment with IMFINZI as a single agent after surgery, was investigated in AEGEAN, a randomized, double-blind, placebo-controlled, multicenter study for patients with resectable NSCLC (Stage IIA to select Stage IIIB ); squamous or non-squamous.

Safety data are available for the 799 patients who received IMFINZI in combination with chemotherapy (n=401) or placebo in combination with chemotherapy (n=398). The median age of patients who received Hispanic or Latino. The most common adverse reactions (occurring in ≥ 20% of patients) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash.

Table 5 summarizes the adverse reactions that occurred in (≥ 10%) patients treated with IMFINZI in combination with chemotherapy. Table 5. 0 Table 6 summarizes the laboratory abnormalities in patients treated with IMFINZI in combination with chemotherapy. Table 6.

Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with Disease Who Received 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. Fatal adverse reactions occurred in 2% of patients, including death due to %. 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 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 8 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. Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease and aortic aneurysm. The most frequent (≥0.5%) adverse reaction that led to permanent discontinuation of adjuvant IMFINZI was pneumonitis (1.1%) and rash (0.8%).

Unresectable Stage III NSCLC - PACIFIC The safety of IMFINZI in patients with Stage III NSCLC who completed concurrent platinum-based chemoradiotherapy within 42 days prior to initiation of study drug was evaluated in the PACIFIC study, a multicenter, randomized, double-blind, placebo-controlled study. A total of 475 patients received IMFINZI 10 mg/kg intravenously every 2 weeks. The study excluded patients who had disease progression following chemoradiation, with active or prior autoimmune disease within 2 years of initiation of the study or with medical conditions that required systemic immunosuppression.

The study population characteristics were: median age of % had WHO performance status (PS) of 1. All patients received definitive radiotherapy as per protocol, of which 92% received a total radiation dose of 54 Gy to 66 Gy. The median duration of exposure to IMFINZI was 10 months (range: 0.2 to 12.6).

IMFINZI was discontinued due to adverse reactions in 15% of patients. The most common adverse reactions leading to IMFINZI discontinuation were pneumonitis or radiation pneumonitis in 6% of patients. Serious adverse reactions occurred in 29% of patients receiving IMFINZI.

The most frequent serious adverse reactions reported in at least 2% of patients 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 most common adverse reactions (occurring in ≥ 20% of patients) were cough, fatigue, pneumonitis or radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash.

Table 7 summarizes the adverse reactions that occurred in at least 0 Other adverse reactions occurring in less than 10% of patients treated with IMFINZI were dysphonia, dysuria, night sweats, peripheral edema, and increased susceptibility to infections. Table 8 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with IMFINZI. Table 8.

Laboratory Abnormalities Worsening from Baseline Occurring in ≥ Metastatic NSCLC - POSEIDON The safety of IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy in patients with metastatic NSCLC was evaluated in POSEIDON (NCT03164616), a randomized, open-label, multicenter, active-controlled study. Treatment was continued with IMFINZI as a single agent (or with IMFINZI and histologically-based pemetrexed for non-squamous patients based on the investigator’s decision) until disease progression or unacceptable toxicity. The study excluded patients with active or prior autoimmune disease or with medical conditions that required systemic corticosteroids or immunosuppressants.

The median age of patients who received IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy was % ECOG performance of 1. Fatal adverse reactions occurred in a total of 4.2% of patients receiving IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy. Permanent discontinuation of IMFINZI or tremelimumab-actl due to an adverse reaction occurred in 17% of the patients.

Adverse reactions which resulted in permanent discontinuation of IMFINZI or tremelimumab-actl in > 2% of patients included pneumonia. Dosage interruption or delay of IMFINZI and tremelimumab-actl due to an adverse reaction occurred in 41% of patients. Adverse reactions which required dosage interruption or delay of IMFINZI and tremelimumab-actl in > 1% of patients included anemia, leukopenia/white blood cell count decreased, pneumonia, pneumonitis, colitis, diarrhea, hepatitis, rash, asthenia, amylase increased, alanine aminotransferase increased, aspartate aminotransferase increased, lipase increased, neutropenia/ neutrophil count decreased, and thrombocytopenia/platelet count decreased.

The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea. Grade 3 or 4 laboratory abnormalities (≥ 10%) were neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia and thrombocytopenia. Table 9 summarizes the adverse reactions in POSEIDON.

Table 9. summarizes the laboratory abnormalities in POSEIDON. Table 10. Select Laboratory Abnormalities (≥ 10%) That Worsened from Baseline in Patients with NSCLC Who Received Small Cell Lung Cancer Limited Stage Small Cell Lung Cancer – ADRIATIC The safety of IMFINZI as a single agent in patients with LS-SCLC without disease progression following completion of concurrent platinum-based chemoradiotherapy (60-66 Gy once daily over 6 weeks or 45 Gy twice daily over 3 weeks) within 42 days prior to initiation of study drug, was evaluated in the ADRIATIC study, a multicenter, randomized, double-blind, placebo-controlled study.

The median duration of exposure to IMFINZI was 9.2 months (range: 0.92 to 25) in the IMFINZI arm. 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).

Adverse reactions which resulted in permanent discontinuation of IMFINZI in ≥ 1% of patients included pneumonitis or radiation pneumonitis (9%) and pneumonia (1.5%). Dosage interruptions of IMFINZI due to an adverse reaction occurred in 35% of patients. Adverse reactions which required dosage interruption in ≥ 5% of patients included pneumonitis or radiation pneumonitis (17%).

The most common adverse reactions occurring in ≥ 20% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (38%), and fatigue (21%). Table 11 summarizes the adverse reactions that occurred in patients treated with IMFINZI in the ADRIATIC study. Table 11.

Adverse Reactions (≥ 10%) in Patients with LS-SCLC Who Received summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with IMFINZI. Table 12. Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with LS-SCLC Who Received Extensive Stage Small Cell Lung Cancer – CASPIAN The safety of IMFINZI in combination with etoposide and either carboplatin or cisplatin in previously untreated ES-SCLC was evaluated in CASPIAN, a randomized, open-label, multicenter, active-controlled study.

These include pneumonitis, hepatotoxicity, neurotoxicity, sepsis, diabetic ketoacidosis and pancytopenia (1 patient each). The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia plus chemotherapy. These include pancytopenia, sepsis, septic shock, pulmonary artery thrombosis, pulmonary embolism, and hepatitis (1 patient each) and sudden death (2 patients).

The most common adverse reactions (occurring in ≥ 20% of patients) were nausea, fatigue/asthenia and alopecia. Table 14. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% The frequency cut off is based on any grade change from baseline. of Patients in the CASPIAN Study IMFINZI with Etoposide and either Carboplatin or Cisplatin Etoposide and either Carboplatin or Cisplatin Laboratory Abnormality Grade Graded according to NCI CTCAE version 4.03. 3 or 4 (%) Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: Biliary Tract Cancer Locally Advanced or Metastatic BTC - TOPAZ-1 The safety of IMFINZI in combination with gemcitabine and cisplatin in locally advanced or metastatic BTC was evaluated in TOPAZ-1, a randomized, double-blind, placebo-controlled, multicenter study.

A total of 338 patients received IMFINZI 1,500 mg in combination with gemcitabine and cisplatin every 3 weeks up to 8 cycles followed by IMFINZI 1,500 mg every 4 weeks until disease progression or unacceptable toxicity.Patients with active or prior documented autoimmune or inflammatory disorders, HIV infection or other active infections, including tuberculosis or hepatitis C were ineligible. The most frequently reported events resulting in discontinuation were sepsis (3 patients) and ischemic stroke (2 patients). The remaining events were dispersed across system organ classes and reported in 1 patient each.

The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients) and upper gastrointestinal hemorrhage (2 patients). Table 15 summarizes the adverse reactions that occurred in patients treated with summarizes the laboratory abnormalities in patients treated with IMFINZI plus chemotherapy.

Table 16. Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% The frequency cut off is based on any grade change from baseline. of Patients in the TOPAZ-1 Study Hepatocellular Carcinoma Unresectable HCC - HIMALAYA The safety of IMFINZI in combination with tremelimumab-actl was evaluated in a total of 388 patients with uHCC in HIMALAYA, a randomized, open-label, multicenter study. Patients received IMFINZI 1,500 mg administered as a single intravenous infusion in combination with tremelimumab-actl 300 mg on the same day, followed by IMFINZI every 4 weeks or sorafenib 400 mg given orally twice daily.

Serious adverse reactions occurred in 41% of patients who received IMFINZI in combination with tremelimumab-actl. Serious adverse reactions in > 1% of patients included hemorrhage ( %). The most common adverse reactions (occurring in ≥ 20% of patients) were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain.

Table 17 summarizes the adverse reactions that occurred in patients treated with IMFINZI in combination with tremelimumab-actl in the HIMALAYA study. Table summarizes the laboratory abnormalities that occurred in patients treated with IMFINZI in combination with tremelimumab-actl in the HIMALAYA study. Table 18.

Laboratory Abnormalities Worsening from Baseline Occurring in ≥ Endometrial Cancer Advanced or Recurrent dMMR Endometrial Cancer – DUO-E The safety of IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent was evaluated in 44 patients with dMMR advanced or recurrent endometrial cancer in DUO-E, a randomized, double-blind, placebo-controlled trial. The median duration of exposure to IMFINZI with carboplatin and paclitaxel was 14.8 months (range: 0.7 to 31.7). 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%). The adverse reaction which resulted in permanent discontinuation of IMFINZI (≥ 4%) was rash (4.5%). Dosage interruptions of IMFINZI due to adverse reactions occurred in 52% of patients.

The most common adverse reactions (≥ 20%), including laboratory abnormalities, were peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, decreased magnesium, increased ALT, increased AST, diarrhea, vomiting, cough, decreased potassium, dyspnea, headache, and increased alkaline phosphatase. Tables 19 and 20 summarize adverse reactions and laboratory abnormalities in DUO-E, respectively. Table 0 Clinically relevant adverse reactions in < 10% of patients who received IMFINZI with carboplatin and paclitaxel included autoimmune hemolytic anemia, colitis, immune-mediated thyroiditis, infusion related reaction, interstitial lung disease, myositis, pneumonitis, pulmonary embolism, and sepsis.

Table 20 summarizes the laboratory abnormalities that occurred in patients treated with IMFINZI with carboplatin and paclitaxel followed by IMFINZI as a single agent. Table 20. Select Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 0 Non-Muscle-Invasive Bladder Cancer (NMIBC) BCG-Naïve, High-Risk NMIBC – POTOMAC The safety of IMFINZI in combination with intravesical BCG induction and maintenance treatment was evaluated in POTOMAC, a randomized, open-label, multicenter study.

Patients received IMFINZI in combination with BCG induction and maintenance treatment (n=336) or BCG induction and maintenance treatment alone (n=339). The median duration of exposure to IMFINZI was 52 weeks (range: 4 to 89 weeks). Serious adverse reactions occurred in 32% of patients who received IMFINZI with BCG.

The most common (≥ 1%) serious adverse reactions were urinary tract infection of patients. Adverse reactions which required dosage interruptions of IMFINZI (≥ 1%) were increased lipase (3%), rash ( %) adverse reactions, including laboratory abnormalities were increased glucose, increased AST, increased lipase, increased ALT, increased GGT, urinary tract infection, increased potassium, dysuria, decreased hemoglobin, hematuria, increased serum creatinine, musculoskeletal pain, decreased lymphocytes, urinary frequency, decreased sodium, fatigue, rash, and pyrexia. Table 21 summarizes the adverse reactions that occurred in patients treated with IMFINZI in combination with BCG induction and maintenance treatment.

Table 22 summarizes the laboratory abnormalities that occurred in patients treated with IMFINZI in combination with BCG induction and maintenance in the POTOMAC study. Table 22. Select Laboratory Abnormalities Worsening from Baseline Occurring in ≥ 20% The frequency cut off is based on any grade change from baseline. of Patients Who Received Muscle Invasive Bladder Cancer (MIBC) Neoadjuvant and adjuvant treatment of MIBC – NIAGARA The safety of IMFINZI in combination with neoadjuvant gemcitabine and cisplatin followed by surgery and continued IMFINZI treatment as adjuvant, single-agent therapy was evaluated in NIAGARA, a randomized, open-label, multicenter trial.

Table 24. Select Laboratory Abnormalities That Worsened from Baseline in ≥ in combination with chemotherapy as neoadjuvant treatment in the IMFINZI treatment arm, and 526 patients received at least 1 dose of chemotherapy as neoadjuvant treatment in the chemotherapy treatment arm. In the neoadjuvant phase, serious adverse reactions occurred in 24% of patients who received IMFINZI in combination with chemotherapy; the most frequent (≥ 1%) serious adverse reactions were pulmonary embolism ( %).

One fatal adverse reaction of pneumonia was reported in 1 (0.2%) patient in the post-surgery phase before adjuvant treatment started. Permanent discontinuation of IMFINZI due to an adverse reaction in the neoadjuvant phase occurred in 9% of patients while receiving IMFINZI in combination with chemotherapy. The most frequent (≥ 0.5%) adverse reactions that led to permanent discontinuation of 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. Of the 469 patients in the IMFINZI treatment arm who underwent radical cystectomy, 4 (0.8%) patients experienced delay of surgery (defined as occurring more than 56 days after the last dose of neoadjuvant treatment) due to adverse reactions. Adjuvant Phase of NIAGARA A total of 383 patients (72%) in the IMFINZI treatment arm received at least 1 dose of adjuvant treatment.

Gastric or Gastroesophageal Junction Adenocarcinoma (GC/GEJC) Neoadjuvant and Adjuvant Treatment of Resectable GC/GEJC – MATTERHORN The safety of IMFINZI with FLOT as neoadjuvant and adjuvant treatment, followed by single-agent IMFINZI, was evaluated in MATTERHORN, a randomized, double-blind, placebo-controlled, multicenter study of patients with resectable GC/GEJC (Stage II to Stage IVA ). Table 26: Laboratory Abnormalities (> 20%) That Worsened from Baseline in Patients with Disease Who Received summarizes safety profile by Phase of treatment. Table during the neoadjuvant phase, and pneumonia (2.5%) in the adjuvant phase.

Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, IMFINZI can cause fetal harm when administered to a pregnant woman. There are no available data on the use of IMFINZI in pregnant women. In animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at the clinical dose of 10 mg/kg based on area under the curve (AUC), resulted in an increase in premature delivery, fetal loss, and premature neonatal death ( see Data ).

Human immunoglobulin G1 (IgG1) is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing fetus. Apprise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Data Animal Data As reported in the literature, the PD-1/PD-L1 pathway plays a central role in preserving pregnancy by maintaining maternal immune tolerance to the fetus. In mouse allogeneic pregnancy models, disruption of PD-L1 signaling was shown to result in an increase in fetal loss. The effects of durvalumab on prenatal and postnatal development were evaluated in reproduction studies in cynomolgus monkeys.

Administration of durvalumab resulted in premature delivery, fetal loss (abortion and stillbirth), and increase in neonatal deaths. Durvalumab was detected in infant serum on postpartum Day 1, indicating the presence of placental transfer of durvalumab. Based on its mechanism of action, fetal exposure to durvalumab may increase the risk of developing immune-mediated disorders or altering the normal immune response and immune-mediated disorders have been reported in PD-1 knockout mice.

Pediatric Use The safety and effectiveness of IMFINZI have not been established in pediatric patients. Safety and efficacy were assessed but not established in a multi-center, open-label study (NCT03837899) in 45 pediatric patients aged 1 to < 17 years with advanced solid tumors. All 45 patients received at least a single dose of IMFINZI, and 41 patients received IMFINZI in combination with tremelimumab-actl.

No new safety signals were observed in pediatric patients in this study. Durvalumab systemic exposure in pediatric patients weighing ≥ 35 kg was within the range of values previously observed in adults given the same weight-based dose, whereas the systemic exposure in pediatric patients weighing < 35 kg was lower than that observed in adults.