The following adverse reactions are discussed in greater detail in other sections of the labeling.
Immune-Mediated Pneumonitis [see Precautions].
Immune-Mediated Hepatitis [see Precautions].
Immune-Mediated Colitis [see Precautions].
Immune-Mediated Endocrinopathies [see Precautions].
Immune-Mediated Nephritis [see Precautions].
Immune-Mediated Dermatologic Reactions [see Precautions].
Other Immune-Mediated Adverse Reactions [see Precautions].
Infection [see Precautions].
Infusion-Related Reactions [see Precautions].
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 Precautions section reflect exposure to IMFINZI in 1889 patients from the PACIFIC study (a randomized, placebo-controlled study that enrolled 475 patients with Stage III NSCLC), and Study 1108 (an open-label, single-arm, multicohort study that enrolled 191 patients with urothelial carcinoma and 779 patients with various other solid tumors), and an additional open-label, single-arm trial that enrolled 444 patients with metastatic lung cancer, indications for which durvalumab is not approved. Across all studies, IMFINZI was administered at a dose of 10 mg/kg intravenously every 2 weeks. Among the 1889 patients, 38% were exposed for 6 months or more and 18% were exposed for 12 months or more.
The data described in this section reflect exposure to IMFINZI in patients with Stage III NSCLC enrolled in the PACIFIC study.
Non-Small Cell Lung Cancer:
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 [see Pharmacology: Clinical Studies under Actions].
The study population characteristics were: median age of 64 years (range: 23 to 90), 45% age 65 years or older, 70% male, 69% White, 27% Asian, 75% former smoker, 16% current smoker, and 51% had WHO performance status 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 3 summarizes the adverse reactions that occurred in at least 10% of patients treated with IMFINZI. (See Table 3.)
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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 4 summarizes the laboratory abnormalities that occurred in at least 20% of patients treated with IMFINZI. (See Table 4.)
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As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to durvalumab to the incidence of antibodies to other products may be misleading.
Due to the limitations in assay performance, the incidence of antibody development in patients receiving IMFINZI may be underestimated. Of 1570 patients who were treated with IMFINZI 10 mg/kg every 2 weeks and evaluable for the presence of anti-drug antibodies (ADAs), 45 (2.9%) patients tested positive for treatment-emergent ADAs. The development of treatment-emergent ADA against durvalumab appears to have no clinically relevant effect on its pharmacokinetic profile. There are insufficient numbers of patients with ADA to determine whether ADA alters the safety or efficacy of durvalumab.