Imfinzi

HOS-098703 · has-adverse-reaction-information · PDF-Seite 15

Summary of the safety profile IMFINZI as monotherapy The safety of IMFINZI as monotherapy is based on pooled data in 4 642 patients across multiple tumour types. IMFINZI was administered at a dose of 10 mg/kg every 2 weeks, 20 mg/kg every 4 weeks or 1 500 mg every 4 weeks. The most common (> 10%) adverse reactions were cough/productive cough (18.1%), diarrhoea (15.1%), rash (15.0%), arthralgia (12.4%), pyrexia (12.5%), abdominal pain (11.8%), upper respiratory tract infections (11.8%), pruritus (11.1%), and hypothyroidism (11.6%). The most common (> 2%) NCI CTCAE Grade ≥ 3 adverse reactions were pneumonia (3.4%) and aspartate aminotransferase increased/alanine aminotransferase increased (2.5%). IMFINZI was discontinued due to adverse reactions in 3.9% of patients. The most common adverse reactions leading to treatment discontinuation were pneumonitis (1.1%) and pneumonia (0.8%). IMFINZI was delayed or interrupted due to adverse reactions in 13.1% of patients. The most common adverse reactions leading to dose delay or interruption were pneumonia (2.3%) and aspartate aminotransferase increased/alanine aminotransferase increased (2.0%). The safety of IMFINZI as monotherapy in patients treated for HCC is based on data in 492 patients and was consistent with the overall safety profile in the IMFINZI monotherapy pool (N=4 642). The most common (> 10%) adverse reactions were AST increased/ALT increased (20.3%), abdominal pain (17.9%), diarrhoea (15.9%), pruritus (15.4%), and rash (15.2%). The most common (> 2%) Grade ≥ 3 adverse reactions were AST increased/ALT increased (8.1%) and abdominal pain (2.2%). IMFINZI was discontinued due to adverse reactions in 3.7% of patients. The most common adverse reactions leading to treatment discontinuation were AST increased/ALT increased (0.8%) and hepatitis (0.6%). IMFINZI was delayed or interrupted due to adverse reactions in 11.6% of patients. The most common adverse reaction leading to dose delay or interruption was AST increased/ALT increased (5.9%). IMFINZI in combination with chemotherapy 15 The safety of IMFINZI in combination with chemotherapy is based on pooled data in 2 244 patients from 6 studies (TOPAZ-1, CASPIAN, DUO-E, AEGEAN, NIAGARA and MATTERHORN). The most common (> 10%) adverse reactions were neutropenia (44.6%), nausea (42.4%), fatigue (41.2%), anaemia (37.4%), diarrhoea (27.5%), constipation (26.7%), decreased appetite (24.0%), alopecia (22.0%),

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HOS-098699 · has-contraindication-information · PDF-Seite 10

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

HOS-098698 · has-indication-information · PDF-Seite 2

Non-Small Cell Lung Cancer (NSCLC) IMFINZI in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by IMFINZI as monotherapy as adjuvant treatment, is indicated for the treatment of adults with resectable NSCLC at high risk of recurrence and no EGFR mutations or ALK rearrangements (for selection criteria, see section 5.1). IMFINZI as monotherapy is indicated for the treatment of locally advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on ≥ 1% of tumour cells and whose disease has not progressed following platinum-based chemoradiation therapy (see section 5.1). IMFINZI in combination with tremelimumab and platinum-based chemotherapy is indicated for the first-line treatment of adults with metastatic NSCLC with no sensitising EGFR mutations or ALK positive mutations. Small Cell Lung Cancer (SCLC) IMFINZI as monotherapy is indicated for the treatment of adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiation therapy. IMFINZI in combination with etoposide and either carboplatin or cisplatin is indicated for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC). Biliary Tract Cancer (BTC) IMFINZI in combination with gemcitabine and cisplatin is indicated for the first-line treatment of adults with unresectable or metastatic biliary tract cancer (BTC). 2 Hepatocellular Carcinoma (HCC) IMFINZI as monotherapy is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC). IMFINZI in combination with tremelimumab is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC). Endometrial Cancer IMFINZI in combination with carboplatin and paclitaxel is indicated for the first-line treatment of adults with primary advanced or recurrent endometrial cancer who are candidates for systemic therapy, followed by maintenance treatment with: • IMFINZI as monotherapy in endometrial cancer that is mismatch repair deficient (dMMR) • IMFINZI in combination with olaparib in endometrial cancer that is mismatch repair proficient (pMMR). Muscle Invasive Bladder Cancer (MIBC) IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by IMFINZI as monotherapy adjuvant treatment after radical cyste

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HOS-098701 · has-interaction-information · PDF-Seite 14

The use of systemic corticosteroids or immunosuppressants before starting durvalumab, except physiological dose of systemic corticosteroids (≤ 10 mg/day prednisone or equivalent), is not recommended because of their potential interference with the pharmacodynamic activity and efficacy of durvalumab. However, systemic corticosteroids or other immunosuppressants can be used after starting durvalumab to treat immune-related adverse reactions (see section 4.4). No formal pharmacokinetic (PK) drug-drug interaction studies have been conducted with durvalumab. Since the primary elimination pathways of durvalumab are protein catabolism via reticuloendothelial system or target-mediated disposition, no metabolic drug-drug interactions are expected. PK drug-drug interactions of durvalumab in combination with other therapeutic agents were compared with durvalumab in the CASPIAN, POSEIDON, HIMALAYA, and DUO-E studies; no clinically meaningful PK drug-drug interactions were identified.

HOS-098702 · has-pregnancy-information · PDF-Seite 14

Women of childbearing potential/Contraception Women of childbearing potential should use effective contraception during treatment with durvalumab and for at least 3 months after the last dose of durvalumab. Pregnancy There are no data on the use of durvalumab in pregnant women. Based on its mechanism of action, durvalumab has the potential to impact maintenance of pregnancy, and in a mouse allogeneic pregnancy model, disruption of PD-L1 signaling was shown to result in an increase in foetal loss. Animal studies with durvalumab are not indicative of reproductive toxicity (see section 5.3). Human IgG1 is known to cross the placental barrier and placental transfer of durvalumab was confirmed in 14 animal studies. Durvalumab may cause foetal harm when administered to a pregnant woman and is not recommended during pregnancy and in women of childbearing potential not using effective contraception during treatment and for at least 3 months after the last dose. Breast-feeding It is unknown whether durvalumab is secreted in human breast milk. Available toxicological data in cynomolgus monkeys have shown low levels of durvalumab in breast milk on day 28 after birth (see section 5.3). In humans, antibodies may be transferred to breast milk, but the potential for absorption and harm to the newborn is unknown. However, a potential risk to the breast-fed child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue or abstain from durvalumab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no data on the potential effects of durvalumab on fertility in humans or animals.

HOS-098700 · has-warning-information · PDF-Seite 10

Refer to section 4.2, Table 2 for recommended treatment modifications. For suspected immune-mediated adverse reactions, adequate evaluation should be performed to confirm etiology or exclude alternate etiologies. Based on the severity of the adverse reaction, IMFINZI or IMFINZI in combination with tremelimumab should be withheld or permanently 10 discontinued. Treatment with corticosteroids or endocrine therapy should be initiated. For events requiring corticosteroid therapy, and upon improvement to ≤ Grade 1, corticosteroid taper should be initiated and continued over at least 1 month. Consider increasing dose of corticosteroids and/or using additional systemic immunosuppressants if there is worsening or no improvement. Traceability In order to improve the traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded. Immune-mediated pneumonitis Immune-mediated pneumonitis or interstitial lung disease, defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving IMFINZI, IMFINZI in combination with tremelimumab, IMFINZI in combination with platinum-based chemotherapy followed by IMFINZI in combination with olaparib, or in combination with chemotherapy (see section 4.8). For Grade 2 events, an initial dose of 1-2 mg/kg/day prednisone or equivalent should be initiated followed by a taper. For Grade 3 or 4 events, an initial dose of 2- 4 mg/kg/day methylprednisolone or equivalent should be initiated followed by a taper. Pneumonitis and radiation pneumonitis Radiation pneumonitis is frequently observed in patients receiving radiation therapy to the lung and the clinical presentation of pneumonitis and radiation pneumonitis is very similar. In the PACIFIC Study, in patients who had completed treatment with at least 2 cycles of concurrent chemoradiation within 1 to 42 days prior to initiation of study treatment, pneumonitis or radiation pneumonitis occurred in 161 (33.9%) patients in the IMFINZI-treated group and 58 (24.8%) in the placebo group, including Grade 3 (3.4% vs. 3.0%) and Grade 5 (1.1% vs. 1.7%). In the AEGEAN study, in patients who have received post-operative radiotherapy (PORT), pneumonitis and radiation pneumonitis occurred in 10 (33.3%) patients in the IMFINZI-treated group and 3 (11.1%) patients in the placebo group, including 2 patients with maximum Gra

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