Rybrevant

Treatment with Rybrevant should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. Rybrevant should be administered by a healthcare professional with access to appropriate medical support to manage infusion-related reactions (IRRs) if they occur.

3 Before initiation of Rybrevant therapy, EGFR mutation status in tumour tissue or plasma specimens must be established using a validated test method. If no mutation is detected in a plasma specimen, tumour tissue should be tested if available in sufficient amount and quality due to the potential for false negative results using a plasma-test.

1). Posology Premedications should be administered to reduce the risk of IRRs with Rybrevant (see below “Dose modifications” and “Recommended concomitant medicinal products”). Every 3 weeks The recommended dosages of Rybrevant, when used in combination with carboplatin and pemetrexed, is provided in Table 1 (see below “Infusion rates” and Table 5).

Table 1:

Recommended dosage of Rybrevant every 3 weeks Body weight at baselinea Rybrevant dose Schedule Number of vials Less than 80 kg 1400 mg Weekly (total of 4 doses) from Weeks 1 to 4  Week 1 - split infusion on Day 1 and Day 2  Weeks 2 to 4 - infusion on Day 1 4 1750 mg Every 3 weeks starting at Week 7 onwards 5 Greater than or equal to 80 kg 1750 mg Weekly (total of 4 doses) from Weeks 1 to 4  Week 1 - split infusion on Day 1 and Day 2  Weeks 2 to 4 - infusion on Day 1 5 2100 mg Every 3 weeks starting at Week 7 onwards 6 a Dose adjustments not required for subsequent body weight changes.

When used in combination with carboplatin and pemetrexed, Rybrevant should be administered after carboplatin and pemetrexed in the following order: pemetrexed, carboplatin and then Rybrevant. 1 and the manufacturer’s prescribing information for dosing instructions for carboplatin and pemetrexed.

Every 2 weeks The recommended dosages of Rybrevant monotherapy or in combination with lazertinib is provided in Table 2 (see below “Infusion rates” and Table 6).

Table 2:

Recommended dosage of Rybrevant every 2 weeks Body weight at baselinea Rybrevant dose Schedule Number of 350 mg/7 mL Rybrevant vials Less than 80 kg 1050 mg Weekly (total of 4 doses) from weeks 1 to 4  Week 1 - split infusion on Day 1 and Day 2  Weeks 2 to 4 - infusion on Day 1 3 Every 2 weeks starting at Week 5 onwards Greater than or equal to 80 kg 1400 mg Weekly (total of 4 doses) from Weeks 1 to 4  Week 1 - split infusion on Day 1 and Day 2  Weeks 2 to 4 - infusion on Day 1 4 Every 2 weeks starting at Week 5 onwards a Dose adjustments not required for subsequent body weight changes.

Summary of the safety profile In the dataset of amivantamab as monotherapy (N=380), the most frequent adverse reactions in all grades were rash (76%), infusion-related reactions (67%), nail toxicity (47%), hypoalbuminaemia (31%), oedema (26%), fatigue (26%), stomatitis (24%), nausea (23%), and constipation (23%).

1%). Three percent of patients discontinued Rybrevant due to adverse reactions. 5%). Tabulated list of adverse reactions Table 7 summarises the adverse drug reactions that occurred in patients receiving amivantamab as monotherapy. 10 The data reflects exposure to amivantamab in 380 patients with locally advanced or metastatic non-small cell lung cancer after failure of platinum-based chemotherapy.

Patients received amivantamab 1050 mg (for patients < 80 kg) or 1400 mg (for patients ≥ 80 kg). 7 months). Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000); and not known (frequency cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. 8† Pyrexia 11 0 Injury, poisoning and procedural complications Infusion related reaction Very common 67 2 * Grouped terms † Grade 3 events only Summary of the safety profile In the dataset of amivantamab in combination with carboplatin and pemetrexed (N=301), the most frequent adverse reactions in all grades were rash (83%), neutropenia (57%), nail toxicity (53%), infusion related reactions (51%), fatigue (43%), stomatitis (39%), nausea (43%), thrombocytopenia (40%), constipation (40%), oedema (40%), decreased appetite (33%), hypoalbuminaemia (32%), alanine aminotransferase increased (26%), aspartate aminotransferase increased (23%), vomiting (22%), and hypokalaemia (20%).

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. 8). Prior to initial infusion (Week 1), antihistamines, antipyretics, and glucocorticoids should be administered to reduce the risk of IRRs.

For subsequent doses, antihistamines and antipyretics should be administered. The initial infusion should be administered in split doses on Week 1, Day 1 and 2. Patients should be treated in a setting with appropriate medical support to treat IRRs.

Infusions should be interrupted at the first sign of IRRs of any severity and post-infusion medicinal products should be administered as clinically indicated. Upon resolution of symptoms, the infusion should be resumed at 50% of the previous rate.

2). 8). , dyspnoea, cough, fever). If symptoms develop, treatment with Rybrevant should be interrupted pending investigation of these symptoms. Suspected ILD or ILD-like adverse reactions should be evaluated and appropriate treatment should be initiated as necessary.

2). 8). Consistent with clinical guidelines, patients should receive prophylactic dosing of either a 8 direct acting oral anticoagulant (DOAC) or a low-molecular weight heparin (LMWH). Use of Vitamin K antagonists is not recommended. Signs and symptoms of VTE events should be monitored.

Patients with VTE events should be treated with anticoagulation as clinically indicated. For VTE events associated with clinical instability treatment should be withheld until the patient is clinically stable. Thereafter, both drugs can be resumed at the same dose.

In the event of recurrence despite appropriate anticoagulation, Rybrevant should be discontinued. 2). 8). Patients should be instructed to limit sun exposure during and for 2 months after Rybrevant therapy. Protective clothing and use of broad-spectrum UVA/UVB sunscreen are advisable.

1.