OPDIVO CONCENTRATE FOR SOLUTION FOR INFUSION 10 MG/ML [SIN14975P]

Product Info

OPDIVO CONCENTRATE FOR SOLUTION FOR INFUSION 10 MG/ML

[SIN14975P]

4.1 Therapeutic indications

Melanoma

OPDIVO as monotherapy or in combination with ipilimumab is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults and adolescents 12 years of age and older.

Relative to nivolumab monotherapy, an increase in progression-free survival (PFS) for the combination of nivolumab with ipilimumab is established only in patients with low tumour PD-L1 expression (see sections 4.4 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Adjuvant treatment of melanoma

OPDIVO as monotherapy is indicated for the adjuvant treatment of adults and adolescents 12 years of age and older with Stage IIB or IIC melanoma, or melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Non-Small Cell Lung Cancer (NSCLC)

OPDIVO, in combination with ipilimumab and 2 cycles of platinum-based chemotherapy, is indicated for the first-line treatment of metastatic or recurrent NSCLC in adult patients with no EGFR or ALK genomic tumor mutations.

OPDIVO as monotherapy is indicated for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy in adults.

Neoadjuvant treatment of NSCLC

OPDIVO, in combination with platinum-doublet chemotherapy, is indicated for the neoadjuvant treatment of adult patients with resectable (tumours ≥4 cm or node positive) NSCLC.

Malignant pleural mesothelioma (MPM)

OPDIVO, in combination with ipilimumab, is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma.

Renal Cell Carcinoma (RCC)

OPDIVO, in combination with ipilimumab, is indicated for the treatment of patients with intermediate or poor-risk, previously untreated advanced renal cell carcinoma.

OPDIVO as monotherapy is indicated for the treatment of advanced renal cell carcinoma after prior therapy in adults.

OPDIVO in combination with cabozantinib is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Classical Hodgkin Lymphoma (cHL)

OPDIVO as monotherapy is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant (ASCT) and treatment with brentuximab vedotin (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Squamous Cell Cancer of the Head and Neck (SCCHN)

OPDIVO as monotherapy is indicated for the treatment of recurrent or metastatic squamous cell cancer of the head and neck in adults progressing on or after platinum-based therapy in adults (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Gastric/ Gastroesophageal Junction (GEJ) Cancer

OPDIVO as monotherapy is indicated for the treatment of adult patients with unresectable locally advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma after two or more prior systemic therapies.

Oesophageal Squamous Cell Carcinoma (OSCC)

OPDIVO in combination with ipilimumab is indicated for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥1%.

OPDIVO in combination with fluoropyrimidine- and platinum-based combination chemotherapy is indicated for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥1%.

OPDIVO as monotherapy is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based combination chemotherapy.

Gastric Cancer, Gastroesophageal Junction (GEJ) Cancer or Oesophageal Adenocarcinoma

OPDIVO, in combination with fluoropyrimidine- and platinum-based chemotherapy, is indicated for the treatment of patients with unresectable HER2 negative advanced or metastatic gastric cancer, gastroesophageal junction cancer, or oesophageal adenocarcinoma (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Adjuvant treatment of oesophageal or gastroesophageal junction cancer (OC or GEJC)

OPDIVO as monotherapy is indicated for the adjuvant treatment of completely resected oesophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).

Urothelial carcinoma

OPDIVO, in combination with cisplatin and gemcitabine, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma.

OPDIVO as monotherapy is indicated for the adjuvant treatment of adults with muscle invasive urothelial carcinoma (MIUC) with tumor cell PD-L1 expression ≥1% who are at high risk of recurrence after undergoing radical resection of MIUC.

4.2 Posology and method of administration

Treatment must be initiated and supervised by physicians experienced in the treatment of cancer.

Posology

OPDIVO as monotherapy
The recommended dose of OPDIVO is 3 mg/kg administered intravenously over 30–60 minutes every 2 weeks.

Melanoma (advanced or adjuvant treatment)

Oesophageal Squamous Cell Carcinoma (OSCC)

The recommended dose of OPDIVO is 240 mg administered intravenously over 30–60 minutes every 2 weeks.

Adjuvant treatment of oesophageal or gastroesophageal junction cancer (OC or GEJC)

The recommended dose of OPDIVO is 240 mg administered intravenously over 30–60 minutes every 2 weeks, or 480 mg administered intravenously over 30–60 minutes every 4 weeks.

Muscle invasive urothelial carcinoma (MIUC) adjuvant treatment
The recommended dose of OPDIVO is 240 mg administered intravenously over 30–60 minutes every 2 weeks, or 480 mg administered intravenously over 30–60 minutes every 4 weeks.

OPDIVO in combination with ipilimumab

Melanoma
The recommended dose is 1 mg/kg nivolumab administered as an intravenous infusion over 30–60 minutes every 3 weeks for the first 4 doses in combination with 3 mg/kg ipilimumab administered intravenously over 30–90 minutes.

This is then followed by a second phase in which 3 mg/kg nivolumab is administered as an intravenous infusion over 30–60 minutes every 2 weeks.

Non-Small Cell Lung Cancer (NSCLC)
The recommended dose is 360 mg nivolumab administered as an intravenous infusion every 3 weeks in combination with 1 mg/kg ipilimumab administered as an intravenous infusion every 6 weeks, and platinum chemotherapy administered every 3 weeks. After completion of 2 cycles of chemotherapy, treatment is continued with 360 mg nivolumab administered as an intravenous infusion every 3 weeks in combination with 1 mg/kg ipilimumab every 6 weeks. Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Malignant pleural mesothelioma (MPM)
The recommended dose of nivolumab is either 3 mg/kg every 2 weeks or 360 mg every 3 weeks administered as an intravenous infusion over 30–60 minutes in combination with 1 mg/kg ipilimumab administered as an intravenous infusion over 30 minutes every 6 weeks. Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Renal Cell Carcinoma (RCC)
The recommended dose is 3 mg/kg nivolumab administered as an intravenous infusion over 30–60 minutes every 3 weeks for the first 4 doses in combination with 1 mg/kg ipilimumab administered intravenously over 30 minutes.

This is then followed by a second phase in which 3 mg/kg nivolumab is administered as an intravenous infusion over 30–60 minutes every 2 weeks. The first dose of nivolumab monotherapy should be administered 3 weeks following the last dose of the combination of nivolumab and ipilimumab.

Oesophageal squamous cell carcinoma
The recommended dose is either 3 mg/kg nivolumab every 2 weeks or 360 mg nivolumab every 3 weeks administered intravenously over 30-60 minutes in combination with 1 mg/kg ipilimumab administered intravenously over 30 minutes every 6 weeks. Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

OPDIVO in combination with cabozantinib

Renal Cell Carcinoma (RCC)
The recommended dose is nivolumab administered intravenously at either 240 mg every 2 weeks over 30 minutes or 480 mg every 4 weeks over 60 minutes in combination with 40 mg cabozantinib administered orally every day.

OPDIVO in combination with chemotherapy

Neoadjuvant treatment of non-small cell lung cancer
The recommended dose is 360 mg nivolumab administered intravenously over 30–60 minutes in combination with platinum-based chemotherapy every 3 weeks for 3 cycles (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Gastric cancer, gastroesophageal junction cancer and oesophageal adenocarcinoma
The recommended dose is 360 mg nivolumab administered intravenously over 30–60 minutes in combination with fluoropyrimidine- and platinum-based chemotherapy every 3 weeks or 240 mg nivolumab administered intravenously over 30–60 minutes in combination with fluoropyrimidine- and platinum-based chemotherapy every 2 weeks (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Treatment is recommended until disease progression or unacceptable toxicity. The maximum treatment duration for OPDIVO is 24 months.

Oesophageal squamous cell carcinoma
The recommended dose of nivolumab is 240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously over 30–60 minutes in combination with fluoropyrimidine- and platinum-based chemotherapy (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Treatment with nivolumab is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

First-line treatment of unresectable or metastatic urothelial carcinoma
The recommended dose of nivolumab is 360 mg administered intravenously over 30-60 minutes in combination with cisplatin and gemcitabine every 3 weeks for up to 6 cycles followed by nivolumab monotherapy administered intravenously at either 240 mg every 2 weeks over 30–60 minutes or at 480 mg every 4 weeks over 30–60 minutes. Treatment with nivolumab is recommended until disease progression, unacceptable toxicity, or up to 24 months from first dose, whichever comes first.

Duration of treatment
Treatment with OPDIVO, either as monotherapy or in combination with ipilimumab or other therapeutic agents, should be continued as long as clinical benefit is observed or until treatment is no longer tolerated by the patient (and up to maximum duration of therapy if specified for an indication).

For adjuvant therapy, the maximum treatment duration with OPDIVO is 12 months.

Atypical responses (i.e., an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. It is recommended to continue treatment with nivolumab or nivolumab in combination with ipilimumab for clinically stable patients with initial evidence of disease progression until disease progression is confirmed.

For OPDIVO in combination with cabozantinib, nivolumab should be continued until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Cabozantinib should be continued until disease progression or unacceptable toxicity. Refer to the product insert for cabozantinib.

Dose escalation or reduction is not recommended for OPDIVO as monotherapy or in combination with other therapeutic agents. Dosing delay or discontinuation may be required based on individual safety and tolerability. Guidelines for permanent discontinuation or withholding of doses are described in Table 1. Detailed guidelines for the management of immune-related adverse reactions are described in section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information. When nivolumab is administered in combination with other therapeutic agents, refer to the product insert of these other combination therapeutic agents regarding dosing.

OPDIVO as monotherapy or in combination with other therapeutic agents should be permanently discontinued for:

• Grade 4 or recurrent Grade 3 adverse reactions;

• Persistent Grade 2 or 3 adverse reactions despite management.

When OPDIVO is administered in combination with ipilimumab, if either agent is withheld, the other agent should also be withheld. If dosing is resumed after a delay, either the combination treatment or OPDIVO monotherapy could be resumed based on the evaluation of the individual patient.

When OPDIVO is administered in combination with chemotherapy, refer to the product information of the other combination therapy agents regarding dosing. If any agents are withheld, the other agents may be continued. If dosing is resumed after a delay, either the combination treatment, OPDIVO monotherapy or chemotherapy alone could be resumed based on the evaluation of the individual patient.

OPDIVO in combination with cabozantinib in RCC
When nivolumab is used in combination with cabozantinib, the above treatment modifications in Table 1 also apply to the nivolumab component. In addition, for liver enzyme elevations, in patients with RCC being treated with nivolumab in combination with cabozantinib:

• If ALT or AST > 3 times ULN but ≤ 10 times ULN without concurrent total bilirubin ≥ 2 times ULN, both nivolumab and cabozantinib should be withheld until these adverse reactions recover to Grades 0–1. Corticosteroid therapy may be considered. Rechallenge with a single medicine or rechallenge with both medicines after recovery may be considered. If rechallenging with cabozantinib, refer to cabozantinib product insert.

• If ALT or AST > 10 times ULN or > 3 times ULN with concurrent total bilirubin ≥ 2 times ULN, both nivolumab and cabozantinib should be permanently discontinued and corticosteroid therapy may be considered.

For RCC patients treated with nivolumab in combination with cabozantinib, refer to the product insert regarding treatment modifications of cabozantinib.

Special populations

Paediatric population
The safety and efficacy of OPDIVO in children below 18 years of age have not been established, except in adolescents 12 years of age and older with melanoma.

Elderly
No dose adjustment is required for elderly patients (≥ 65 years) (see sections 5.1 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Renal impairment
Based on the population pharmacokinetic (PK) results, no dose adjustment is required in patients with mild or moderate renal impairment (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Data from patients with severe renal impairment are too limited to draw conclusions on this population.

Hepatic impairment
Based on the population PK results, no dose adjustment is required in patients with mild hepatic impairment (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Data from patients with moderate (total bilirubin > 1.5 x to 3 x the upper limits of normal [ULN] and any AST) or severe (total bilirubin >3 x ULN and any AST) hepatic impairment are too limited to draw conclusions on these populations.

Method of administration

OPDIVO is for intravenous use only. It is to be administered as an intravenous infusion over a period of 30– 60 minutes. The infusion must be administered through a sterile, non-pyrogenic, low protein binding in-line filter with a pore size of 0.2–1.2 micrometre. Do not coadminister other drugs through the same intravenous line.

OPDIVO must not be administered as an intravenous push or bolus injection.

The total dose of OPDIVO required can be infused directly as a 10 mg/mL solution or can be diluted to as low as 1 mg/mL with sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 50 mg/mL (5%) solution for injection.

When administered in combination with ipilimumab and/or chemotherapy, OPDIVO should be given first followed by ipilimumab (if applicable) and then chemotherapy on the same day. Use separate infusion bags and filters for each infusion.

For instructions on the handling of the medicinal product before administration, see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.