Renal cell carcinoma (RCC) - combination treatment with ipilimumab

Active Ingredient: Nivolumab

Indication for Nivolumab

Population group: only adults (18 years old or older)
Therapeutic intent: Curative procedure

Nivolumab in combination with ipilimumab is indicated for the first-line treatment of adult patients with intermediate/poor-risk advanced renal cell carcinoma.

For this indication, competent medicine agencies globally authorize below treatments:

3 mg/kg every 3 weeks for the first 4 doses and thereafter 240 mg every 2 weeks or at 480 mg every 4 weeks

For:

Dosage regimens

Regimen A

Intravenous, 3 milligrams nivolumab per kilogram of body weight, once every 3 weeks, 4 doses in total, over the duration of 12 weeks. Afterwards, intravenous, 240 milligrams nivolumab, once every 2 weeks.

Regimen B

Intravenous, 3 milligrams nivolumab per kilogram of body weight, once every 3 weeks, 4 doses in total, over the duration of 15 weeks. Afterwards, intravenous, 480 milligrams nivolumab, once every 4 weeks.

Detailed description

The recommended dose is 3 mg/kg nivolumab in combination with 1 mg/kg ipilimumab administered intravenously every 3 weeks for the first 4 doses. This is then followed by a second phase in which nivolumab monotherapy is administered intravenously at either 240 mg every 2 weeks or at 480 mg every 4 weeks, as presented in the table below. For the monotherapy phase, the first dose of nivolumab should be administered;

  • 3 weeks after the last dose of the combination of nivolumab and ipilimumab if using 240 mg every 2 weeks; or
  • 6 weeks after the last dose of the combination of nivolumab and ipilimumab if using 480 mg every 4 weeks.

Duration of treatment

Treatment with nivolumab, either as a monotherapy or in combination with 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).

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.

Dose escalation or reduction is not recommended. Dosing delay or discontinuation may be required based on individual safety and tolerability.

Nivolumab 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 nivolumab is administered intravenously 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 intravenous combination treatment or nivolumab monotherapy administered intravenously or subcutaneously could be resumed based on the evaluation of the individual patient.

Dosage considerations

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

600 mg every 2 weeks or 1200 mg every 4 weeks after intravenously administered nivolumab with ipilimumab for 4 cycles

For:

Dosage regimens

Regimen A

Intravenous, 3 milligrams nivolumab per kilogram of body weight, once every 3 weeks, 4 doses in total, over the duration of 15 weeks. Afterwards, subcutaneous, 600 milligrams nivolumab, once every 2 weeks.

Regimen B

Intravenous, 1 milligrams nivolumab per kilogram of body weight, once every 3 weeks, 4 doses in total, over the duration of 18 weeks. Afterwards, subcutaneous, 1,200 milligrams nivolumab, once every 4 weeks.

Detailed description

Recommended doses and infusion times for nivolumab solution for infusion in combination with ipilimumab followed by OPDIVO solution for injection monotherapy for RCC:

 Combination phase
OPDIVO solution for
infusion, intravenously
(IV) and ipilimumab, for
4 dosing cycles
Monotherapy phase
OPDIVO solution for injection, subcutaneously (SC)
Nivolumab3 mg/kg every 3 weeks over
30 minutes
600 mg every 2 weeks or 1200 mg every 4 weeks

The first dose should be administered:
• 3 weeks after the last dose of the combination of IV
nivolumab and ipilimumab if using 600 mg every
2 weeks; or
• 6 weeks after the last dose of the combination of IV
nivolumab and ipilimumab if using 1200 mg every
4 weeks.
Ipilimumab1 mg/kg every 3 weeks over
30 minutes
-

Duration of treatment

Treatment with nivolumab, either as a monotherapy or in combination with 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).

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.

Dose escalation or reduction is not recommended. Dosing delay or discontinuation may be required based on individual safety and tolerability.

Nivolumab 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 nivolumab is administered intravenously 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 intravenous combination treatment or nivolumab monotherapy administered intravenously or subcutaneously could be resumed based on the evaluation of the individual patient.

Dosage considerations

Administer the full contents of the syringe of nivolumab solution for injection into the subcutaneous tissue of the abdomen or thigh over a period of 3 to 5 minutes. The dose should not be split between two syringes or between two sites of administration. Alternate injection sites for successive injections. Do not inject into areas where the skin is tender, red, or bruised, or areas where there are scars or moles. If the administration of nivolumab solution for injection is interrupted, it can be resumed at the same site, or at an alternate site.

During the treatment course with nivolumab solution for injection, other medicinal products for subcutaneous administration should preferably be injected at different sites.

Active ingredient

Nivolumab

Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody (HuMAb), which binds to the programmed death-1 (PD-1) receptor and blocks its interaction with PD-L1 and PD-L2. Nivolumab potentiates T-cell responses, including anti-tumour responses, through blockade of PD-1 binding to PD-L1 and PD-L2 ligands. In syngeneic mouse models, blocking PD-1 activity resulted in decreased tumour growth.

Read more about Nivolumab

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