Nivomab

FDA-Approved and Globally Recognized Indications:

A. Melanoma

• Unresectable or metastatic melanoma as monotherapy or in combination with ipilimumab
• Adjuvant treatment of completely resected Stage III or IV melanoma

B. Non-Small Cell Lung Cancer (NSCLC)

• Metastatic NSCLC after prior platinum-based chemotherapy
• First-line treatment of metastatic NSCLC in combination with ipilimumab, with or without chemotherapy

C. Renal Cell Carcinoma (RCC)

• Previously treated advanced RCC as monotherapy
• First-line treatment in combination with ipilimumab for intermediate- or poor-risk advanced RCC

D. Classical Hodgkin Lymphoma

• Relapsed or refractory classical Hodgkin lymphoma after autologous HSCT and brentuximab vedotin

E. Head and Neck Squamous Cell Carcinoma (HNSCC)

• Recurrent or metastatic HNSCC with disease progression after platinum-based therapy

F. Urothelial Carcinoma

• Advanced or metastatic urothelial carcinoma after progression with platinum-based chemotherapy

G. Esophageal Squamous Cell Carcinoma

• Advanced or metastatic disease following fluoropyrimidine- and platinum-based chemotherapy

H. Hepatocellular Carcinoma (HCC)

• Previously treated with sorafenib

Clinically Accepted Off-label Uses:

• MSI-H/dMMR Colorectal Cancer: In combination with ipilimumab for advanced disease
• Triple-Negative Breast Cancer (TNBC): Under investigation in immunotherapy combinations

Adults:

• Monotherapy: 240 mg IV every 2 weeks or 480 mg IV every 4 weeks
• With Ipilimumab (e.g., for melanoma or RCC):
• 3 mg/kg nivolumab + 1 mg/kg ipilimumab IV every 3 weeks for 4 doses
• Followed by 240 mg nivolumab every 2 weeks or 480 mg every 4 weeks

Melanoma (Adjuvant):

• 240 mg IV every 2 weeks or 480 mg IV every 4 weeks for up to 12 months

Classical Hodgkin Lymphoma (≥12 years):

• 3 mg/kg IV every 2 weeks

Administration Guidelines:

• Administer as IV infusion over 30 minutes
• Do not give as IV push or bolus
• Use sterile, low-protein-binding infusion sets with an in-line filter (0.2 to 1.2 micron)

Elderly:

• No specific dose adjustment; monitor for adverse events

Renal/Hepatic Impairment:

• No dosage adjustment necessary; use with caution and monitor organ function

Duration:

• Until disease progression or unacceptable toxicity
• Up to 2 years in some cancers with durable response

Nivolumab is a fully human IgG4 monoclonal antibody that targets the PD-1 (programmed death-1) receptor on activated T cells. Normally, the interaction of PD-1 with its ligands PD-L1 and PD-L2 downregulates T-cell activity to prevent autoimmunity. Cancer cells exploit this by overexpressing PD-L1, leading to immune evasion. Nivolumab blocks this PD-1/PD-L1 interaction, restoring T-cell activation and proliferation, and thereby enhancing the immune system’s ability to recognize and destroy tumor cells. This mechanism underlies its broad application in multiple solid and hematologic malignancies.

• Absorption: Not applicable (IV only)
• Distribution: Volume of distribution ~8 L
• Bioavailability: 100% (IV route)
• Metabolism: Degraded into small peptides and amino acids via non-specific proteolytic pathways
• Half-life: ~25 days
• Steady State: Reached in ~12 weeks with regular dosing
• Elimination: Primarily via reticuloendothelial system; renal and hepatic function not significant in clearance

• Pregnancy:
  Not assigned (monoclonal antibodies use narrative description).
  Based on its mechanism, nivolumab may cause fetal harm, especially during organogenesis. Animal studies suggest potential embryotoxicity. Use only if benefits outweigh risks. Recommend contraception during treatment and for 5 months post-therapy.
• Lactation:
  Unknown if excreted in human milk. Due to the potential for serious immune-mediated effects in infants, breastfeeding is not recommended during and for at least 5 months after the last dose.

• Primary Class: Immunotherapy – Checkpoint Inhibitor
• Subclass: Anti–PD-1 Human Monoclonal Antibody (IgG4)

• Known hypersensitivity to nivolumab or any excipients
• History of severe immune-mediated adverse reactions to checkpoint inhibitors
• Patients with active autoimmune disease requiring systemic immunosuppressants

• Immune-Related Adverse Events (Potentially Fatal):
• Pneumonitis
• Colitis
• Hepatitis
• Endocrinopathies (e.g., hypothyroidism, adrenal insufficiency, type 1 diabetes)
• Nephritis
• Severe skin reactions (e.g., Stevens-Johnson Syndrome)
• Infusion Reactions:
  Monitor for symptoms (fever, chills, dyspnea); may require premedication if prior reaction occurred.
• Infection Risk:
  Reactivation of latent infections possible; consider screening for TB and hepatitis.
• Organ Transplant Patients:
  Risk of allograft rejection—use only if benefits outweigh risks.
• Clinical Monitoring:
  Regular LFTs, renal function, thyroid function tests, blood glucose, and adrenal function.

Common (≥10%):

• General: Fatigue, pyrexia
• GI: Nausea, decreased appetite, diarrhea, abdominal pain
• Respiratory: Cough, dyspnea
• Dermatologic: Rash, pruritus

Serious Immune-Mediated Events:

• Pneumonitis, colitis, hepatitis, endocrinopathies (thyroiditis, adrenalitis, hypophysitis), nephritis
• Severe skin reactions including toxic epidermal necrolysis
• Encephalitis, myocarditis (rare but life-threatening)

Onset:
Can occur weeks to months after starting therapy; may also present after discontinuation

Management:
High-dose corticosteroids or permanent discontinuation depending on severity

• Corticosteroids or Immunosuppressants:
  May blunt immune response to nivolumab; avoid unless needed for toxicity management
• Live Vaccines:
  Avoid during treatment and for at least 5 months post-therapy
• CYP450 Interactions:
  None known, as nivolumab is not metabolized by liver enzymes
• Biologic Combinations:
  Use caution when combining with other immunomodulatory agents (e.g., other checkpoint inhibitors)

• FDA & EMA Updates (2024–2025):
• Expanded approvals for GI cancers and first-line NSCLC regimens
• Safety warnings updated to emphasize long-term immune-related risks
• NCCN Guidelines (2025):
• Nivolumab now a category 1 recommendation for multiple cancers including advanced melanoma, NSCLC, and RCC
• New Combinations Under Review:
• Dual checkpoint blockade (PD-1 + CTLA-4 inhibitors) for enhanced efficacy
• Addition to neoadjuvant protocols in early-stage cancers

• Vial Storage:
  Store refrigerated at 2°C to 8°C (36°F to 46°F)
  Protect from light; do not freeze or shake
• After Dilution:
  Stable up to 24 hours at 2°C to 8°C or 12 hours at room temperature (includes infusion time)
  Use within specified time; discard unused portion
• Handling Precautions:
  Use aseptic technique for preparation
  Use low-protein binding filters and infusion sets