The combination of nivolumab (PD-1 inhibitor) and ipilimumab (CTLA-4 inhibitor) is an FDA-approved dual checkpoint blockade regimen. It is approved across multiple tumor types and represents a cornerstone of modern immuno-oncology.
FDA-approved for: Unresectable or metastatic melanoma; Metastatic NSCLC (PD-L1 ≥1%); Advanced/metastatic RCC; Unresectable malignant pleural mesothelioma; dMMR/MSI-H metastatic CRC (2nd-line); Unresectable, locally advanced, or metastatic esophageal squamous cell carcinoma; Unresectable or metastatic HCC (with/without sorafenib).
Melanoma: Nivolumab 1 mg/kg IV + Ipilimumab 3 mg/kg IV every 3 weeks × 4 doses, then nivolumab 480 mg IV every 4 weeks.
NSCLC (PD-L1 ≥1%): Nivolumab 3 mg/kg IV + Ipilimumab 1 mg/kg IV every 6 weeks (with or without 2 cycles of chemotherapy).
RCC: Nivolumab 3 mg/kg IV + Ipilimumab 1 mg/kg IV every 3 weeks × 4 doses, then nivolumab 480 mg IV every 4 weeks.
Mesothelioma/MSI-H CRC/ESCC/HCC: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg IV every 6 weeks.
Fatigue (55%), Rash (40%), Diarrhea (45%), Nausea (28%), Pruritus (33%), Hypothyroidism (20%), Colitis (12%), Hepatitis (10%)
Adverse reaction frequencies reflect combination regimen data. Consult individual prescribing information for complete details.
Dual immune checkpoint blockade: Nivolumab blocks the PD-1 receptor on T cells, preventing PD-L1/PD-L2-mediated immune suppression in the tumor microenvironment. Ipilimumab blocks CTLA-4, a co-inhibitory receptor that suppresses T cell activation in lymph nodes. Together, they act at complementary stages of T cell activation — nivolumab at the effector phase and ipilimumab at the priming phase — resulting in synergistic anti-tumor immunity.