Opdivo (Nivolumab)
nivolumab — fully human IgG4 anti-PD-1 monoclonal antibody
Indications
Nivolumab carries one of the broadest FDA-approved indication portfolios of any immune checkpoint inhibitor. It is approved across more than a dozen solid tumour and haematological malignancy settings, as monotherapy or in combination with ipilimumab, chemotherapy, or cabozantinib. The following table summarises currently approved indications as of the March 2026 label revision.
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Unresectable / metastatic melanoma | Adults & paediatric ≥12 yr | Monotherapy or + ipilimumab | FDA Approved |
| Adjuvant melanoma (Stage IIB–IV resected) | Adults & paediatric ≥12 yr | Monotherapy | FDA Approved |
| Resectable NSCLC — neoadjuvant | Adults (≥4 cm or node+) | + platinum-doublet chemo | FDA Approved |
| Resectable NSCLC — neoadjuvant + adjuvant | Adults (no EGFR/ALK) | + platinum-doublet chemo → mono adjuvant | FDA Approved |
| Metastatic NSCLC — first-line (+ ipi) | Adults (PD-L1 ≥1%, no EGFR/ALK) | + ipilimumab | FDA Approved |
| Metastatic NSCLC — first-line (+ ipi + chemo) | Adults (no EGFR/ALK; any PD-L1) | + ipilimumab + 2 cycles platinum-doublet | FDA Approved |
| Metastatic NSCLC — second-line | Adults (post-platinum) | Monotherapy | FDA Approved |
| Malignant pleural mesothelioma | Adults (unresectable, first-line) | + ipilimumab | FDA Approved |
| Advanced RCC — first-line (+ ipilimumab) | Adults (intermediate/poor risk) | + ipilimumab | FDA Approved |
| Advanced RCC — first-line (+ cabozantinib) | Adults (all risk categories) | + cabozantinib | FDA Approved |
| Advanced RCC — second-line | Adults (prior anti-angiogenic) | Monotherapy | FDA Approved |
| Classical Hodgkin lymphoma — first-line (Stage III–IV) | Adults & paediatric ≥12 yr | + AVD (doxorubicin, vinblastine, dacarbazine) | FDA Approved |
| Classical Hodgkin lymphoma — relapsed/refractory | Adults (post-HSCT + BV, or ≥3 lines) | Monotherapy | FDA Approved |
| Recurrent / metastatic SCCHN | Adults (post-platinum) | Monotherapy | FDA Approved |
| Urothelial carcinoma — adjuvant | Adults (high recurrence risk) | Monotherapy | FDA Approved |
| Urothelial carcinoma — first-line metastatic | Adults | + cisplatin + gemcitabine | FDA Approved |
| Urothelial carcinoma — post-platinum | Adults (locally advanced or metastatic) | Monotherapy | FDA Approved |
| MSI-H/dMMR colorectal cancer | Adults & paediatric ≥12 yr | + ipilimumab (all lines) or monotherapy (post-chemo) | FDA Approved |
| Hepatocellular carcinoma | Adults (first-line or post-sorafenib) | + ipilimumab | FDA Approved |
| Esophageal / GEJ cancer — adjuvant | Adults (resected, residual disease post-CRT) | Monotherapy | FDA Approved |
| Esophageal squamous cell carcinoma | Adults (PD-L1 ≥1 for first-line) | + chemo or + ipilimumab; monotherapy 2L+ | FDA Approved |
| Gastric / GEJ / esophageal adenocarcinoma | Adults (PD-L1 ≥1) | + fluoropyrimidine-platinum chemo | FDA Approved |
Nivolumab was the second PD-1 inhibitor approved in the United States, receiving initial clearance for melanoma in December 2014. Its label has since been expanded to cover cancers across virtually every major organ system. The most recent label update (March 2026) includes biomarker-selected populations such as PD-L1-expressing NSCLC for first-line combination therapy and MSI-H/dMMR colorectal cancer. A subcutaneous formulation (Opdivo Qvantig, co-formulated with hyaluronidase) was approved in December 2024 for most adult solid tumour indications, though it is not indicated in combination with intravenous ipilimumab.
Small cell lung cancer (SCLC) — third-line+: Nivolumab monotherapy has been explored for metastatic SCLC after progression on platinum-based therapy and at least one other line. The initial accelerated approval was voluntarily withdrawn by BMS in 2021, though some institutions continue to offer it on a case-by-case basis. Evidence quality: moderate.
Non-clear-cell RCC: Some oncologists use nivolumab-based regimens in non-clear-cell subtypes based on extrapolation from pivotal RCC data. Evidence quality: low.
Dosing
Nivolumab dosing varies substantially by clinical scenario. No dose reductions are recommended; instead, treatment is withheld or permanently discontinued for immune-mediated toxicity. All IV doses are infused over 30 minutes. When given with ipilimumab, nivolumab is administered first on the same day.
Nivolumab Monotherapy
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Metastatic melanoma, NSCLC 2L, RCC 2L, SCCHN, UC 2L, ESCC 2L, cHL relapsed | 240 mg Q2W | 240 mg Q2W or 480 mg Q4W | 480 mg Q4W | Flat dosing for adults ≥40 kg. Continue until progression or unacceptable toxicity. Pediatric <40 kg: 3 mg/kg Q2W or 6 mg/kg Q4W |
| Adjuvant melanoma | 240 mg Q2W | 240 mg Q2W or 480 mg Q4W | 480 mg Q4W | Maximum treatment duration: 1 year or until recurrence Pediatric <40 kg: 3 mg/kg Q2W or 6 mg/kg Q4W |
| Adjuvant urothelial carcinoma | 240 mg Q2W | 240 mg Q2W or 480 mg Q4W | 480 mg Q4W | Maximum treatment duration: 1 year Start within 120 days of radical resection |
| Adjuvant esophageal / GEJ cancer | 240 mg Q2W | 240 mg Q2W or 480 mg Q4W | 480 mg Q4W | Total treatment duration: 1 year. Post-neoadjuvant CRT with residual pathologic disease. |
Nivolumab + Ipilimumab Combinations
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Melanoma — nivo 1 mg/kg + ipi 3 mg/kg | 1 mg/kg Q3W + ipi 3 mg/kg | 240 mg Q2W or 480 mg Q4W (mono) | 480 mg Q4W | Combination phase: max 4 doses, then nivolumab monotherapy Higher toxicity regimen; ipi at higher dose |
| HCC (first-line or post-sorafenib) — nivo 1 mg/kg + ipi 3 mg/kg | 1 mg/kg Q3W + ipi 3 mg/kg | 240 mg Q2W or 480 mg Q4W (mono) | 480 mg Q4W | Combination phase: max 4 doses, then single-agent nivolumab up to 2 years. |
| RCC first-line (intermediate/poor risk) — nivo 3 mg/kg + ipi 1 mg/kg | 3 mg/kg Q3W + ipi 1 mg/kg | 240 mg Q2W or 480 mg Q4W (mono) | 480 mg Q4W | Combination phase: 4 doses, then single-agent nivolumab. |
| Metastatic NSCLC first-line, mesothelioma — nivo 360 mg + ipi 1 mg/kg | 360 mg Q3W + ipi 1 mg/kg Q6W | Same (continuous) | 360 mg Q3W | Continue combination until progression, toxicity, or up to 2 years. For NSCLC, may add 2 cycles platinum-doublet chemo. |
| ESCC first-line (PD-L1 ≥1) — nivo + ipi | 3 mg/kg Q2W or 360 mg Q3W + ipi 1 mg/kg Q6W | Same (continuous) | 360 mg Q3W | Two nivolumab dosing options available. Continue until progression, toxicity, or up to 2 years. |
| MSI-H/dMMR CRC — nivo 240 mg + ipi 1 mg/kg | 240 mg Q3W + ipi 1 mg/kg | 240 mg Q2W or 480 mg Q4W (mono) | 480 mg Q4W | Combination phase: max 4 doses. Then monotherapy up to 2 years. Pediatric <40 kg: 3 mg/kg + ipi 1 mg/kg Q3W |
Nivolumab + Chemotherapy Combinations
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| NSCLC neoadjuvant (resectable) | 360 mg Q3W + platinum-doublet | N/A (3 cycles only) | 360 mg Q3W | 3 preoperative cycles. Neoadjuvant-only pathway. |
| NSCLC neoadjuvant + adjuvant | 360 mg Q3W + platinum-doublet | 480 mg Q4W (adjuvant, post-surgery) | 480 mg Q4W | Up to 4 neoadjuvant cycles, then up to 13 adjuvant cycles (~1 year). No EGFR/ALK. |
| Urothelial carcinoma first-line | 360 mg Q3W + cisplatin + gemcitabine | 240 mg Q2W or 480 mg Q4W (mono) | 480 mg Q4W | Combination phase: up to 6 cycles, then single-agent nivolumab up to 2 years. |
| Gastric / GEJ / esophageal adenocarcinoma (PD-L1 ≥1) | 360 mg Q3W or 240 mg Q2W + FP-platinum chemo | Same regimen (continuous) | 360 mg Q3W | Continue until progression, toxicity, or up to 2 years. Match nivolumab schedule to chemotherapy cycle. |
| ESCC first-line (PD-L1 ≥1) + chemotherapy | 240 mg Q2W or 480 mg Q4W + FP-platinum chemo | Same regimen (continuous) | 480 mg Q4W | Nivolumab continues up to 2 years; chemotherapy until progression or toxicity. |
| Classical Hodgkin lymphoma first-line (+ AVD) | 240 mg Q2W + AVD | N/A (6 cycles) | 240 mg Q2W | 6 treatment cycles total. G-CSF recommended from cycle 1. Pediatric <40 kg: 3 mg/kg Q2W |
Nivolumab + Cabozantinib
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Advanced RCC first-line | 240 mg Q2W or 480 mg Q4W + cabo 40 mg PO daily | Same (continuous) | 480 mg Q4W | Nivolumab up to 2 years; cabozantinib continues until progression. Take cabozantinib without food. |
Unlike cytotoxic chemotherapy, nivolumab is never dose-reduced. For Grade 3 immune-mediated adverse reactions, the drug is withheld and high-dose corticosteroids initiated. For Grade 4 or recurrent Grade 3 events, nivolumab is permanently discontinued. When given with ipilimumab, both agents are withheld or discontinued together. After completing the ipilimumab combination phase, the patient transitions to single-agent nivolumab maintenance.
Pharmacology
Mechanism of Action
Nivolumab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody that selectively binds the programmed death-1 (PD-1) receptor on activated T cells. Under normal physiological conditions, PD-1 engagement by its ligands PD-L1 and PD-L2 attenuates T-cell activity, serving as an immune checkpoint that prevents autoimmunity. Tumour cells exploit this pathway by overexpressing PD-L1 on their surface, effectively shielding themselves from cytotoxic T-cell recognition and destruction.
By binding PD-1 with high affinity (Kd ≈ 2.6 nmol/L), nivolumab prevents the PD-1/PD-L1 and PD-1/PD-L2 interactions, releasing the T-cell inhibitory brake. This restores anti-tumour immune surveillance and facilitates tumour-specific cytotoxic T-cell responses. When combined with ipilimumab (anti-CTLA-4), the dual checkpoint blockade produces complementary and non-redundant enhancement of T-cell activation.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | IV route (100% bioavailability); Tmax 1–4 h post-infusion end. SC formulation achieves comparable Cavg and Cmin at steady state. | SC administration provides equivalent exposure with no IV access requirement. PK is linear across the therapeutic dose range. |
| Distribution | Vdss = 6.8 L; limited extravascular distribution typical of large IgG molecules. | Small Vd reflects confinement primarily to vascular and interstitial spaces. Body weight modestly influences Vd but not in a clinically meaningful way. |
| Metabolism | Catabolised by non-specific proteolytic pathways; not CYP-mediated. FcRn recycling extends circulating half-life. | No hepatic CYP interactions. No dose adjustment required for mild hepatic impairment. FcRn-mediated recycling prevents lysosomal degradation. |
| Elimination | Terminal t½ = 25–27 days; CLss = 8.2 mL/h (geometric mean). Clearance decreases ~25% over time (time-varying CL). | Long half-life supports Q2W or Q4W flat dosing. Steady state reached by ~12 weeks with Q2W dosing. Time-varying CL may reflect tumour burden reduction. |
Side Effects
Nivolumab’s toxicity profile is dominated by immune-mediated adverse reactions (irAEs), which can affect virtually any organ system. The incidence and severity of adverse reactions are substantially higher when nivolumab is combined with ipilimumab compared to monotherapy. Data below are derived from pooled monotherapy analyses and landmark trials (CheckMate-066, -067, -577) as referenced in the FDA prescribing information.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Fatigue / asthenia | 49–59% | Most frequently reported; can be debilitating. Exclude thyroid dysfunction and adrenal insufficiency before attributing to drug effect. |
| Musculoskeletal pain | 32–42% | Includes arthralgia, myalgia, back pain. Usually manageable with analgesics; distinguish from immune-mediated arthritis. |
| Rash (all types) | 21–40% | Typically maculopapular; usually Grade 1–2. Vitiligo may occur in melanoma patients and is associated with treatment response. |
| Diarrhea | 18–36% | Most cases are low-grade; distinguish from immune-mediated colitis which may require corticosteroids and treatment interruption. |
| Nausea | 23–30% | Generally mild; rarely requires antiemetic escalation beyond standard measures. |
| Pruritus | 13–27% | Can be severe; topical emollients and antihistamines for Grade 1–2. Gabapentin may be useful for refractory pruritus. |
| Cough | 20–28% | Distinguish from immune-mediated pneumonitis; imaging warranted if persistent or worsening. |
| Decreased appetite | 22–29% | Monitor weight; consider endocrine causes such as adrenal insufficiency or hypothyroidism. |
| Constipation | 15–22% | Usually mild and manageable with standard bowel regimens. |
| Dyspnea | 14–24% | Requires prompt evaluation to exclude pneumonitis or disease progression. |
| Pyrexia | 14–22% | Low-grade fever is common; high fever warrants infection workup and consideration of immune-mediated aetiology. |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Hypothyroidism | 8–11% | Immune-mediated; permanent in most cases. Monitor TSH regularly; initiate levothyroxine replacement. |
| Hyperthyroidism | 3–7% | Often transient thyroiditis preceding hypothyroidism. Beta-blockers for symptomatic management. |
| Elevated AST / ALT | 3–8% | Screen for immune-mediated hepatitis. Withhold for >3× ULN; permanently discontinue for >8× ULN (monotherapy). |
| Pneumonitis (all grades) | 3–5% | Higher incidence in NSCLC. Grade ≥2 requires treatment interruption and systemic corticosteroids. |
| Infusion-related reactions | 1–4% | Grade 1–2 manageable with rate reduction; Grade 3–4 requires permanent discontinuation. |
| Colitis | 1–3% | Significantly higher with ipilimumab combinations (up to 13%). Requires prompt corticosteroid treatment. |
| Vitiligo | 3–9% | Primarily in melanoma populations; associated with improved tumour response and survival. |
| Peripheral neuropathy | 2–5% | Higher with chemotherapy combinations. Usually sensory and Grade 1–2. |
| Elevated creatinine | 2–4% | May indicate immune-mediated nephritis; withhold treatment and evaluate with renal biopsy if indicated. |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Immune-mediated pneumonitis | 3–5% (mono); up to 10% (+ ipi) | 2–24 months | Withhold for Grade 2; permanently discontinue for Grade 3–4. High-dose corticosteroids (1–2 mg/kg/day prednisone). |
| Immune-mediated colitis | 1–3% (mono); 10–13% (+ ipi) | 1–10 months | Withhold for Grade 2–3; permanently discontinue for Grade 4. Corticosteroids; infliximab for steroid-refractory cases. |
| Immune-mediated hepatitis | 1–3% (mono); 7–11% (+ ipi) | 1–6 months | Withhold for AST/ALT >3–8× ULN; permanently discontinue for >8× ULN. High-dose corticosteroids; add mycophenolate if refractory. |
| Immune-mediated myocarditis | <1% (rare but up to 45% fatality) | First 1–2 cycles | Permanently discontinue for Grade 2–4. High-dose corticosteroids. Consider additional immunosuppression. Cardiology consultation. |
| Immune-mediated nephritis | 1–2% | 2–12 months | Withhold for Grade 2–3 creatinine elevation; permanently discontinue for Grade 4. Corticosteroids; consider renal biopsy. |
| Immune-mediated endocrinopathies (adrenal insufficiency, hypophysitis, type 1 diabetes) | Adrenal: 1%; Hypophysitis: <1%; T1DM: <1% | Variable; weeks to months | Withhold for Grade 3–4 until clinically stable with hormone replacement. Lifelong replacement often required. |
| Severe dermatologic reactions (SJS, TEN, DRESS) | Rare (<1%) | Days to weeks | Withhold for suspected SJS/TEN/DRESS; permanently discontinue if confirmed. Dermatology and burns unit consultation. |
| Neurological toxicity (encephalitis, Guillain-Barré, myasthenia gravis) | Rare (<1%) | Variable | Withhold for Grade 2; permanently discontinue for Grade 3–4. High-dose corticosteroids; IVIG or plasmapheresis as indicated. |
| Reason for Discontinuation | Monotherapy | + Ipilimumab |
|---|---|---|
| Immune-mediated hepatitis | 1–2% | 8–11% |
| Immune-mediated colitis | <1% | 6–10% |
| Immune-mediated pneumonitis | 1–2% | 2–4% |
| Immune-mediated endocrinopathy | <1% | 2–3% |
| Rash / dermatologic | <1% | 2–3% |
The cornerstone of irAE management is early recognition and prompt corticosteroid initiation. For most Grade 2 immune-mediated reactions, withhold nivolumab and begin prednisone 0.5–1 mg/kg/day. For Grade 3–4 reactions, use methylprednisolone 1–2 mg/kg/day IV. Steroid-refractory colitis may respond to infliximab (5 mg/kg), while hepatitis may require mycophenolate. Once the event resolves to Grade 0–1 and the steroid taper is complete, rechallenge with nivolumab can be considered for monotherapy-related events, but rechallenge with combination ipilimumab is generally not recommended.
Drug Interactions
As a monoclonal antibody, nivolumab is eliminated through proteolytic catabolism and does not undergo cytochrome P450 metabolism. Formal drug-drug interaction studies have not been conducted. The primary interaction concerns involve pharmacodynamic effects on the immune system rather than pharmacokinetic changes.
Monitoring
-
Liver Function (AST, ALT, bilirubin)
Baseline, then before each cycle
Routine Threshold for withholding differs between monotherapy, ipilimumab combinations, and cabozantinib combinations. Monitor more frequently if elevations are detected. -
Renal Function (creatinine, eGFR)
Baseline, then before each cycle
Routine Rising creatinine may indicate immune-mediated nephritis. Withhold for Grade 2–3 elevation; permanently discontinue for Grade 4. -
Thyroid Function (TSH, free T4)
Baseline, then every 4–6 weeks
Routine Hypothyroidism develops in 8–11% of patients on monotherapy and is usually permanent. Hyperthyroidism may precede hypothyroidism (thyroiditis phase). -
Blood Glucose / HbA1c
Baseline, then periodically
Trigger-based Immune-mediated type 1 diabetes is rare but can present acutely with diabetic ketoacidosis. High index of suspicion for new-onset hyperglycaemia. -
Adrenal Function (AM cortisol, ACTH)
If symptoms suggest
Trigger-based Evaluate if fatigue, hypotension, or hyponatraemia develop. Adrenal insufficiency and hypophysitis may require lifelong hormone replacement. -
Pulmonary Symptoms / Chest Imaging
Baseline CT; re-image if respiratory symptoms develop
Trigger-based New or worsening cough, dyspnoea, or hypoxia should prompt urgent CT chest to evaluate for pneumonitis. Higher suspicion in NSCLC patients. -
Cardiac Biomarkers (troponin, BNP/NT-proBNP)
If cardiac symptoms develop
Trigger-based Check promptly for chest pain, dyspnoea, new arrhythmia, or heart failure symptoms. Myocarditis has high mortality if not recognised early. Consider baseline troponin before combination therapy. -
Complete Blood Count
Baseline, then before each cycle
Routine Especially important when co-administered with chemotherapy. Immune-mediated haemolytic anaemia and thrombocytopenia are rare but reported.
Contraindications & Cautions
Absolute Contraindications
The FDA prescribing information lists no absolute contraindications to nivolumab. However, clinical judgement dictates avoidance in the following situations:
- Life-threatening hypersensitivity to nivolumab or any excipient in a prior exposure.
- Combination with thalidomide analogues + dexamethasone for multiple myeloma — the FDA label explicitly warns of increased mortality with this combination outside of controlled clinical trials.
Relative Contraindications (Specialist Input Recommended)
- Active, severe autoimmune disease requiring systemic immunosuppression (e.g., lupus nephritis, active inflammatory bowel disease, organ transplant recipients). Risk of life-threatening flare or graft rejection.
- Prior organ transplantation: checkpoint inhibitor use may trigger acute allograft rejection. Decision requires multidisciplinary discussion with transplant specialists.
- Prior life-threatening irAE from any PD-1/PD-L1 or CTLA-4 inhibitor (e.g., Grade 4 myocarditis, fulminant hepatitis). Rechallenge carries substantial risk.
- Pregnancy or planned pregnancy: nivolumab can cause fetal harm based on its mechanism and animal data. Effective contraception required during treatment and for 5 months after last dose.
Use with Caution
- Controlled autoimmune conditions (e.g., well-managed rheumatoid arthritis, psoriasis): may be treated with close monitoring, but risk of flare is elevated.
- ECOG performance status ≥2: limited trial data; higher risk of treatment-related complications with diminished reserve.
- Pre-existing interstitial lung disease: higher baseline risk for treatment-emergent pneumonitis.
- Moderate-to-severe hepatic impairment: not formally studied; use with heightened monitoring.
- Elderly patients (≥75 years): similar efficacy but potentially higher irAE rates in some combination regimens.
In randomised clinical trials, adding a PD-1 blocking antibody (including nivolumab) to a thalidomide analogue plus dexamethasone for multiple myeloma resulted in increased mortality. Treatment of multiple myeloma patients with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials (FDA PI Section 5.5).
Nivolumab can cause severe and fatal immune-mediated adverse reactions in any organ system. The most clinically significant include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic reactions. These may occur during treatment or after discontinuation. Early identification with appropriate laboratory monitoring and prompt management with corticosteroids are essential. Complications of allogeneic haematopoietic stem cell transplantation can occur in patients who receive checkpoint inhibitors before or after transplant.
Patient Counselling
Purpose of Therapy
Nivolumab helps the patient’s own immune system recognise and attack cancer cells. It works differently from traditional chemotherapy — rather than killing dividing cells directly, it removes a “brake” that the tumour uses to hide from immune detection. Treatment is given by intravenous infusion (or subcutaneous injection for eligible patients) on a regular schedule and continues as long as there is clinical benefit without unacceptable side effects.
How to Take
Patients attend the infusion centre on their scheduled day. The IV infusion takes approximately 30 minutes. When given with ipilimumab, nivolumab is infused first, followed by ipilimumab, with separate infusion bags and lines. The subcutaneous formulation (Opdivo Qvantig) can be administered as an injection in approximately 5 minutes at the clinical site.
Sources
- Bristol-Myers Squibb. OPDIVO (nivolumab) injection, for intravenous use. Full Prescribing Information. Revised 03/2026. https://packageinserts.bms.com/pi/pi_opdivo.pdf Primary source for all dosing, indications, adverse reactions, and warnings in this monograph.
- U.S. FDA. FDA approves nivolumab and hyaluronidase-nvhy for subcutaneous injection. December 27, 2024. FDA.gov Regulatory basis for the subcutaneous Opdivo Qvantig approval across adult solid tumour indications.
- U.S. FDA. FDA approves nivolumab with ipilimumab for unresectable or metastatic MSI-H or dMMR colorectal cancer. April 8, 2025. FDA.gov Most recent indication expansion, converting MSI-H CRC from accelerated to regular approval.
- Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–330. doi:10.1056/NEJMoa1412082 CheckMate-066: established nivolumab superiority over dacarbazine in treatment-naive BRAF wild-type melanoma.
- Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381(16):1535–1546. doi:10.1056/NEJMoa1910836 CheckMate-067 five-year update: demonstrated 52% five-year OS with nivolumab + ipilimumab in advanced melanoma.
- Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Final, 10-year outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma: CheckMate 067. N Engl J Med. 2025;392(1):11–22. doi:10.1056/NEJMoa2407417 Landmark 10-year follow-up showing 43% OS rate with combination therapy, establishing long-term durability.
- Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384(13):1191–1203. doi:10.1056/NEJMoa2032125 CheckMate-577: basis for adjuvant nivolumab in resected esophageal/GEJ cancer with residual disease post-CRT.
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–1290. doi:10.1056/NEJMoa1712126 CheckMate-214: established nivolumab + ipilimumab as first-line standard for intermediate/poor-risk advanced RCC.
- NCCN Clinical Practice Guidelines in Oncology. Melanoma: Cutaneous. Version 2.2025. NCCN.org Incorporates nivolumab-based regimens as preferred options across melanoma treatment settings.
- Brahmer JR, Abu-Sbeih H, Ascierto PA, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2021;9(6):e002435. doi:10.1136/jitc-2021-002435 Comprehensive irAE management guidelines applicable to nivolumab mono- and combination therapy.
- Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol. 2018;18(3):153–167. doi:10.1038/nri.2017.108 Authoritative review of PD-1 biology underpinning nivolumab’s mechanism of action.
- Bajaj G, Wang X, Agrawal S, Gupta M, Roy A, Feng Y. Model-based population pharmacokinetic analysis of nivolumab in patients with solid tumors. CPT Pharmacometrics Syst Pharmacol. 2017;6(1):58–66. doi:10.1002/psp4.12143 Definitive population PK analysis from 11 trials establishing the two-compartment model and covariate effects on nivolumab clearance.
- Centanni M, Moes DJAR, Troconiz IF, Ciccolini J, van Hasselt JGC. Clinical pharmacokinetics and pharmacodynamics of immune checkpoint inhibitors. Clin Pharmacokinet. 2019;58(7):835–857. doi:10.1007/s40262-019-00748-2 Comprehensive PK/PD overview of checkpoint inhibitors including nivolumab, covering exposure-response relationships.