Nivolumab
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
- Nivolumab
- Nivolumab: From Non-Small Cell Lung Cancer and Metastatic Melanoma to Non-Cutaneous Melanoma
Nivolumab: From Non-Small Cell Lung Cancer and Metastatic Melanoma to Non-Cutaneous Melanoma
One-Sentence Summary
Nivolumab is a PD-1 immune checkpoint inhibitor originally used for non-small cell lung cancer, squamous cell lung carcinoma, and metastatic melanoma. The TxGNN model predicts it may be effective for non-cutaneous melanoma (for example mucosal, uveal and other non-skin subtypes). Currently, 40 clinical trials and 9 publications are linked to this prediction, but most trials are early-phase combination studies and the literature is mainly cohort studies and case reports.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Non-small cell lung carcinoma, lung cancer, squamous cell lung carcinoma, metastatic melanoma (the Singapore licence records contain no indication text) |
| Predicted New Indication | Non-cutaneous melanoma |
| TxGNN Prediction Score | 98.41% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From the pharmacology records, nivolumab is an antibody that targets programmed cell death 1 (PD-1, gene PDCD1). Blocking PD-1 is understood to restore T-cell antitumour activity. This is the same mechanism that underlies its approved use in melanoma.
Non-cutaneous melanomas (mucosal, uveal and other subtypes) are melanocyte-derived cancers that share PD-1/PD-L1 axis biology with cutaneous melanoma. They usually respond less well, often because of a lower mutational burden, so benefit should not be assumed to match that seen in skin melanoma.
Other melanoma subtypes also appear in the ranked predictions. Mucosal melanoma and acral lentiginous melanoma each reach L2 and the same "Proceed with Guardrails" decision. Several other subtypes have only case reports or no data.
Clinical Trial Evidence
The table lists the most relevant trials from the 40 linked to this prediction. All trials are single-arm or early-phase, or involve combinations. None is a completed Phase 3 efficacy trial for non-cutaneous melanoma.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07576725 | Phase 2 | Not yet recruiting | 50 | Low-dose, reduced-frequency nivolumab in unresectable or metastatic cancer, including non-cutaneous melanoma; no results yet |
| NCT00441337 | Phase 1 | Completed | 39 | First-in-human dose-escalation and safety study of MDX-1106 (nivolumab) in advanced solid tumours including melanoma |
| NCT02304458 | Phase 1/2 | Completed | 140 | Nivolumab alone or with ipilimumab in children and young adults with recurrent or refractory solid tumours; melanoma relevance is partial |
| NCT02626962 | Phase 2 | Completed | 52 | Nivolumab plus ipilimumab in previously untreated metastatic uveal melanoma (single-arm) |
| NCT05297565 | Phase 3 | Completed | 14 | Subcutaneous vs intravenous nivolumab (pharmacokinetic non-inferiority) in resected stage III/IV melanoma; small and not an efficacy trial |
| NCT03025256 | Phase 1 | Active, not recruiting | 75 | Intravenous plus intrathecal nivolumab for melanoma and lung cancer with leptomeningeal disease |
| NCT05598853 | Phase 1 | Active, not recruiting | 26 | Intrathecal plus systemic anti-PD-1/anti-CTLA-4 in melanoma or NSCLC with leptomeningeal metastasis |
| NCT02831933 | Phase 2 | Terminated | 11 | Radiotherapy plus gene therapy followed by nivolumab in NSCLC and metastatic uveal melanoma |
| NCT03903458 | Phase 1 | Unknown | 21 | Tinostamustine plus nivolumab in refractory or metastatic melanoma |
| NCT06265285 | Phase 2 | Recruiting | 50 | In-home vs in-clinic subcutaneous nivolumab; a care-delivery study, not efficacy |
Related trials for the mucosal and acral lentiginous subtypes include NCT05384496 (axitinib plus PD-1 blockade in mucosal melanoma, Phase 2, recruiting), NCT05089370 (decitabine/cedazuridine plus nivolumab in mucosal melanoma, Phase 1/2, 8 patients) and NCT02978443 (nivolumab plus ipilimumab in mucosal and acral melanoma, Phase 2, terminated at 14 patients).
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26841210 | 2016 | Cohort | J Eur Acad Dermatol Venereol | Single-institution study of cutaneous and non-cutaneous melanomas treated with nivolumab |
| 37887546 | 2023 | Cohort | Curr Oncol | Effectiveness of anti-PD-1 alone or with ipilimumab in younger vs older adults with advanced melanoma |
| 30510916 | 2018 | Cohort | Front Oncol | Serum soluble CD163 as a possible predictive marker of nivolumab effectiveness in advanced cutaneous melanoma |
| 34176837 | 2022 | Case report | Intern Med | Marked tumour shrinkage with nivolumab in mediastinal malignant melanoma |
| 28171845 | 2017 | Case report | Int J Surg Case Rep | Marked response to nivolumab in metastatic anorectal amelanotic melanoma |
| 42178946 | 2026 | Case series | Pigment Cell Melanoma Res | Poliosis developing in melanoma patients (cutaneous and non-cutaneous) on immunotherapy |
| 40236344 | 2025 | Case report | Cureus | Rare melanoma metastasis to the transverse colon; notes immunotherapy-related GI perforation risk |
| 41774417 | 2025 | Case report | Pigment Cell Melanoma Res | Epidermotropic metastatic melanoma that continued to form new lesions despite adjuvant nivolumab |
| 30549256 | 2019 | Cohort | Int J Rheum Dis | Good oncological response associated with rheumatic immune-related adverse events after PD-1 therapy |
Stronger evidence exists for specific non-cutaneous subtypes. Examples are a pooled analysis of nivolumab with or without ipilimumab in mucosal melanoma (28056206), a multicentre Phase 2 trial of nivolumab in mucosal melanoma (31938955) and an analysis of anti-PD-1 efficacy in acral and mucosal melanoma (27533633). One retrospective series suggests adjuvant nivolumab may not improve disease-free survival in acral lentiginous melanoma (36093750).
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14975P | OPDIVO Concentrate for Solution for Infusion 10 mg/ml | Infusion, solution concentrate | Not available in the licence record |
| SIN15117P | NIVOLUMAB BMS Concentrate for Solution for Infusion 10 mg/ml | Infusion, solution concentrate | Not available in the licence record |
| SIN16852P | OPDUALAG Concentrate for Solution for Infusion 240 mg/80 mg | Infusion, solution concentrate | Not available in the licence record |
All three licences are valid single-ingredient registrations, and the product is marketed in Singapore as an injectable only.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Immunotherapy (anti-PD-1 monoclonal antibody; not a conventional cytotoxic agent) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert; literature signals suggest monitoring for immune-related adverse events (for example colitis, myocarditis, skin and rheumatic reactions) |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions (14 records):
- Major: lenalidomide, pomalidomide and thalidomide.
- Moderate: corticosteroids (hydrocortisone, triamcinolone, dexamethasone, betamethasone, budesonide, prednisolone, prednisone, methylprednisolone, deflazacort) and idelalisib.
- The corticosteroid interactions matter because steroids are the usual treatment for immune-related adverse events.
- Signals from the literature (case reports, not label data): fatal myocarditis with rhabdomyolysis after ipilimumab plus nivolumab, late-onset fulminant myocarditis, sarcoid-like pulmonary granulomatosis, capillary leak syndrome, bullous pemphigoid and colitis.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Nivolumab is already marketed in Singapore, and the PD-1 mechanism is shared with its approved melanoma use. Phase 2 and observational evidence supports activity in non-cutaneous melanoma, particularly mucosal and acral subtypes. However, no completed Phase 3 trial for this indication exists, response rates are lower than in cutaneous melanoma, and the evidence comes largely from combination, early-phase or small terminated studies.
To proceed, the following is needed:
- Singapore package insert (warnings, contraindications and approved indications), which is not yet available in the compiled data
- Mechanism of action data from DrugBank
- Subtype-specific efficacy data (mucosal, uveal and acral), ideally from randomised or larger prospective studies, including Asian populations
- An immune-related adverse event monitoring plan, with attention to myocarditis and to steroid use
- Review of results from the ongoing Phase 2 trials in mucosal and acral melanoma
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.