Ipilimumab

證據等級: L5

預測適應症: 2 個

Ipilimumab: From Cutaneous Melanoma to Non-Cutaneous Melanoma

One-Sentence Summary

Ipilimumab is an anti-CTLA-4 monoclonal antibody whose established use is in cutaneous melanoma, where checkpoint blockade is now standard of care. The TxGNN model predicts it may also be effective in non-cutaneous melanoma (uveal/mucosal subtypes), a direction already supported by 50 clinical trials and 5 publications identified in this evidence pack.

Quick Overview

Item	Content
Original Indication	Melanoma (cutaneous) — established anti-CTLA-4 checkpoint indication; formal New Zealand license text is not available (drug not currently marketed in NZ)
Predicted New Indication	Non-cutaneous melanoma (uveal/mucosal)
TxGNN Prediction Score	99.02%
Evidence Level	L1
New Zealand Market Status	Not marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed DrugBank mechanism-of-action text was not available in this evidence pack. Based on known pharmacology, ipilimumab is an anti-CTLA-4 monoclonal antibody that blocks an inhibitory co-stimulatory checkpoint on T cells, releasing the brake on anti-tumour T-cell activation. This mechanism already underlies its established role in cutaneous melanoma, either as monotherapy or combined with nivolumab (anti-PD-1).

Non-cutaneous melanoma subtypes (uveal and mucosal) arise from the same melanocyte lineage and are known to exploit CTLA-4-dependent immune evasion, giving biological plausibility to extending checkpoint blockade beyond the cutaneous subtype. However, uveal and mucosal melanomas have a lower tumour mutational burden and a distinct immune microenvironment compared with cutaneous disease, and historically show lower response rates to checkpoint inhibitors. This means the mechanistic rationale is sound, but efficacy cannot simply be assumed to transfer 1:1 from cutaneous melanoma — subgroup-specific evidence (see below) is what actually supports this candidate.

Note: A second candidate flagged by TxGNN, choroideremia (score 99.06%, rank 7176), was excluded from this report. It is a CHM-gene retinal degeneration with no known biological connection to CTLA-4 signalling, has zero supporting trials or literature, and was scored L5/Hold — most likely a knowledge-graph embedding artifact rather than a genuine repurposing signal.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02224781	Phase 3	Active, not recruiting	267	DREAMseq: compares sequencing of ipilimumab+nivolumab vs. dabrafenib+trametinib in unresectable/metastatic BRAF-mutant melanoma — highest-grade direct evidence for treatment sequencing
NCT01654692	Phase 2	Completed	86	Ipilimumab + fotemustine in unresectable locally advanced or metastatic melanoma; safety and efficacy assessed
NCT01927419	Phase 2	Completed	142	Randomized, double-blind: nivolumab + ipilimumab vs. ipilimumab monotherapy in previously untreated unresectable/metastatic melanoma
NCT02939300	Phase 2	Completed	18	Ipilimumab + nivolumab in melanoma leptomeningeal metastases — direct evidence in a difficult-to-treat subgroup
NCT04133948	Phase 1/2	Completed	44	DONIMI trial: neoadjuvant domatinostat + nivolumab ± ipilimumab in IFN-γ-signature-low stage III melanoma
NCT01496807	Phase 1	Completed	31	Ipilimumab (Yervoy) + peginterferon (Sylatron) tolerability and autoimmune antibody effects in advanced melanoma

Literature Evidence

PMID	Year	Type	Journal	Key Findings
28183255	2018	Review	Current Cancer Drug Targets	Systematic review of melanoma adjuvant trials (2000–2015); positions checkpoint inhibitors within evolving adjuvant landscape
29466692	2018	Review	Discovery Medicine	Clinical update on anti-PD-1 antibodies alone or combined with ipilimumab as frontline therapy for advanced melanoma
24999899	2014	Cohort/Expanded Access	Medical Journal of Australia	Real-world efficacy/tolerability of ipilimumab in pretreated cutaneous, uveal, and mucosal melanoma — directly evaluates the non-cutaneous subgroup
37887546	2023	Cohort	Current Oncology	Retrospective cohort comparing survival outcomes with anti-PD-1 ± ipilimumab by age group in advanced melanoma
40236344	2025	Case Report	Cureus	Case of metastatic melanoma to the transverse colon treated with immunotherapy; highlights GI perforation as an immune-related adverse event

New Zealand Market Information

Ipilimumab is not currently marketed in New Zealand — no authorizations are on record.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Immunotherapy (anti-CTLA-4 immune checkpoint inhibitor)
Myelosuppression Risk	Low — direct myelosuppression is uncommon; risk profile is dominated by immune-related adverse events rather than bone marrow suppression
Emetogenicity Classification	Low
Monitoring Items	Please refer to the package insert warnings and precautions
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The mechanistic rationale is sound and is backed by L1-level evidence, including a completed randomized Phase 2 trial and real-world cohort data specifically covering uveal and mucosal melanoma, plus a large body of supportive Phase 3 trials in the broader melanoma population. However, non-cutaneous subtypes are known to respond less robustly to checkpoint blockade than cutaneous melanoma, so guardrails around subtype-specific efficacy expectations are warranted.

To proceed, the following is needed:

Detailed mechanism-of-action documentation (DrugBank MOA field is currently a data gap)
TFDA/NZ package insert warnings and contraindications (currently a blocking data gap — DG001)
Subgroup-specific efficacy data isolating uveal vs. mucosal melanoma response rates
New Zealand regulatory pathway assessment, given the drug is not currently marketed there
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.