Ipilimumab

Evidence Level: L5

Predicted Indications: 1

Ipilimumab

Pharmacist Assessment Report

Ipilimumab: Choroideremia

One-Sentence Summary

Ipilimumab is a CTLA-4 checkpoint-blocking antibody, originally used to treat metastatic melanoma.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	Choroideremia
TxGNN Prediction Score	0.9906
Evidence Level	L5 as assigned by the automated scoring; a manual reading suggests L2 (see below)
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Proceed with Guardrails

Note on the top-ranked prediction: The highest-scoring prediction is choroideremia (0.9906). It has no supporting trials or literature, and no plausible link to CTLA-4 blockade. It is a monogenic retinal degeneration, and immune activation could be harmful. The score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, ipilimumab blocks CTLA-4, a negative regulator of T-cell activation. Blocking it enhances T-cell priming and anti-tumour immunity, which underlies its efficacy in cutaneous metastatic melanoma.

Non-cutaneous melanomas (mucosal, uveal and conjunctival) share a melanocytic origin with cutaneous melanoma, so CTLA-4 blockade is mechanistically plausible. These subtypes generally have a lower tumour mutational burden and typically lower response rates, so benefit may be more modest.

The Phase 3 trial labelled in the data (NCT02278887) does not test ipilimumab as the investigational agent. It compares tumour-infiltrating lymphocyte (TIL) cell therapy against ipilimumab. The L1 rating is therefore generous and should be confirmed manually. Direct support comes mainly from a completed Phase 2 trial of nivolumab plus ipilimumab in uveal melanoma (NCT02626962) and retrospective ipilimumab series, including an Australian one.

Clinical Trial Evidence

The 22 trials returned for this indication are mostly early-phase or combination studies. The most relevant are listed below.

Trial Number	Phase	Status	Enrolment	Key Findings
NCT02626962	Phase 2	Completed	52	Single-arm nivolumab plus ipilimumab in previously untreated metastatic uveal melanoma; most directly relevant trial
NCT02278887	Phase 3	Completed	168	TIL cell therapy with lymphodepletion and IL-2 versus ipilimumab in stage IV melanoma; ipilimumab is the comparator
NCT02506153	Phase 3	Active, not recruiting	1301	Pembrolizumab versus high-dose interferon or ipilimumab in high-risk resected melanoma
NCT05598853	Phase 1	Active, not recruiting	26	Intrathecal plus systemic anti-PD1/anti-CTLA-4 in leptomeningeal metastases from NSCLC or melanoma
NCT02983045	Phase 1/2	Completed	557	NKTR-214 with nivolumab, including a triplet with ipilimumab, in solid tumours
NCT03241173	Phase 1/2	Completed	52	INCAGN01949 combined with immune therapies in advanced malignancies
NCT03235245	Phase 2	Active, not recruiting	271	Encorafenib/binimetinib followed by ipilimumab/nivolumab versus immunotherapy alone in BRAF V600 melanoma
NCT04250246	Phase 2	Unknown	184	Nivolumab plus ipilimumab with or without guadecitabine in anti-PD-1-resistant melanoma and NSCLC
NCT04940299	Phase 2	Active, not recruiting	35	Tocilizumab with ipilimumab and nivolumab in advanced melanoma, NSCLC or urothelial carcinoma
NCT01769222	Phase 1	Terminated	3	Intratumoral ipilimumab with local radiation; terminated, little data

Several other listed trials (for example NCT06047379 and NCT04136470) are only loosely related to ipilimumab. No ANZCTR identifiers were available in the data compiled for this report.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
37887546	2023	Cohort	Curr Oncol	Real-world comparison of anti-PD-1 alone versus with ipilimumab in younger versus older adults with advanced melanoma
24999899	2014	Cohort	Med J Aust	Australian experience of ipilimumab in pretreated cutaneous, uveal and mucosal melanoma; efficacy and immune-related adverse events
28183255	2018	Review	Curr Cancer Drug Targets	Systematic review of adjuvant treatment of melanoma, noting that non-cutaneous melanoma is only about 5% of cases
29466692	2018	Review	Discov Med	Update on anti-PD-1 antibodies, alone or with ipilimumab, as frontline therapy in advanced melanoma
42178946	2026	Cohort	Pigment Cell Melanoma Res	Poliosis as a side effect of immunotherapy in cutaneous and non-cutaneous melanoma
40236344	2025	Case report	Cureus	Rare melanoma metastasis to the transverse colon; notes the risk of gastrointestinal perforation with immunotherapy

For related subtypes, the mucosal melanoma literature includes a dedicated ipilimumab 3 mg/kg expanded access analysis (24100024) and a pooled nivolumab with or without ipilimumab analysis (28056206).

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 15230N	Yervoy	Injection concentrate for I.V. infusion, 200 mg in 40 mL	Not available in the data compiled for this report

Cytotoxicity

Item	Content
Cytotoxicity Classification	Immunotherapy (anti-CTLA-4 monoclonal antibody), not a conventional cytotoxic
Myelosuppression Risk	Not a typical feature; please refer to the Product Information (PI) warnings and precautions
Emetogenicity Classification	Please refer to the PI warnings and precautions
Monitoring Items	Immune-related adverse events: liver function, thyroid function, and bowel, skin and endocrine symptoms. Confirm against the PI
Handling Protection	Please refer to the PI and local institutional policy

Safety Considerations

Label warnings and contraindications were not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for these.

Drug Interactions: 100 interactions were identified. Examples include:
- Major: anticoagulants (apixaban, edoxaban, betrixaban, dalteparin, argatroban, bivalirudin, desirudin, danaparoid)
- Moderate: corticosteroids (hydrocortisone, prednisone, prednisolone, dexamethasone, betamethasone, budesonide, triamcinolone), metronidazole, tinidazole, naltrexone, rosuvastatin, simvastatin
- Corticosteroids are also used to manage immune-related adverse events, so their use should be planned deliberately.
Safety signals in the retrieved literature: Case reports describe fatal myocarditis with rhabdomyolysis, encephalitis, colitis and pneumonitis with ipilimumab-containing regimens.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Ipilimumab is already marketed in Australia for melanoma. CTLA-4 blockade is mechanistically plausible in non-cutaneous melanoma, and there is a completed Phase 2 trial in uveal melanoma plus retrospective mucosal melanoma data. However, the automated L1 rating is not well supported, because the Phase 3 trial does not test ipilimumab directly. A manual rating of about L2 is more defensible. Response rates are expected to be lower than in cutaneous melanoma.

To proceed, the following is needed:

Manual confirmation of the evidence level, and review of the published results of NCT02626962
ARTG approved indication text and TGA Product Information, including warnings and contraindications
Mechanism of action data from DrugBank
A safety monitoring plan for immune-related adverse events, including cardiac, neurological and gastrointestinal events
A review of interactions with anticoagulants and corticosteroids
Subtype-specific efficacy data for mucosal, uveal and conjunctival melanoma, ideally including Australian data
Disclaimer

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