Elisidepsin
Also known as: Elisidepsin, IB-01212, Irvalec, PM027, PM02734
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Summary
Elisidepsin (Irvalec®, PM02734) is an investigational synthetic cyclic depsipeptide derived from marine sources. It has been studied as a single agent and in combination with other chemotherapies for advanced solid tumours, including gastro‑oesophageal cancers. The drug is administered intravenously and is being evaluated for its ability to disrupt cancer cell membranes and induce tumour regression.
Mechanism of Action
Elisidepsin belongs to the kahalalide family of marine depsipeptides. Pre‑clinical data, as noted in early clinical reports, describe it as a plasma‑membrane‑disrupting agent that inserts into lipid bilayers, causing rapid loss of membrane integrity and triggering cell death pathways in tumour cells. The exact molecular targets remain under investigation, but membrane perturbation appears central to its anticancer activity.
What the Research Shows
Phase I dose‑escalation studies identified a maximum‑tolerated dose of 6.8 mg/m² and a recommended flat dose of 10 mg for single‑agent use, with reversible grade 3 transaminase elevations as the dose‑limiting toxicity. One patient with esophageal adenocarcinoma achieved a complete response lasting over 38 months, and disease stabilization was observed in 12 patients. Combination trials with erlotinib, carboplatin, or gemcitabine failed to demonstrate added efficacy and were limited by overlapping toxicities and dose delays. A phase Ib/II trial in metastatic gastro‑oesophageal cancer showed acceptable safety but no objective responses, leading to early termination of the study. Overall, early signals of activity have not been reproduced in larger or combination settings.
Reported Benefits
Limited clinical data suggest elisidepsin can produce durable responses in a minority of patients, as evidenced by a single complete response and multiple cases of disease stabilization in phase I trials. The drug’s membrane‑disrupting mechanism may offer a novel approach distinct from conventional cytotoxics, potentially benefiting tumours resistant to other agents.
Limitations of the Evidence
Evidence of efficacy is confined to small phase I cohorts; subsequent phase II and combination studies have not confirmed antitumour activity. The number of patients evaluated is low, and most trials report only stable disease or no response. Lack of pharmacokinetic interactions does not offset the frequent dose‑delays and limited therapeutic benefit, leaving the clinical value of elisidepsin uncertain.
Safety Considerations
The most common adverse events are reversible elevations in liver transaminases (ALT/AST) and bilirubin, which have been dose‑limiting at higher doses. Other reported toxicities include rash, pruritus, diarrhoea (when combined with erlotinib), fatigue, nausea, anorexia, thrombocytopenia, and mild‑moderate myalgia. Toxicities are generally manageable with dose adjustments and are not associated with cumulative organ damage.
How It Is Administered
Elisidepsin is given by intravenous infusion, either as a 24‑hour infusion every three weeks or as shorter (3‑hour) infusions on a weekly or bi‑weekly schedule. Clinical studies have used both flat‑dose (mg) and body‑surface‑area‑based dosing, with later trials favoring a flat‑dose approach for simplicity.
Routes of Administration
Goals & Uses
- Solid tumor oncologyOncologyModerate
- Treatment of non-small cell lung cancer (NSCLC)OncologyLow
- Anticancer activity in solid tumorsOncologyModerate
- Membrane-targeting cytotoxicityMechanistic/ResearchModerate
- Treatment of head and neck squamous cell carcinomaOncologyLow
Contraindications
- Severe hepatic impairmentOrganHighLiver function concerns
- Severe renal impairmentOrganModerateKidney function concerns
- Poor performance status (ECOG >2)Clinical StatusHigh
- Known hypersensitivity to the peptide or formulation excipientsAllergyHigh
Adverse Effects
- Peripheral neuropathyNeurologicalUncommon
- HypotensionCardiovascularUncommonLow blood pressure
- Infusion‑related reactions (e.g., flushing, dyspnea)Infusion ReactionCommon
- Nausea and vomitingGastrointestinalCommon
- NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
- FatigueGeneralCommonLow energy or tiredness
- MyelosuppressionHematologicUncommon
- Elevated liver enzymesHepaticUncommonIncrease in AST/ALT or other hepatic markers
- Mucositis/stomatitisGastrointestinalUncommon
Drug Interactions
- CYP3A4 inhibitorsModerate
- Other cytotoxic chemotherapeuticsModerate
- CYP450 inhibitors or inducersLow
Population Constraints
- PregnancyReproductive SafetyAbsolute
- Pediatric patientsAgeRelative
- Breastfeeding womenReproductiveAbsolute
- LactationReproductiveAbsolute
- Elderly patients (>75 years)AgeRelative
- Pregnant womenReproductiveAbsolute
Regulatory Status
- European UnionInvestigationalClinical trial authorisation; not approved by EMA.
- United StatesInvestigationalInvestigational New Drug (IND) status; no FDA approval.
- United KingdomInvestigationalUnder clinical investigation; not licensed by MHRA.
Phase II clinical trials completed for colorectal cancer and melanoma; not approved in any major jurisdiction.
Evidence & Sources
- Journal ArticleModerateGoel S, et al.2016-01-01T00:00:00.000000Z
- Journal ArticleModerateSalazar R, et al.2012-01-01T00:00:00.000000Z
- Journal ArticleModeratePetty R, et al.2016-01-01T00:00:00.000000Z
- Journal ArticleModerateGoldwasser F, et al.2014-01-01T00:00:00.000000Z
- Journal ArticleModerateNegi B, Kumar D, Rawat DS2017-01-01T00:00:00.000000Z
- Journal ArticleModerateWyer S, et al.2022-01-01T00:00:00.000000Z
Frequently Asked Questions
What type of cancer has elisidepsin been tested in?
Clinical trials have enrolled patients with advanced solid tumours, including esophageal, gastro‑oesophageal junction, gastric, and various other refractory malignancies. Most studies focused on heavily pre‑treated populations.
Is elisidepsin an approved cancer drug?
No. Elisidepsin remains investigational and has not received regulatory approval for any indication. It is being evaluated in early‑phase clinical trials.
What are the main side effects to watch for?
The principal safety concerns are reversible liver enzyme elevations (ALT, AST, bilirubin) and, in combination regimens, skin rash, diarrhoea, and fatigue. Most adverse events are mild to moderate and resolve after dose modification.
How is the drug given to patients?
Elisidepsin is administered intravenously, either as a prolonged 24‑hour infusion every three weeks or as shorter infusions given weekly or every two weeks, depending on the study protocol.
Has elisidepsin shown clear benefit in trials?
Early phase I data reported one complete response and several cases of disease stabilization, but later phase II and combination studies failed to demonstrate objective tumour responses, leading to discontinuation of further development in those settings.
What is Elisidepsin?
Elisidepsin (Irvalec®, PM02734) is an investigational synthetic cyclic depsipeptide derived from marine sources. It has been studied as a single agent and in combination with other chemotherapies for advanced solid tumours, including gastro‑oesophageal cancers. The drug is administered intravenously and is being evaluated for its ability to disrupt cancer cell membranes and induce tumour regression.
What is Elisidepsin used for?
Elisidepsin is educationally associated with: Solid tumor oncology, Treatment of non-small cell lung cancer (NSCLC), Anticancer activity in solid tumors, Membrane-targeting cytotoxicity, Treatment of head and neck squamous cell carcinoma. Educational only — not medical advice.
How is Elisidepsin administered?
Recorded routes of administration: Intravenous.
What are the potential side effects of Elisidepsin?
Reported adverse effects include: Peripheral neuropathy, Hypotension, Infusion‑related reactions (e.g., flushing, dyspnea), Nausea and vomiting, Nausea, Fatigue, Myelosuppression, Elevated liver enzymes, Mucositis/stomatitis. This list is not exhaustive — consult a qualified clinician.
Who should avoid Elisidepsin?
Recorded contraindications: Severe hepatic impairment, Severe renal impairment, Poor performance status (ECOG >2), Known hypersensitivity to the peptide or formulation excipients. Consult a qualified clinician before use.