PM02734

Summary

Elisidepsin (PM02734, Irvalec) is an investigational marine‑derived cyclic depsipeptide that disrupts cancer cell plasma membranes. It has been evaluated intravenously in early‑phase trials for a range of advanced solid tumours, including lung, colorectal, mesothelioma and gastro‑oesophageal cancers. The drug remains experimental and has not received regulatory approval for any indication.

Mechanism of Action

Elisidepsin is described as a plasma‑membrane‑disrupting agent. By inserting into the lipid bilayer of tumour cells, it compromises membrane integrity, leading to rapid cell lysis and death. This non‑receptor‑mediated cytotoxicity differs from many conventional chemotherapies that target DNA replication or specific signalling pathways.

What the Research Shows

Phase I studies identified reversible hepatic transaminase elevation as the dose‑limiting toxicity and established flat‑dose regimens ranging from 2 mg to 11 mg for further testing. One trial reported a complete response lasting over three years in an esophageal cancer patient and several cases of disease stabilisation lasting three months or longer across tumour types. However, a phase Ib/II gastro‑oesophageal cancer trial found no objective responses and halted enrolment due to lack of efficacy. A combination study with erlotinib was closed because frequent dose delays and limited activity made the regimen unattractive. Overall, early clinical data suggest modest activity in a subset of patients but no consistent tumour shrinkage.

Reported Benefits

Evidence from early trials shows that elisidepsin can achieve prolonged disease stabilisation in some heavily pre‑treated patients and, in a single case, a durable complete response. The drug’s membrane‑targeting mechanism appears to avoid myelotoxicity and may be combined with other agents, although the erlotinib combination proved problematic.

Limitations of the Evidence

No objective tumour regressions have been confirmed in larger cohorts, and the phase Ib/II study in gastro‑oesophageal cancer was stopped for lack of efficacy. Sample sizes are small, and the drug’s activity appears limited to disease stabilisation rather than tumour shrinkage. The need for intravenous infusion and hepatic toxicity further constrain its development.

Safety Considerations

The most common adverse events are reversible grade 3/4 elevations in hepatic transaminases and occasional bilirubin rise, which define the maximum‑tolerated dose. Other frequent, mostly mild to moderate, effects include pruritus, nausea, fatigue, hypersensitivity reactions, rash, and diarrhoea (when combined with erlotinib). No myelotoxicity or cumulative toxicity has been reported, and hepatic changes resolve after dose interruption.

How It Is Administered

Elisidepsin is administered exclusively by intravenous infusion. Clinical studies have used 30‑minute, 3‑hour, 24‑hour, or fortnightly infusion schedules, typically every three weeks or weekly, with flat‑dose amounts (e.g., 2 mg to 11 mg) rather than body‑surface‑area dosing.

Routes of Administration

Goals & Uses

• RNA splicing inhibitionMolecular TargetModerate
• Antitumor activity in solid tumorsOncologyModerate
• Targeting EGFR/ErbB3-expressing tumorsOncologyModerate

Contraindications

• Severe hepatic impairmentOrganHighLiver function concerns
• Known hypersensitivity to elisidepsin or excipientsAllergy/hypersensitivityHigh

Adverse Effects

• Peripheral neuropathyNeurologicalUncommon
• HepatotoxicityHepaticUncommonLiver injury or dysfunction
• Nausea and vomitingGastrointestinalCommon
• FatigueGeneralCommonLow energy or tiredness
• MyelosuppressionHematologicUncommon

Drug Interactions

• CYP3A4 inhibitorsModerate
• Other spliceosome inhibitorsHigh

Population Constraints

• PregnancyReproductive SafetyAbsolute
• Pediatric patientsAgeRelative
• Patients with severe renal impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionInvestigationalDeveloped by PharmaMar (Spain); no EMA marketing authorization granted.
• United StatesInvestigationalStudied in Phase I/II trials; no FDA approval obtained.
• United KingdomUnknownNo known separate MHRA approval; followed EU investigational status.

PM02734 has been studied in Phase I and Phase II clinical trials for solid tumors, including non-small cell lung cancer and head and neck cancers, but has not received regulatory approval in any major jurisdiction.

Evidence & Sources

• Phase I, dose-escalating study of elisidepsin (Irvalec(®)), a plasma membrane-disrupting marine antitumor agent, in combination with erlotinib in patients with advanced malignant solid tumors
  Journal ArticleModerateGoel S, et al.2016-01-01T00:00:00.000000Z
• First-in-human, phase I study of elisidepsin (PM02734) administered as a 30-min or as a 3-hour intravenous infusion every three weeks in patients with advanced solid tumors
  Journal ArticleModerateRatain MJ, et al.2015-01-01T00:00:00.000000Z
• A phase I and pharmacokinetic study of elisidepsin (PM02734) in patients with advanced solid tumors
  Journal ArticleModerateSalazar R, et al.2012-01-01T00:00:00.000000Z
• Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial)
  Journal ArticleModeratePetty R, et al.2016-01-01T00:00:00.000000Z
• Cancer treatments: can we find treasures at the bottom of the sea?
  Journal ArticleModerateProvencio M, et al.2009-01-01T00:00:00.000000Z
• Marine Peptides as Anticancer Agents: A Remedy to Mankind by Nature
  Journal ArticleModerateNegi B, Kumar D, Rawat DS2017-01-01T00:00:00.000000Z

Frequently Asked Questions