Pegilodecakin

Summary

Pegilodecakin is an investigational pegylated form of interleukin‑10 (IL‑10) administered by subcutaneous injection. Developed as an immunoregulatory cytokine, it is being evaluated in early‑phase clinical trials for solid tumours, most notably advanced renal cell carcinoma, where it is used alone or together with checkpoint inhibitors, tyrosine‑kinase inhibitors, or chemotherapy.

Mechanism of Action

Pegilodecakin is a pegylated recombinant human IL‑10 that retains IL‑10’s ability to modulate immune responses. While IL‑10 suppresses chronic inflammation, it also promotes the expansion and activation of antigen‑specific CD8+ T cells, driving production of IFNγ, granzymes and up‑regulation of MHC class I and II on tumour cells. Pegylation extends systemic exposure, allowing sustained signalling through the IL‑10 receptor on tumour‑infiltrating lymphocytes and enhancing antitumour immunity.

What the Research Shows

Early‑phase studies (phase 1/1b) across multiple solid tumours reported immunologic activity and objective responses with pegilodecakin monotherapy in renal cell carcinoma and uveal melanoma. Combination trials showed higher response rates when pegilodecakin was added to anti‑PD‑1 antibodies, tyrosine‑kinase inhibitors (e.g., pazopanib) or chemotherapy (FOLFOX). In the IVY phase 1/1b study of heavily pretreated renal cell carcinoma, pegilodecakin plus anti‑PD‑1 yielded a 43% objective response rate, median progression‑free survival of 13.9 months and promising 1‑year overall‑survival probabilities. A systematic review of checkpoint‑inhibitor regimens in clear‑cell RCC listed pegilodecakin as a component of effective combos. However, later phase II/III trials have not demonstrated clear superiority over standard therapies in renal, non‑small‑cell lung or pancreatic cancers, and efficacy signals remain mixed.

Reported Benefits

Clinical data suggest pegilodecakin can boost tumour‑specific CD8+ T‑cell activity, increase IFNγ levels, and improve response rates when combined with PD‑1 blockade or targeted agents, particularly in renal cell carcinoma. Early trials reported objective response rates up to 43% and median progression‑free survival exceeding one year in heavily pretreated patients, indicating potential for durable disease control in a subset of patients.

Limitations of the Evidence

Evidence is largely confined to early‑phase, non‑randomised studies with limited patient numbers. Phase II/III results have not confirmed superior efficacy over existing standards in renal, lung or pancreatic cancers. The benefit appears tumour‑type specific and may not extend beyond renal cell carcinoma. Long‑term outcomes and comparative effectiveness remain unestablished.

Safety Considerations

Pegilodecakin has a manageable safety profile in early trials. The most frequently reported grade 3/4 adverse events include anemia, thrombocytopenia and hypertriglyceridaemia. Overall, safety was consistent across monotherapy and combination arms, and no unexpected toxicities were observed when added to checkpoint inhibitors or tyrosine‑kinase inhibitors.

How It Is Administered

Pegilodecakin is administered by subcutaneous injection, leveraging pegylation to achieve an extended half‑life that supports less frequent dosing schedules. It is investigated both as a single agent and in combination with anti‑PD‑1 antibodies, tyrosine‑kinase inhibitors, or chemotherapy regimens.

Routes of Administration

Goals & Uses

• Immune checkpoint combination therapyImmunotherapyModerate
• Pancreatic cancer treatmentOncologyModerate
• Non-small cell lung cancer treatmentOncologyLow
• reduce tumor‑associated inflammationOncologyLow
• Enhance anti‑tumor immunityOncologyModerate
• Renal cell carcinoma treatmentOncologyModerate
• Anti-tumor immunity enhancementOncologyModerate

Contraindications

• Severe hepatic impairmentOrganModerateLiver function concerns
• Active infectionInfectiousModerate
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Active autoimmune diseaseAutoimmunityHigh
• hypersensitivity to IL‑10 or PEGImmunologicModerate

Adverse Effects

• Injection site reactionsLocalCommon
• ThrombocytopeniaHematologicUncommonLow platelet count
• HypertriglyceridemiaMetabolicUncommon
• AnemiaHematologicUncommonLow red blood cell count or hemoglobin
• FatigueGeneralCommonLow energy or tiredness
• Elevated inflammatory markers / flu-like symptomsConstitutionalCommon
• Injection‑site reactionLocalCommon

Drug Interactions

• Immunosuppressants (e.g., corticosteroids)Moderate
• FOLFOX chemotherapyModerate
• PembrolizumabLow

Population Constraints

• PregnancyReproductive SafetyAbsolute
• Severe renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative
• Pregnant or lactating womenReproductiveRelative
• Patients with prior severe immune-related adverse eventsImmunologicRelative

Regulatory Status

• European UnionInvestigationalUnder clinical investigation; EMA has not granted marketing authorisation.
• United StatesInvestigationalPhase II/III trials ongoing; not FDA‑approved.
• United KingdomInvestigationalNot approved by MHRA; clinical trial participation only.

Not approved by FDA or EMA; currently enrolled in Phase II/III clinical trials for melanoma, renal cell carcinoma and other solid tumours.

Evidence & Sources

• Efficacy and Safety of Checkpoint Inhibitors in Clear Cell Renal Cell Carcinoma: A Systematic Review of Clinical Trials
  Journal ArticleHighFarrukh M, et al.2023-01-01T00:00:00.000000Z
• Pegylated Interleukin-10: Clinical Development of an Immunoregulatory Cytokine for Use in Cancer Therapeutics
  Journal ArticleModerateAutio K, Oft M2019-01-01T00:00:00.000000Z
• Immune regulation and cytotoxic T cell activation of IL-10 agonists - Preclinical and clinical experience
  Journal ArticleModerateOft M2019-01-01T00:00:00.000000Z
• Pegilodecakin as monotherapy or in combination with anti-PD-1 or tyrosine kinase inhibitor in heavily pretreated patients with advanced renal cell carcinoma: Final results of cohorts A, G, H and I of IVY Phase I study
  Journal ArticleModerateTannir NM, et al.2021-01-01T00:00:00.000000Z
• PEGylated IL-10: Clinical Development in Cancer Immunotherapy, Where to Go?
  Journal ArticleModerateCavallazzi Sebold B, et al.2023-01-01T00:00:00.000000Z
• Interleukin-10 in cancer immunotherapy: from bench to bedside
  Journal ArticleModerateSalkeni MA, Naing A2023-01-01T00:00:00.000000Z

Frequently Asked Questions