Pegilodecakin

Summary

Pegilodecakin (AM0010) is a PEGylated recombinant human IL-10 being investigated as an immunotherapy for solid tumors, particularly in combination with checkpoint inhibitors and chemotherapy. It stimulates cytotoxic CD8+ T cells while suppressing pro-inflammatory myeloid cell activity. Clinical trials in pancreatic cancer, renal cell carcinoma, and non-small cell lung cancer have been conducted, with mixed efficacy results.

Mechanism of Action

Pegilodecakin is a PEGylated form of recombinant human interleukin-10 (rHuIL-10) that binds to the IL-10 receptor, activating JAK1/TYK2 signaling and STAT3 phosphorylation. It exerts pleiotropic immunomodulatory effects including suppression of pro-inflammatory cytokines (TNF-α, IL-1, IL-6, IL-12) and stimulation of CD8+ T cell and NK cell anti-tumor activity, promoting immune surveillance against cancer.

Routes of Administration

Goals & Uses

• Immune checkpoint combination therapyImmunotherapyModerate
• Pancreatic cancer treatmentOncologyModerate
• Non-small cell lung cancer treatmentOncologyLow
• 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

Adverse Effects

• Injection site reactionsLocalCommon
• ThrombocytopeniaHematologicCommonLow platelet count
• HypertriglyceridemiaMetabolicUncommon
• AnemiaHematologicCommonLow red blood cell count or hemoglobin
• FatigueGeneralCommonLow energy or tiredness
• Elevated inflammatory markers / flu-like symptomsConstitutionalCommon

Drug Interactions

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

Population Constraints

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

Regulatory Status

• European UnionInvestigationalNot approved by EMA; investigated in clinical trials only.
• United StatesInvestigationalFDA Fast Track designation granted for pancreatic adenocarcinoma. Not approved. SEQUOIA Phase III trial failed primary endpoint. Development status uncertain following Eli Lilly acquisition of ARMO BioSciences.
• United KingdomInvestigationalNot approved by MHRA; clinical trial participation only.

Has received FDA Fast Track designation for certain oncology indications. Not approved by FDA, EMA, or other major regulatory agencies. Development has faced setbacks due to insufficient efficacy in pivotal trials (e.g., SEQUOIA trial in pancreatic cancer). Developed by ARMO BioSciences, later acquired by Eli Lilly.

Evidence & Sources

No sources recorded yet.