Evorpacept

Summary

Evorpacept (ALX148) is an investigational CD47-blocking fusion protein developed by ALX Oncology. By antagonizing the CD47–SIRPα 'don't eat me' checkpoint, it promotes phagocytic clearance of tumor cells. It is being evaluated in Phase 2/3 clinical trials in combination with standard oncology regimens for hematologic malignancies and solid tumors, including gastric/gastroesophageal junction cancer, head and neck squamous cell carcinoma, and myeloid malignancies.

Mechanism of Action

Evorpacept is a high-affinity SIRPα-Fc fusion protein that blocks the CD47 'don't eat me' signal on tumor cells, enabling macrophage-mediated phagocytosis of cancer cells. It selectively binds CD47 on tumor cells without significantly affecting normal red blood cells, thereby promoting anti-tumor innate immunity when combined with tumor-targeting antibodies or other agents.

Routes of Administration

Goals & Uses

• Breast cancer treatmentOncologyLow
• Gastric/Gastroesophageal Junction Cancer TreatmentOncologyModerate
• Acute Myeloid Leukemia (AML) TreatmentHematology/OncologyModerate
• Head and neck squamous cell carcinoma treatmentOncologyModerate
• Myelodysplastic Syndromes (MDS) TreatmentHematology/OncologyModerate

Contraindications

• Severe uncontrolled autoimmune diseaseAutoimmuneModerate
• Known severe hypersensitivity to evorpacept or its componentsAllergy/ImmunologyHigh

Adverse Effects

• ThrombocytopeniaHematologicUncommonLow platelet count
• AnemiaHematologicCommonLow red blood cell count or hemoglobin
• NeutropeniaHematologicUncommonLow neutrophil count
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• FatigueGeneralCommonLow energy or tiredness
• Infusion-related reactionsHypersensitivityCommon

Drug Interactions

• AzacitidineLow
• TrastuzumabLow
• PembrolizumabLow

Population Constraints

• Severe renal or hepatic impairmentOrgan FunctionRelative
• PregnancyReproductive SafetyRelative
• Pediatric patientsAgeRelative

Regulatory Status

• European UnionInvestigationalUnder clinical investigation; no EMA approval as of 2024.
• United StatesInvestigationalFDA Fast Track Designation granted for select indications. Multiple ongoing Phase 2/3 trials (e.g., MOUNTAINEER-03). IND active.
• United KingdomInvestigationalNo MHRA approval; part of international clinical trial programs.

Not yet approved by FDA, EMA, or other major regulatory agencies. Received Fast Track Designation from the FDA for certain oncology indications. Investigated under multiple INDs in the US and internationally.

Evidence & Sources

No sources recorded yet.