Preclinical Validation of [¹⁷⁷Lu]Lu-AKIR001, a CD44v6-Targeted Radiotherapeutic Entering First-in-Human Trials

Area of Science:

• Oncology
• Nuclear Medicine
• Radiopharmaceutical Therapy

Background:

• Targeted radionuclide therapy is a promising cancer treatment.
• The CD44v6 antigen is a potential pan-cancer target.
• ¹⁷⁷Lu-labeled AKIR001 targets CD44v6 for therapy.

Purpose of the Study:

• Evaluate the therapeutic efficacy, biodistribution, dosimetry, and safety of ¹⁷⁷Lu-labeled AKIR001.
• Assess its potential as a pan-cancer therapy targeting CD44v6.

Main Methods:

• Preclinical biodistribution and dosimetry in CD44v6-expressing xenografts.
• Therapeutic efficacy studies in 3 xenograft models with varying dosing and combinations.
• Toxicology in rabbits and PET imaging in cynomolgus macaques.

Main Results:

• [¹⁷⁷Lu]Lu-AKIR001 showed high, selective tumor uptake and favorable dosimetry predictions.
• Significant dose-dependent efficacy was observed, with complete tumor regression in 80% of animals in a radioresistant model using fractionated dosing.
• Preclinical toxicology studies indicated a good safety profile with low uptake in normal tissues and no adverse effects.

Conclusions:

• Data strongly support the therapeutic efficacy, safety, and dosimetry of [¹⁷⁷Lu]Lu-AKIR001.
• The findings justify the advancement of [¹⁷⁷Lu]Lu-AKIR001 into clinical trials.
• A Phase 1 clinical trial is currently recruiting patients with CD44v6-positive solid cancers.