A Phase 1 open-label, dose-finding multi-center trial of [ 177Lu]Ludotadipep in metastatic castration-resistant prostate cancer patients, followed by an open-label, repeat dose, multi-center Phase 2a trial to assess safety and efficacy
INTRODUCTION
Prostate cancer is the most common malignant tumor in men and is the second leading cause of cancer-related deaths in men, second only to lung cancer.
Endocrine therapy (including surgery, chemotherapy or anti-ADT or combined androgen blockade therapy) is a preferred treatment for prostate cancer. This treatment is very effective for the majority of subjects at the initial stage but after a median period of treatment for 14 to 30 months, almost all subjects will gradually develop mCRPC with a median survival of less than 20 months, and new treatments are required.
Since treatment guidelines for patients with mCRPC have yet to be established, chemotherapy is commonly used. While it extends the survival period by inhibiting the progress of the disease, it also comes with the general side effects of chemotherapy drugs.
PSA (Prostate-specific antigen) is a protein synthesized in the epithelial cells of the prostate and is rarely expressed in tissues other than the prostate, so it is a useful biomarker for prostate cancer screening. However, PSA is specific to prostate tissues but not for tumors. Thus, it may be overexpressed in benign diseases such as benign prostate hypertrophy, prostatitis, and prostate infarction.
PSMA (Prostate Specific Membrane Antigen) is a protein that increases as the disease progresses; thus, it is recognized as a biomarker for the diagnosis and treatment of prostate cancer.
The use of radioisotopes with short half-lives for PET scans makes images clearer because the isotope has been cleared from normal tissues leaving the isotope mostly in cancer tissues. However, therapeutic radiopharmaceuticals generally have longer half-lives; therefore, it is effective to allow as much uptake to the diseased tissue as possible. If the albumin protein abundant in blood is used as a drug carrier, the drug can be maintained in the blood for a prolonged length of time; thus, it can be taken up heavily by the diseased tissue to increase the therapeutic effect of the treatment.
A wide variety of PSMA-targeting radioligands have been developed in recent years and used in the treatment of a variety of cancers. Currently, [177Lu]Lu-PSMA-617 is the best-known and most frequently used PSMA radioligand for therapeutic application and treatment of prostate cancer in humans.
[177Lu]Lu-PSMA-617 is a potential alternative to cabazitaxel in men with mCRPC, with greater activity but less severe side-effects and improvements in patient-reported outcomes.
PSMA-targeting radioligands modified with albumin-binding entities have enhanced blood circulation in comparison to [177Lu]Lu-PSMA-617 and, as a consequence, considerably increased accumulation in the tumor tissue, which correlated with better therapeutic outcomes in preclinical settings
FutureChem Co., Ltd. has developed an albumin binder loaded [177Lu]Ludotadipep, which showed high therapeutic efficiency, with low non-target tissue uptake in preclinical studies. To date (09 Dec 2021), at doses up to 100 mCi, no patient has experienced any adverse effects immediately after injection, and no DLTs or relevant hepatotoxicity, nephrotoxicity or hepatotoxicity have been observed. The most common adverse effect post-injection is mild nausea that is readily controlled.
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