177Lu-P17-088 PSMA-targeted radioligand therapy for metastatic castration-resistant prostate cancer

Prospective Clinical Trial of Low-dose 177Lu-P17-088 in the Treatment of Metastatic Castration-Resistant Prostate Cancer

This study will try low-dose 177Lu-P17-088, a PSMA-targeted radioligand, to treat people with PSMA-positive metastatic castration-resistant prostate cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 90 Years
• Sex: Male
• Sponsor: First Affiliated Hospital of Fujian Medical University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Fuzhou, Fujian)
• Trial ID: NCT07562438 on ClinicalTrials.gov

What this trial studies

This single-arm Phase 2 trial gives fixed-activity 177Lu-P17-088 (3.7 GBq ±10%) every 6–8 weeks for up to four cycles to patients with PSMA-positive mCRPC. P17-088 includes an albumin-binding moiety designed to prolong circulation and increase tumor uptake relative to non-albuminized PSMA ligands. Preliminary first-in-human data showed higher tumor accumulation with detectable bone marrow and kidney distribution and clinical responses at low activity doses. Safety and efficacy are monitored during treatment and with a 30-day short-term follow-up after treatment discontinuation.

Who should consider this trial

Good fit: Ideal candidates are adults with PSMA-positive metastatic castration-resistant prostate cancer who have progressive disease on castrate-level testosterone and have had one to two prior taxane regimens (or who are ineligible/refuse them) with adequate organ function.

Not a fit: Patients who lack PSMA expression on imaging, have poor bone marrow or renal function, or require immediate alternative systemic therapy are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, this agent could deliver higher tumor radiation with a favorable safety profile, potentially improving tumor control while allowing lower or less frequent dosing.

How similar studies have performed: Other PSMA-targeted radioligand therapies such as 177Lu-PSMA-617 have shown clinical benefit in mCRPC, but the albumin-binding P17-088 modification is newer and has limited clinical data to date.

Eligibility criteria

Inclusion Criteria:

1. Metastatic Castration-Resistant Prostate Cancer (mCRPC) mCRPC refers to prostate cancer that progresses despite serum testosterone at castrate levels (\< 50 ng/dL or 1.7 nmol/L), meeting at least one of the following criteria:

   * PSA \>1 ng/mL with two consecutive rises at least 1 week apart, each increase ≥ 50% above the nadir.
   * Radiographic progression: Either two or more new bone lesions on bone scan, or soft tissue lesion progression as per RECIST 1.1 criteria. Progression based on symptoms alone is insufficient for mCRPC diagnosis and requires further evaluation.
2. Failure of, Refusal of, Absence of, or Refractoriness to Standard Therapy, or Disease Progression, or No Available Standard Therapy per Current Guidelines:

   * Patients who have not received, refused, or progressed after receiving at least 1 but no more than 2 prior taxane-based therapies. The taxane regimen must have included exposure for at least 2 cycles. Patients who received only one taxane may be included if the investigator deems them unsuitable for a second taxane (e.g., due to frailty assessed by geriatric/comorbidity evaluation or intolerance).
   * Patients who have progressed after receiving at least one novel androgen axis drug \[NAAD\] (e.g., abiraterone, enzalutamide).
3. Ability to understand and voluntarily sign a written informed consent form (ICF), and willingness and ability to comply with trial procedures including examinations and follow-up.
4. Age 18-90 years (inclusive).
5. Expected survival \> 6 months.
6. ECOG performance status ≤ 2.
7. Presence of high-uptake lesions confirmed by 68Ga-PSMA-11 PET/CT imaging (positive defined as lesion uptake \>1.5 times the liver background).
8. At least one measurable lesion per RECIST 1.1 criteria OR at least one bone metastasis per PCWG3 criteria.
9. Adequate organ function (No blood products, growth factors, or albumin administered within 14 days prior to baseline lab tests):

   * Bone Marrow Function: Neutrophil count ≥ 1.5 × 10#/L, White blood cell count ≥ 3.0 × 10\^9/L, Platelet count ≥ 100 × 10\^9/L, Hemoglobin ≥ 10 g/dL (≥ 100 g/L).
   * Liver Function: Albumin ≥ 30 g/L, Total bilirubin ≤ 1.5 × ULN, ALT or AST ≤ 3.0 × ULN (without liver metastases) or ≤ 5.0 × ULN (with liver metastases).
   * Renal Function: Serum creatinine ≤ 1.5 × ULN.
10. Agreement to comply with prescribed radiation protection measures during the trial period.

Exclusion Criteria:

1. Inability to tolerate imaging procedures;
2. Patients who have received systemic anticancer therapy (e.g., chemotherapy, radiotherapy, immunotherapy; excluding endocrine therapy), investigational drugs, or device therapy within 4 weeks prior to dosing;
3. Patients who received radionuclide therapy (Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, Lutetium-177) within 6 months, or any External Beam Radiation Therapy (EBRT) within 2 months prior to the first dose;
4. Patients with unresolved Grade 4 myelosuppression from prior anticancer therapy within 2 weeks, or Grade 3 myelosuppression requiring \>6 weeks for recovery;
5. Planned use of cytotoxic chemotherapy, antitumor immunotherapy, radioligand therapy, or similar agents during the study;
6. Use of blood products or albumin within 14 days before dosing to meet enrollment criteria;
7. Brain metastasis at screening, except:

   * Asymptomatic cases confined to supratentorial/cerebellar regions (no midbrain/pons/medulla/spinal cord involvement) without corticosteroid therapy and with lesions ≤1.5 cm;
   * Symptomatic cases with treated and radiologically stable lesions (\>4 weeks);
8. Other malignancies within 5 years (excluding cured localized cancers like basal/squamous cell skin carcinoma);
9. Superscan on bone scintigraphy;
10. Symptomatic or impending spinal cord compression;
11. Prior EBRT involving extensive bone marrow (\>25%);
12. Significant cardiac disease at screening, including:

    * QTcF \>470 ms or long QT syndrome history;
    * Myocardial infarction, angina, or CABG within 6 months deemed ineligible by investigators;
13. Any condition that, per investigator judgment, may compromise safety, data interpretation, or indicate high risk;
14. Uncontrolled bladder outlet obstruction, urinary incontinence, claustrophobia, or radiophobia at screening;
15. Positive for HCV-Ab, HIV, or syphilis antibodies at screening;
16. HBsAg-positive patients with active HBV replication (confirmed by HBVDNA per investigator assessment);
17. Known allergy to proteins/peptides, excipients, or structurally related compounds;
18. History of drug/alcohol abuse within 1 year or chronic substance abuse;
19. Failure to use effective contraception during the trial and for 6 months post-last dose;
20. Severe active infection prior to the first administration.

Where this trial is running

Fuzhou, Fujian

• Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University — Fuzhou, Fujian, China (Recruiting)

Study contacts

• Study coordinator: Weibing Miao, MD

Conditions Prostate Cancer