Phase 2 Clinical Trial of 177Lu-P17-088 for mAPMR Prostate Cancer

Prior treatment

• 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;
• 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;
• Patients with unresolved Grade 4 myelosuppression from prior anticancer therapy within 2 weeks, or Grade 3 myelosuppression requiring \>6 weeks for recovery;
• Planned use of cytotoxic chemotherapy, antitumor immunotherapy, radioligand therapy, or similar agents during the study;
• 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);
• Prior EBRT involving extensive bone marrow (\>25%);
• Severe active infection prior to the first administration.

Other illness

• Other malignancies within 5 years (excluding cured localized cancers like basal/squamous cell skin carcinoma);
• Any condition that, per investigator judgment, may compromise safety, data interpretation, or indicate high risk;
• Positive for HCV-Ab, HIV, or syphilis antibodies at screening;
• HBsAg-positive patients with active HBV replication (confirmed by HBVDNA per investigator assessment);
• Known allergy to proteins/peptides, excipients, or structurally related compounds;
• History of drug/alcohol abuse within 1 year or chronic substance abuse;
• Failure to use effective contraception during the trial and for 6 months post-last dose;

Lab values

• Use of blood products or albumin within 14 days before dosing to meet enrollment criteria;
• 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;

Other

• Inability to tolerate imaging procedures;
• Superscan on bone scintigraphy;
• Symptomatic or impending spinal cord compression;
• Uncontrolled bladder outlet obstruction, urinary incontinence, claustrophobia, or radiophobia at screening;

• metastatic androgen pathway modulation resistant (mAPMR) prostate cancer refers to Prostate cancer with distant metastases and sustained castrate testosterone (\< 50 ng/dL or 1.7 nmol/L) during APM therapy, meeting ≥1 criterion:
  • PSA nadir ≥1.0 ng/mL, absolute PSA rise ≥0.2 ng/mL confirmed ≥21 days apart;
  • Radiographic progression: RECIST 1.1 soft tissue progression, or bone scan progression per PCWG4 2+2 rule (≥6 new bone lesions confirmed on single scan); PSMA-PET new metastatic lesions also qualify as progression.
• 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).
• 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.
• Age 18-90 years (inclusive).
• Expected survival \> 6 months.
• ECOG performance status ≤ 2.
• Presence of high-uptake lesions confirmed by 68Ga-PSMA-11 PET/CT imaging (positive defined as lesion uptake \>1.5 times the liver background).
• At least one measurable soft tissue lesion per RECIST version 1.1 criteria, OR at least one bone metastasis on bone scintigraphy, OR at least one PSMA-positive metastatic lesion on PSMA-PET/CT, all as defined by PCWG4.
• 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\^9/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.
• Agreement to comply with prescribed radiation protection measures during the trial period.