TheranosticTrials.org

Clinical Trial · NCT07363486

Sequential Study of 225Ac-LNC1011 in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Overview

PSMA is an ideal target for the precise diagnosis and treatment of prostate cancer. LNC1011 is a novel albumin-binding PSMA-targeted compound. This study aims to investigate the safety and efficacy of different doses of 225Ac-labeled LNC1011 in the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) and to explore the optimal therapeutic dose.

Sponsor

First Affiliated Hospital of Fujian Medical University

Phase

Phase 1/2

Contacts

Weibing Miao, MD (STUDY_CHAIR)

Guochang Wang, MD (CONTACT)

guochang1007@163.com

+86-0591-87981619

Weibing Miao, MD (CONTACT)

miaoweibing@126.com

+86-0591-87981618

ClinicalTrials.gov

NCT07363486

Drug / Compound

LNC1011

Isotope(s):
Target(s):
  • PSMA
Ligand Class: Small Molecules

Eligibility

Inclusion

  • Expected survival \> 6 months.
  • At least one measurable lesion per RECIST 1.1 criteria OR at least one bone metastasis per PCWG3 criteria.
  • Failure of, Refusal of, Absence of, or Refractoriness to Standard Therapy, or Disease Progression, or No Available Standard Therapy per Current Guidelines:
  • PSA \>1 ng/mL with two consecutive rises at least 1 week apart, each increase ≥50% above the nadir.
  • Coagulation: INR ≤ 1.5; Activated partial thromboplastin time (APTT) ≤ 2 × ULN (for patients not on anticoagulation or on stable-dose anticoagulation).
  • Bone Marrow Function: Neutrophil count ≥ 1.5 × 10#/L, White blood cell count ≥ 3.0 × 10#/L, Platelet count ≥ 100 × 10#/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).
  • 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:
  • ECOG performance status ≤ 2.
  • 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).
  • Presence of high-uptake lesions confirmed by 68Ga-PSMA-11 PET/CT imaging (positive defined as lesion uptake \>1.5 times the liver background).
  • 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.
  • Renal Function: Serum creatinine ≤ 1.5 × ULN.
  • Agreement to comply with prescribed radiation protection measures during the trial period.
  • Adequate organ function (No blood products, growth factors, or albumin administered within 14 days prior to baseline lab tests):
  • Patients who have progressed after receiving at least one novel androgen axis drug \[NAAD\] (e.g., abiraterone, enzalutamide).

Exclusion

  • Other malignancies within 5 years (excluding cured localized cancers like basal/squamous cell skin carcinoma);
  • QTcF \>470 ms or long QT syndrome history;
  • Brain metastasis at screening, except:
  • Failure to use effective contraception during the trial and for 6 months post-last dose;
  • 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;
  • Positive for HCV-Ab, HIV, or syphilis antibodies at screening;
  • Patients with unresolved Grade 4 myelosuppression from prior anticancer therapy within 2 weeks, or Grade 3 myelosuppression requiring \>6 weeks for recovery;
  • Uncontrolled bladder outlet obstruction, urinary incontinence, claustrophobia, or radiophobia at screening;
  • Any condition that, per investigator judgment, may compromise safety, data interpretation, or indicate high risk;
  • Planned use of cytotoxic chemotherapy, antitumor immunotherapy, radioligand therapy, or similar agents during the study;
  • Symptomatic or impending spinal cord compression;
  • Use of blood products or albumin within 14 days before dosing to meet enrollment criteria;
  • 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;
  • Significant cardiac disease at screening, including:
  • Prior EBRT involving extensive bone marrow (\>25%);
  • Superscan on bone scintigraphy;
  • Asymptomatic cases confined to supratentorial/cerebellar regions (no midbrain/pons/medulla/spinal cord involvement) without corticosteroid therapy and with lesions ≤1.5 cm;
  • Myocardial infarction, angina, or CABG within 6 months deemed ineligible by investigators;
  • Known allergy to proteins/peptides, excipients, or structurally related compounds;
  • Symptomatic cases with treated and radiologically stable lesions (\>4 weeks);
  • Severe active infection prior to the first administration.
  • Inability to tolerate imaging procedures;
  • HBsAg-positive patients with active HBV replication (confirmed by HBVDNA per investigator assessment);
  • History of drug/alcohol abuse within 1 year or chronic substance abuse;