177Lu-LNC1011 in Patients with Metastatic Castration-resistant Prostate Cancer

Phase 1

Recruiting

• Conditions: Metastatic Castration-resistant Prostate Cancer
• Interventions: Drug: 177Lu-LNC1011

• Registration Number: NCT06250244
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

This study employed an open-label, non-randomized design, representing the first human trial of its kind. It utilized a standard 3+3 dose-escalation approach, focusing on patients with metastatic castration-resistant prostate cancer, initiating treatment at a dose of 1.85 GBq over a 6-week period. Subsequent cohorts underwent sequential 50% dose escalations until the observation of dose-limiting toxicity (DLT).

Detailed Description

\[177Lu\]Lu-LNC1011 is a novel long-circulating PSMA therapeutic probe. This study represents the first human investigation, aiming to explore its maximum tolerated dose (MTD), safety, dosimetry, and initial treatment efficacy in patients with metastatic castration-resistant prostate cancer (mCRPC).This study employed an open-label, non-randomized design, representing the first human trial of its kind. It utilized a standard 3+3 dose-escalation approach, focusing on patients with metastatic castration-resistant prostate cancer, initiating treatment at a dose of 1.85 GBq over a 6-week period. Subsequent cohorts received a dose escalation of 0.925 GBq from the previous cohort.

Study Timeline

• Study Start: 2023-05-01
• Study First Submitted: 2024-01-10
• Status Verified: 2024-02
• Study First Submitted QC: 2024-02-07
• Study First Posted: 2024-02-09
• Last Update Submitted: 2024-12-06
• Last Update Posted: 2024-12-11
• Primary Completion: 2025-04-01
• Study Completion: 2025-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 12

Inclusion Criteria

• progressive metastatic castration-resistant prostate cancer
• tumors with high PSMA expression confirmed on 68Ga-PSMA PET/CT PSMA expression confirmed on 68Ga-PSMA PET/CT

Exclusion Criteria

• a serum creatinine level of more than 150 μmol per liter
• a hemoglobin level of less than 10.0 g/dl
• a white-cell count of less than 4.0× 109/L
• a platelet count of less than 100 × 109/L
• a total bilirubin level of more than 3 times the upper limit of the normal range
• a serum albumin level of more than 3.0 g per deciliter
• cardiac insufficiency

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LNC1011 Dose escalation	177Lu-LNC1011	Patients received a single dose of 1.85 GBq (50 mCi) of 177Lu-LNC1011 via intravenous injection, followed by monitoring at 3, 24, 48, 72, and 168 hours post-injection. Subsequent cohorts received a dose escalation of 0.925 GBq from the previous cohort.

Primary Outcome Measures

Name	Time	Method
Hematologic adverse events collection	through study completion, an average of 6 months	Hematologic status were performed before and every 2 weeks after administration of radiopharmaceutical. Adverse events were categorized using the Common Toxicity Criteria for Adverse Events 5.0:Total white cell count less than 2.5 × 10\^9/L,Platelet count less than 75 × 10\^9/L
Dosimetry of normal organs and tumors	through study completion, an average of 4 weeks	The semiquantitative dosimetry will be performed based on SPECT/CT acquisitions after the first administration of 177Lu-LNC1011. The dose delivered to normal organs and tumors will be recorded.
Liver and renal toxic events collection	through study completion, an average of 6 months	Liver and renal function were performed before and 4 weeks after administration of radiopharmaceutical. Adverse events were categorized using the Common Toxicity Criteria for Adverse Events 5.0:Progressive deterioration of organ function (GFR \<30 mL/min or creatinine \> 2-fold upper limit of normal (ULN); liver enzymes \> 5-fold ULN).

Secondary Outcome Measures

Name	Time	Method
PSA Response	through study completion, an average of 6 months	The serum PSA response was documented semimonthly until 6 weeks after the administration of 177Lu-LNC1011. PSA response was classified as the following: partial response (PR) if PSA decrease ≥50%, progressive disease (PD) if PSA increase ≥ 25% and stable disease (SD) if PSA increase \<25% or PSA decrease \<50%.
Pharmacokinetics and dosimetry	Whole-body (WB) scans were performed at 2, 4, 24, 48, 72, 120, and 168 hours following intravenous administration of [177Lu]Lu-LNC1011	Absorbed doses were measured in the brain, salivary glands, thyroid, cardiac content, lungs, liver, kidneys, spleen, pancreas, L2-L4 lumbar vertebrae, gastric content, and bladder content.

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China