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

A Dosimetry Study and Dose-escalation and of [177Lu]Lu-LNC1011 in Metastatic Castration-Resistant Prostate Cancer Patients

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).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: 177Lu-LNC1011

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 Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhaohui Zhu, MD; Phone Number: 86-13611093752; Email: 13611093752@163.com
• Study Contact Backup: Name: Jiarou Wang, MD; Phone Number: 86-13269163729; Email: ChristinaWang97@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Zhaohui Zhu, MD; Phone Number: 86-13611093752; Email: 13611093752@163.com
      • Contact: Jiarou Wang, MD; Phone Number: 86-13269163729; Email: ChristinaWang97@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LNC1011 Dose escalation; 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.	Drug: 177Lu-LNC1011; [177Lu]Lu-LNC1011 is a novel long-circulating PSMA therapeutic probe.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dosimetry of normal organs and tumors	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.	through study completion, an average of 4 weeks
Hematologic adverse events collection	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	through study completion, an average of 6 months
Liver and renal toxic events collection	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).	through study completion, an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA Response	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%.	through study completion, an average of 6 months
Pharmacokinetics and dosimetry	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.	Whole-body (WB) scans were performed at 2, 4, 24, 48, 72, 120, and 168 hours following intravenous administration of [177Lu]Lu-LNC1011

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Zhaohui Zhu, MD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: January 10, 2024
• First Submitted That Met QC Criteria: February 7, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Estimated): December 11, 2024
• Last Update Submitted That Met QC Criteria: December 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: mCRPC; PSMA; 177Lu
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: PUMCH-NM-PSMA1011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No