The Safety and Dosimetry Study of 177Lu-LNC1003 Injection

NCT06237491 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: 177Lu-LNC1003-001
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

This proposal is a phase I, open-label study of a 3-Dose Regimen of Escalating Doses of 177Lu-LNC1003 Injection in patients with PSMA-positive mCRPC. In the clinical development, we aim to demonstrate the following:

1. 1.Determination of the therapeutic dose(s) to be used in the expansion phase.
2. 2.Demonstration of the safety and tolerability of 177Lu-LNC1003 at therapeutic doses.

Conditions

Metastatic Castration-resistant Prostate Cancer, mCRPC

Outcome Measures

Primary Outcomes (3)

• the safety of 177Lu-LNC1003 Injection

  To evaluate the safety of 177Lu-LNC1003 Injection assessed from the number of patients with treatment-related adverse events using CTCAE v5.0.

  through study completion, assessed up to 2 years.

• To identify the dose-limiting toxicities (DLTs)

  To identify DLTs of escalating doses of 177Lu-LNC1003 Injection up to 70 mCi (2.59 GBq) administered intravenously to patients in their first cycle of 6 weeks.

  through cycle 1, an average of 6 weeks

• To determine if the MTD is among the explored dose levels and identify the expansion phase dose

  To determine if the maximum tolerated dose is among the explored dose levels and identify the recommended expansion phase dose of 177Lu-LNC1003 Injection.

  Through study completion, assessed up to 2 years

Study Arms (3)

Experimental: 177Lu-LNC1003 Injection group 1

EXPERIMENTAL

177Lu-LNC1003 Injection, a single dose of 30mCi will be administered every 6 weeks, for a total of 2 cycles. Interventions: Drug: 177Lu-LNC1003 Injection group 1 radionuclide therapy

Drug: 177Lu-LNC1003 Injection group 1

Experimental: 177Lu-LNC1003 Injection group 2

EXPERIMENTAL

177Lu-LNC1003 Injection, a single dose of 50mCi will be administered every 6 weeks, for a total of 2 cycles. Interventions: Drug: 177Lu-LNC1003 Injection group 2 radionuclide therapy

Drug: 177Lu-LNC1003 Injection group 2

Experimental: 177Lu-LNC1003 Injection group 3

EXPERIMENTAL

177Lu-LNC1003 Injection, a single dose of 70mCi will be administered every 6 weeks, for a total of 2 cycles. Interventions: Drug: 177Lu-LNC1003 Injection group 3 radionuclide therapy

Drug: 177Lu-LNC1003 Injection group 3

Interventions

177Lu-LNC1003 Injection group 1 DRUG

The treatment regimen will consist of a single dose 30 mCi intravenous administration of 177Lu-LNC1004 Injection per 6-week cycle, for a total of 2 cycles, the dose per cycle will be fixed.

Experimental: 177Lu-LNC1003 Injection group 1

177Lu-LNC1003 Injection group 2 DRUG

The treatment regimen will consist of a single dose 50 mCi intravenous administration of 177Lu-LNC1004 Injection per 6-week cycle, for a total of 2 cycles, the dose per cycle will be fixed.

Experimental: 177Lu-LNC1003 Injection group 2

177Lu-LNC1003 Injection group 3 DRUG

The treatment regimen will consist of a single dose 70 mCi intravenous administration of 177Lu-LNC1004 Injection per 6-week cycle, for a total of 2 cycles, the dose per cycle will be fixed.

Experimental: 177Lu-LNC1003 Injection group 3

Eligibility Criteria

• Age: 21 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients or authorized guardians must have the ability to understand and sign an approved informed consent form (ICF).
• Patients must have the ability to understand and comply with all protocol requirements.
• Patients must be aged 21 years or older.
• Patients must have histological, pathological, and/or cytological confirmation of PC that is refractory to or has progressed following prior treatments.
• Patients must have ≥ 1 metastatic lesion present on baseline and documented progressive mCRPC based on the Prostate Cancer Working Group 3 (PCWG3) criteria; patients must fill at least one of the following criteria:
• PSA progression
• Objective radiographic progression in soft tissue
• New bone lesions
• Patients must have a castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L).
• Patients must have received treatment with at least one prior novel androgen receptor pathway inhibitor (such as enzalutamide, apalutamide, and/or abiraterone).
• Patients must have been deemed not suitable for chemotherapy, i.e., the patient refused chemotherapy or was judged unsuitable for chemotherapy by the doctor. Alternatively, patients may have been previously treated with at least one, but no more than two previous taxane regimens, or have been offered, but declined, or been ineligible for taxane-based chemotherapy. A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a patient has received only one taxane regimen, the patient is eligible if:
• a. The patient\'s physician deems him unsuitable to receive a second taxane regimen (e.g., frailty assessed by geriatric or health status evaluation, intolerance, etc.).
• Patients must have at least 1 measurable lesion as defined by Response Criteria in Solid Tumors (RECIST) version 1.1.
• Patients must be 68Ga-PSMA-11 PET/CT scan positive.
• Patients must have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.

You may not qualify if:

• Other identified malignancies within 5 years in addition to radically treated locally curable malignant tumors, such as basal or squamous cell skin cancer, superficial bladder cancer.
• Previous treatment with any of the following within 6 months before enrollment: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation, 177Lu-PSMA-617 (Pluvicto) and any investigational beta-emitting radiotherapeutics.
• Any systemic anti-cancer therapy (e.g. PSMA-targeted radioligand therapy, chemotherapy, immunotherapy or biological therapy \[including monoclonal antibodies\]) within 28 days prior to day of enrollment
• Any investigational agents within 28 days of enrollment
• Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-LNC1003 as assessed from medical records
• Participants who have not fully recovered from major surgery or significant traumatic injury prior to the first dose of study drug or expects to have major surgery during the study period or within 3 months after the last dose of study drug
• Life expectancy \< 6 months as assessed by the treating physician
• Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
• A superscan; i.e., very high ratio of bone to background uptake due to high osteoblastic activity, as seen in the baseline Tc-99m diphosphonate bone scan.
• Clinically significant abnormalities on electrocardiogram (ECG) at screening including QTcF \> 470 ms, and subjects who cannot tolerate high volume load.
• Active and clinically significant bacterial, fungal, or viral infections, including hepatitis B (HBV), hepatitis C (HCV), know human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness (patients with treated HIV and hepatitis B or C could be included)
• Known brain metastases and/or carcinomatous meningitis, unless these metastases have been treated and stabilized
• Uncontrolled diabetes mellitus as defined by a HbA1c \> 9%
• Prior external beam radiation therapy involving \> 25% of the bone marrow

Sponsors & Collaborators

• Yantai LNC Biotechnology Singapore PTE. LTD.: lead

Central Study Contacts

A/Prof. Edmund Chiong

CONTACT

6908 2222

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2024
• First Posted: February 1, 2024
• Study Start: May 7, 2025
• Primary Completion: November 7, 2025
• Study Completion: December 17, 2025
• Last Updated: July 24, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share