[Lu-177]Ludotadipep in Castration-resistant Prostate Cancer(CRPC): Investigation of Drug and Application

NCT05458544 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: FC705-US-1
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 4

Brief Summary

Phase 1: The objective of the Phase 1 part of the clinical trial is to verify safety and tolerability (dose-limiting toxicity \[DLT\], maximum tolerated dose \[MTD\]) of a single 3.7 Giga-Becquerel (GBq) dose with the potential for one dose level de-escalation to 2.775 GBq if necessary, to determine the recommended \[177Lu\]Ludotadipep dose for use in the Phase 2a part of the trial. Phase 2a: The objective of the Phase 2a part of the trial is to evaluate safety and efficacy for repeated administration of the recommended \[177Lu\]Ludotadipep dose. The Recommended Phase 2 dose (RP2D) will be based on the study results from the Phase 1 trial in South Korea upon consultation with the FDA.

Conditions

Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLT) with a single fixed dose of [177Lu]Ludotadipep during the first cycle (8 [±1] weeks) (Phase 1)

  Determination of Maximum Tolerated Dose (MTD)

  Single dose and 8 weeks follow up (Screening up to 28 days)

• Objective Response Rate (Phase 2a)

  Complete Response \[CR\] Rate + Partial Response \[PR\] Rate

  up to 40 weeks (4 to 6 doses at 8-weekly intervals [± 1 week], with 6 week follow-up after each dose (Screening up to 28 days)

Secondary Outcomes (10)

• Safety assessments (Phase 1)

  Single dose and 8 weeks follow up (Screening up to 28 days)

• Whole-body absorbed dose (Phase 1)

  Single dose and 8 weeks follow up (Screening up to 28 days)

• Biodistribution: assessment of the absorption (uptake) into the blood, lungs, liver, spleen, pancreas, kidneys, muscle, stomach, and tumor based on the level obtained from whole body scan (WBS) 2 hours, 24 hours, 48 hours, and 7 days post-dose (Phase 1)

  Single dose and 8 weeks follow up (Screening up to 28 days)

• Disease Control Rate (Phase 2a)

  up to 40 weeks (4 to 6 doses at 8-weekly intervals [± 1 week], with 6 week follow-up after each dose (Screening up to 28 days)

• Safety assessments (Phase 2a)

  up to 40 weeks (4 to 6 doses at 8-weekly intervals [± 1 week], with 6 week follow-up after each dose (Screening up to 28 days)

Study Arms (1)

[177Lu]Ludotadipep 3.7 GBq

EXPERIMENTAL

If investigators observed one or no DLT in 6 patients at the 3.7 GBq dose level, the study can advance to the Phase 2a part of the trial after the safety review committee (SRC) review.

Drug: [177Lu]Ludotadipep 3.7 GBq

Interventions

[177Lu]Ludotadipep 3.7 GBq DRUG

Phase 1: Patients will receive a single dose of 3.7 GBq of \[177Lu\]Ludotadipep * Test article code/name: \[177Lu\]Ludotadipep * Administration route: intravenous injection * Total dose strength: 3.7 GBq * Dosage form: solution for injection Phase 2a: Patients will receive 3.7 GBq of \[177Lu\]Ludotadipep every 8 \[±1\] weeks (4 to 6 times) * Test article code/name: \[177Lu\]Ludotadipep * Administration route: intravenous injection * Total dose strength: 4 to 6 x 3.7 GBq * Dosage form: solution for injection

[177Lu]Ludotadipep 3.7 GBq

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male and ≥ 18 years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the following criteria in order to be included in both the Phase 1 and Phase 2a parts of the trial:
• Male and ≥ 18 years
• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features at initial diagnosis
• Disease progression on any one of the following: prior enzalutamide, abiraterone, apalutamide or related agent therapy as defined by meeting at least one of the following criteria per the investigator in accordance with the Prostate Cancer Working Group 3 (PCWG3) criteria \[Scher et al, 2016\]:
• PSA progression as defined by a minimum of two rising PSA levels at least 1 week apart, ideally three successive measurements
• Soft tissue disease progression defined as \>20% increase in sum of diameters of all target lesions based on sum of diameters since treatment started or the appearance of 1 or more new lesions by RECIST 1.1
• Bone disease progression defined by two or more new lesions on bone scan
• Serum testosterone level \< 50 ng/dL (\< 0.5 ng/mL, \< 1.7 nmol/L). Patients may have ongoing androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) "super-agonist" or antagonist, and/or be surgically or medically castrated.
• Patients must have PSMA positive lesions. These are defined as having Ga 68-PSMA-11 uptake greater than that of liver parenchyma in one or more metastatic lesions of any size in any organ system. PSMA-negative lesions are defined as having PSMA uptake equal to or lower than that of liver parenchyma in any lymph node with a short axis of at least 2.5 cm, in any metastatic solid-organ lesions with a short axis of at least 1.0 cm, or in any metastatic bone lesion with a soft-tissue component of at least 1.0 cm in the short axis.
• Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks prior to Day 1
• Patients who have received a taxane or are ineligible or choose not to receive taxane-based chemotherapy based on personal preference or physician opinion. Examples of conditions that could make a patient ineligible or refuse to receive taxane-based chemotherapy include the following:
• Poor performance status
• Prior intolerance to cytotoxic agents
• Other serious medical conditions such as symptomatic peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher; or clinically significant cardiovascular disease per the Investigator
• ECOG PS of 0 to 2 for Phase 1 and 0 to 1 for Phase 2a

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria (applies to both Phase 1 and Phase 2a):
• Impaired organ function as evidenced by the following laboratory values at Screening:
• Absolute neutrophil count \< 1500/μL
• Platelet count \< 100,000/μL
• Hemoglobin \< 9.0 g/dL Note: the patient cannot have received blood transfusion or growth factor support in the 2 weeks prior to screening laboratory hematology assessments.
• Albumin \< 3.0 g/dL (30 g/L)
• Total bilirubin \> 2 x upper limit of normal (ULN) unless in instances of known or suspected Gilbert's disease
• aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 x ULN
• Calculated creatinine clearance \< 60 mL/min (Cockroft-Gault equation), or currently on renal dialysis
• QT interval corrected for heart rate (QTcF) \> 470 msec
• Sjogren's syndrome
• Known or suspected brain metastasis or active leptomeningeal disease
• History of other malignancy within the previous 3 years, except basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer
• History of active thromboembolism within the last 3 months of Day 1
• Serious persistent infection within 14 days prior to Day 1

Sponsors & Collaborators

• FutureChem: lead

Study Sites (4)

VA Greater Los Angeles Healthcare System,Cancer Center Research

Los Angeles, California, 90073, United States

RECRUITING

University of Maryland

Baltimore, Maryland, 20742, United States

NOT YET RECRUITING

Chesapeake Urology Research Associates

Towson, Maryland, 21144, United States

NOT YET RECRUITING

Pennsylvania Cancer Specialists & Research Institute (Formerly Gettysburg Cancer Center)

Gettysburg, Pennsylvania, 17325, United States

RECRUITING

Study Officials

• Arif Hussain, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chansoo Park, Ph.D

CONTACT

+82-70-5066-2479; chansoo.park@futurechem.co.kr

Jeffry Chen, MSc

CONTACT

+1-772-208-7044; jchen@linicalamericas.com

Study Design

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

Study Record Dates

• First Submitted: June 10, 2022
• First Posted: July 14, 2022
• Study Start: September 1, 2022
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: April 29, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)