177Lu-DOTA-TLX591 Safety, Biodistribution and Dosimetry Study

NCT04786847 | Completed Phase 1

• 1 other identifier: 177Lu-TLX591-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1 trial of TLX591, a monoclonal antibody HuX591 conjugated with a DOTA chelator and radiolabelled with 177Lu (177Lu-DOTA-TLX591). TLX591 is being developed as a PSMA-targeting antibody to be radiolabelled with a therapeutic radiosotope for the treatment of PSMA-expressing tumours, therefore this study has been designed to assess the safety and tolerability, pharmacokinetics, whole body biodistribution and radiation dosimetry of 177Lu-DOTA-TLX591.

Conditions

Metastatic Prostate Cancer

Keywords

prostate cancer; biodistribution; 177Lu-DOTA-TLX591; pharmacokinetics; dosimetery; safety; preliminary efficacy; standard of care; gallium-68 labeled PSMA-11 (68Ga-PSMA-11) PET/CT scan; novel androgen axis drug

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  To monitor the safety and tolerability of molecularly targeted radiotherapy with 177Lu-DOTA-TLX591, administered in two cycles in combination with best SoC in patients with PSMA-expressing metastatic castrate resistant prostate cancer. Treatment emergent adverse events (TEAE) will be classified according to MedDRA (Medical Dictionary for Regulatory Activities), frequency, severity according to NCI CTCAE V5.0, seriousness, and relationship of study treatment will be assessed. Laboratory abnormalities will be assessed according to the NCI CTCAE v.5.0.

  Day 1 to 5 years

Secondary Outcomes (2)

• Whole body and organ uptake of 177Lu-DOTA-TLX591

  Day 1 to Day 15

• Compare the whole body and organ uptake of 177Lu-TLX591 and 68Ga-PSMA-11 radioactive tracers

  Day 1 to 15

Study Arms (1)

Single administration of 177Lu-DOTA-TLX591

EXPERIMENTAL

Two single IV infusions of 76 mCi (2.8 GBq) each (equivalent to a 45 mCi/m2 administered activity in a standard 1.7m2 individual) of 177Lu-DOTA-TLX591, given 14 days apart. This therapy will be administered with the current standard of care treatment regimens.

Biological: 177Lu-DOTA-TLX591

Interventions

177Lu-DOTA-TLX591 BIOLOGICAL

TLX591, a monoclonal antibody HuX591 conjugated with a DOTA chelator and radiolabelled with 177Lu (177Lu-TLX591)

Single administration of 177Lu-DOTA-TLX591

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be male, at least 18 years old, with histologically/pathologically confirmed metastatic adenocarcinoma.
• Be of ECOG Performance Status 0, 1, or 2 and have an estimated life expectancy of ≥ 6 months.
• Have metastatic disease (≥1 metastatic lesions present on baseline whole body CT, MRI, or bone scintigraphy).
• Have castration-resistant PC (defined as disease progressing despite castration by orchiectomy or ongoing use of luteinizing hormone-releasing hormone \[LHRH\] agonists) and must have a castrate level of serum/plasma testosterone (\< 50 ng/dL or \<1.7 nmol/L).
• In the mCRPC setting, must have received a minimum of 12 weeks of prior therapy with a NAAD, either enzalutamide or abiraterone plus prednisone.
• Have received one line of prior taxane therapy, or have refused or are ineligible for taxanes
• Have disease that is progressing at study entry, despite a castrate testosterone level (\<50 ng/dL or \<1.7 nmol/L), by the demonstration of at least one of the following:
• Increase in PSA greater than 25% and \> 2 ng/mL above nadir, confirmed by progression at 2 timepoints at least 3 weeks apart.
• Progressive disease or new lesion(s) (relative to previous imaging) in the viscera or lymph nodes as per RECIST1.1 or in bone as per Prostate Cancer Working Group 3 \[PCWG3). Any ambiguous results are to be confirmed by additional imaging modality (e.g., CT, Tc-99m bone scintigraphy)
• Have disease which is PSMA positive, as demonstrated by a 68Ga-PSMA-11 PET/CT or \[18F\]DCFPyL PET/CT scan and confirmed as eligible by local reader (patient must have at least one site of metastatic disease with SUVmax ≥1.5 times the SUV of normal liver). If the disease meets the criteria for PSMA positivity, but there is one or more soft tissue lesion of ≥2 cm that is not PSMA positive, then the patient is to be excluded on the grounds that there is substantial disease which might not respond to the therapy.
• Must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e., surgery, local radiotherapy, NAAD, chemotherapy, etc.).
• Can be receiving a bisphosphonate or denosumab regimen provided tolerance to this therapy has been proven.
• \. Have adequate organ function at Screening:
• a. Bone marrow: i. Platelets ≥150×109/L ii. Absolute neutrophil count \>1.5×109/L iii. Hemoglobin ≥10g/dL (no red blood cell transfusion in the previous 4 weeks) b. Liver function: i. Total bilirubin ≤1.5×the upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3×ULN is permitted ii. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3×ULN OR ≤5×ULN for patients with liver metastases c. Renal function: i. Serum/plasma creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min
• Have the capacity to understand the study and be able and willing to comply with all protocol requirements.

You may not qualify if:

• Are unable, in the opinion of the Investigator, to understand or are unwilling to sign a written informed consent document or to follow investigational procedures.
• Have PC with pathological findings consistent with small cell or any histology other than adenocarcinoma of the prostate. If there are minor elements of neuroendocrine histology, this is acceptable.
• Experiencing uncontrolled pain
• Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with a prior history of malignancy that has been adequately treated and who have been disease-free for more than 3 years are eligible, as are patients with adequately treated non-melanoma skin cancer, and superficial bladder cancer.
• At increased risk of hemorrhage, or with a recent history of a thrombotic event (e.g., deep vein thrombosis \[DVT\]/ pulmonary embolism \[PE\]) and/or are using long-term anti-coagulant or anti-platelet agents.
• Have received prior administration of monoclonal antibody (mAb) J591 or HuJ591 or any other PSMA targeted therapy.
• Have known allergies, hypersensitivity, or intolerance to the investigational drug or its excipients.
• Have received systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy, or biological therapy) and/or radiation therapy within 4 weeks of enrollment OR if any significant AEs have not resolved to National Cancer Institute (NCI) AE Criteria ≤2; OR are receiving other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
• Have received prior treatment with radiopharmaceuticals containing, but not limited to, the following radioisotopes: 89Strontium, 153Samarium, 186Rhenium, 188Rhenium, 223Radium; or have received hemi-body irradiation within 6 months prior to randomization.
• Have received other investigational agents within 4 weeks of randomization.
• Have known brain metastases (any size) or hepatic metastases \> 1 cm.
• Have a history of seizure and/or stroke within past 6 months.
• Have clinical or radiologic findings indicative of impending cord compression or experiencing symptomatic cord compression.
• Have a serious active or sub-clinical infection, or angina pectoris or heart failure (New York Heart Association \[NYHA\] Class III or IV), significantly prolonged QT interval or other serious illness(es) involving the cardiac, respiratory, central nervous, renal, hepatic or hematological organ systems, which might impair the ability to complete this study or could interfere with determination of causality of any adverse effects experienced in this study, or which require treatment that could interact with study treatment.
• Have received treatment with any PARP inhibitors (i.e., Olaparib) or with any platinum based anti-neoplastic drugs.

Sponsors & Collaborators

• Telix Pharmaceuticals (Innovations) Pty Limited: lead

Study Sites (3)

GenesisCare Newcastle

Newcastle, Gateshead, 2290, Australia

Location

Diagnostic Nuclear Imaging at Hollywood Private Hospital

Perth, Western Australia, 6009, Australia

Location

GenesisCare SJOg Medical Centre,Murdoch

Perth, Western Australia, 6150, Australia

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Design

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

Model Details: Approximately 50 eligible patients will be enrolled and evaluated for safety and tolerability as well as undergo imaging to allow determination of the biodistribution and dosimetry 177Lu-DOTA-TLX591. Twenty-five patients will also be enrolled in a biodistribution and dosimetry sub-study, involving the collection of quantitative single-photon emission computerized tomography (SPECT) or single-photon emission computerized tomography/computerized tomography (SPECT/CT) data in a subset of patients.

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 8, 2021
• Study Start: January 30, 2022
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2023
• Last Updated: February 12, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)