Anti-tumour Activity of (177Lu) rhPSMA-10.1 Injection

NCT ID: NCT05413850

Last Updated: 2026-01-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

82 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-20

Study Completion Date

2028-03-31

Brief Summary

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To determine the dose, safety, radiation dosimetry and efficacy of 177Lu-rhPSMA-10.1 in participants with PSMA-expressing metastatic castrate resistant prostate cancer.

Detailed Description

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This is an interventional, open-label, integrated Phase 1 \& 2 study to assess the safety, tolerability, radiation dosing regimen and anti-tumour activity of Lutetium (177Lu) rhPSMA-10.1 (IMP) in men with metastatic castrate-resistant prostate cancer (mCRPC). The study will consist of 2 parts: a non-randomised Phase 1 part, with safety, dose-finding, and dosimetry components, and a randomised Phase 2 part, with efficacy and safety assessments, and testing dosing regimens selected following analysis of the safety and dosimetry data in Phase 1. Both phases will include subjects with prostate-specific membrane antigen (PSMA)-positive mCRPC, which has progressed following prior therapy. Phase 1 will include a post-chemotherapy mCRPC cohort of subjects who have experienced disease progression on or after at least 1 novel androgen axis drug (NAAD) (e.g. abiraterone, enzalutamide) and at least 1 course (but no more than 2 courses) of taxane-based chemotherapy. Phase 2 will include subjects who have experienced disease progression on or after at least 1 NAAD (e.g. abiraterone, enzalutamide, apalutamide, darolutamide) but have not received previous taxane-based chemotherapy for the treatment of mCRPC.

Conditions

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Prostate Cancer Metastatic Castration-resistant Prostate Cancer mCRPC Urogenital Neoplasms Prostatic Neoplasms Prostatic Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Non Randomized (Phase 1) and Randomized (Phase 2)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1, Cohort A

Subjects with PSMA positive disease will receive 5.55GBq of 177Lu-rhPSMA-10.1 (maximum of 3 cycles).

Group Type EXPERIMENTAL

Lutetium (177Lu) rhPSMA-10.1 Injection

Intervention Type DRUG

Therapeutic cycles of 177Lu-rhPSMA-10.1

18F-rhPSMA-7.3 injection (in phase 1 only)

Intervention Type DIAGNOSTIC_TEST

18F-rhPSMA-7.3 (in phase 1 only) at an administered activity of 296 MBq (8 mCi) for PET/CT scan to ascertain whether the subject has PSMA-positive disease.

Phase 1, Cohort B

Subjects with PSMA positive disease will receive 7.4GBq of 177Lu-rhPSMA-10.1 (maximum of 3 cycles).

Group Type EXPERIMENTAL

Lutetium (177Lu) rhPSMA-10.1 Injection

Intervention Type DRUG

Therapeutic cycles of 177Lu-rhPSMA-10.1

18F-rhPSMA-7.3 injection (in phase 1 only)

Intervention Type DIAGNOSTIC_TEST

18F-rhPSMA-7.3 (in phase 1 only) at an administered activity of 296 MBq (8 mCi) for PET/CT scan to ascertain whether the subject has PSMA-positive disease.

Phase 2, Cohort 2A

Subjects with PSMA positive disease will receive 2 doses at 10.00 GBq (270 mCi) followed by up to 5 additional doses at 7.40 GBq (200 mCi), all doses administered at 6-weekly intervals.

Group Type EXPERIMENTAL

Lutetium (177Lu) rhPSMA-10.1 Injection

Intervention Type DRUG

Therapeutic cycles of 177Lu-rhPSMA-10.1

Phase 2, Cohort 2B

Subjects with PSMA positive disease will receive up to 8 doses at 7.40 GBq (200 mCi). The first 3 doses will be administered at 3-weekly intervals, with the remaining doses being administered at 6-weekly intervals.

Group Type EXPERIMENTAL

Lutetium (177Lu) rhPSMA-10.1 Injection

Intervention Type DRUG

Therapeutic cycles of 177Lu-rhPSMA-10.1

Phase 2, Cohort 2C (optional)

If opened, subjects with PSMA positive disease will receive 2 doses at 14.80 GBq (400 mCi) followed by up to 4 additional doses at 7.40 GBq (200 mCi), all doses administered at 6-weekly intervals.

Group Type EXPERIMENTAL

Lutetium (177Lu) rhPSMA-10.1 Injection

Intervention Type DRUG

Therapeutic cycles of 177Lu-rhPSMA-10.1

Interventions

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Lutetium (177Lu) rhPSMA-10.1 Injection

Therapeutic cycles of 177Lu-rhPSMA-10.1

Intervention Type DRUG

18F-rhPSMA-7.3 injection (in phase 1 only)

18F-rhPSMA-7.3 (in phase 1 only) at an administered activity of 296 MBq (8 mCi) for PET/CT scan to ascertain whether the subject has PSMA-positive disease.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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177Lu-rhPSMA-10.1 18F-rhPSMA-7.3 (in phase 1 only)

Eligibility Criteria

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Inclusion Criteria

1. Male subjects, 18 years of age or older with histologically confirmed adenocarcinoma of the prostate.
2. Serum testosterone levels \<50 ng/dL (1.73 nmol/L) after surgical or continued chemical castration.
3. Presence of disease target or non target lesions (per RECIST v1.1) on CT/MRI and/or presence of disease on full body 99mTc bone scan performed within 28 days of screening.
4. Positive disease expression of PSMA as confirmed on PSMA PET/CT scan.
5. At least 4 weeks or 5 half-lives (whichever is longer) elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinising Hormone-releasing Hormone or GnRH).
6. Resolution of all previous treatment related toxicities to CTCAE version 5.0 grade of ≤1 (except for chemotherapy induced alopecia and grade 2 peripheral neuropathy or grade 2 urinary frequency which are allowed).
7. Prior major surgery must be at least 12 weeks prior to study entry.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with a life expectancy ≥6 months.
9. Adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline.
10. Adequate contraception for patients and their partners.
11. For Phase 1 mCRPC only: Subjects who have experienced disease progression on or after at least 1 NAAD (e.g. abiraterone, enzalutamide) and at least 1 course (but no more than 2 courses) of taxane-based chemotherapy. For Phase 2 mCRPC only: Subjects who have experienced disease progression on or after at least 1 NAAD (e.g. abiraterone, enzalutamide, apalutamide, darolutamide), but have not received previous taxane-based chemotherapy for the treatment of mCRPC.

Exclusion Criteria

1. Known hypersensitivity to the therapeutic or diagnostic IMP or any of its constituents.
2. Presence of significant PSMA-negative disease on ceCT/MRI scan
3. Diffuse marrow infiltration of disease ('superscan' appearance on full body 99mTc bone scan).
4. Symptomatic spinal cord compression, or clinical or radiological findings that are indicative of impending spinal cord compression.
5. Known history of haematological malignancy.
6. Known history of central nervous system (CNS) metastases.
7. Histological findings consistent with neuroendocrine phenotype of prostate cancer.
8. Known history of other solid malignancy that may reduce life expectancy and/or may interfere with disease assessment.
9. Unresolved urinary tract obstruction defined as radiographic evidence of hydronephrosis with or without ureteric stent/nephrostomy.
10. Any uncontrolled significant medical, psychiatric, or surgical condition or laboratory finding that would pose a risk to subject safety or interfere with study participation or interpretation of individual subject results.
11. Ongoing treatment with bisphosphonates for bone-targeted therapy.
12. Severe urinary incontinence that would preclude safe disposal of radioactive urine.
13. Single kidney or renal transplant or any concomitant nephrotoxic therapy that might put the subject at high risk of renal toxicity during the study in the judgement of the investigator.
14. Clinically significant abnormalities on a single 12 lead electrocardiogram (ECG) at screening.
15. Previously received external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys.
16. Previous treatment with any of the following: PSMA targeted radionuclide therapy, Strontium-89, Samarium-153, Rhenium 186, Rhenium-188, Radium-223, hemi-body irradiation.
17. Subjects with bilateral hip replacements or any significant metallic implants or objects, that may affect image quality and/or dosimetry calculations.
18. Transfusion of blood products for the sole purpose of meeting the eligibility criteria for this clinical study.
19. Participation in other studies involving IMP(s) within 28 days or 5 half-lives (whichever is longer) prior to study entry and/or during study participation.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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PSI CRO

INDUSTRY

Sponsor Role collaborator

Blue Earth Therapeutics Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Blue Earth Therapeutics

Role: STUDY_DIRECTOR

Blue Earth Therapeutics

Locations

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Biogenix Molecular LLC

Miami, Florida, United States

Site Status RECRUITING

Emory University Hospital

Atlanta, Georgia, United States

Site Status RECRUITING

XCancer Omaha / Urology Cancer Center

Omaha, Nebraska, United States

Site Status RECRUITING

Weill Cornell Medicine - New York - Presbyterian Hospital

New York, New York, United States

Site Status COMPLETED

Jules Bordet Institute

Brussels, , Belgium

Site Status RECRUITING

Saint Luc University Hospital

Brussels, , Belgium

Site Status RECRUITING

University Hospital Ghent

Ghent, , Belgium

Site Status RECRUITING

University Hospital Center Sart-Tilman

Liège, , Belgium

Site Status RECRUITING

Radboud UMC

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Bristol Hematology and Oncology Center

Bristol, , United Kingdom

Site Status RECRUITING

Beatson West of Scotland Cancer Center

Glasgow, , United Kingdom

Site Status RECRUITING

St Bartholomew's Hospital

London, , United Kingdom

Site Status RECRUITING

James Cook University Hospital

Middlesbrough, , United Kingdom

Site Status RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Site Status RECRUITING

Countries

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United States Belgium Netherlands United Kingdom

Central Contacts

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Blue Earth Therapeutics

Role: CONTACT

+44 (0)1865 634500

Facility Contacts

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Jerry Joseph

Role: primary

786-791-1799

David Michael Schuster

Role: primary

404-778-5625

Nashwa Jarkas

Role: backup

404-727-2193

Nordquist

Role: primary

402-991-8468

Carlos Artigas Guix

Role: primary

+32 (02) 541 3082

Emmanuel Seront

Role: primary

+32 (2764) 51 06

Charles van Praet

Role: primary

+32 (9) 332 1955

Nadia Withofs

Role: primary

+32 (42) 844 362

Nagarajah, MD

Role: primary

Amarnath Challapalli, MD

Role: primary

+11 (7342) 2418

David Colville

Role: primary

+44 (07999) 331 565

Kenrick Ng, MD

Role: primary

+44 (079) 2869 3663

Darren Leaning, MD

Role: primary

+44 (016) 4285 0850

Simon Crabb, MD

Role: primary

+40 (2381) 205 170

References

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Dierks A, Gable A, Rinscheid A, Wienand G, Pfob CH, Kircher M, Enke JS, Janzen T, Patt M, Trepel M, Weckermann D, Bundschuh RA, Lapa C. First Safety and Efficacy Data with the Radiohybrid 177Lu-rhPSMA-10.1 for the Treatment of Metastatic Prostate Cancer. J Nucl Med. 2024 Mar 1;65(3):432-437. doi: 10.2967/jnumed.123.266741.

Reference Type DERIVED
PMID: 38164586 (View on PubMed)

Related Links

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Other Identifiers

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BET-PSMA-121

Identifier Type: -

Identifier Source: org_study_id

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