177Lu-rhPSMA-10.1 for Prostate Cancer

Recruiting at 7 trial locations

Overseen By Blue Earth Therapeutics

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Blue Earth Therapeutics Ltd

Must be taking: LHRH or GnRH

Must not be taking: Bisphosphonates

Disqualifiers: CNS metastases, Haematological malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

82 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for prostate cancer that has spread and no longer responds to standard hormone treatments. The trial aims to determine the right dose, safety, and effectiveness of an injection called 177Lu-rhPSMA-10.1. Participants will receive the treatment in varying dosages to identify the most effective one. Men whose prostate cancer still appears on special scans and have experienced progression after other treatments may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that at least 4 weeks or 5 half-lives (whichever is longer) have passed since your last anti-cancer treatment before starting the study treatment, except for Luteinising Hormone-releasing Hormone or GnRH. This means you may need to stop some medications, but not all.

Is there any evidence suggesting that 177Lu-rhPSMA-10.1 injection is likely to be safe for humans?

Research has shown that 177Lu-rhPSMA-10.1 demonstrates promising safety results from earlier studies. Patients generally tolerated this treatment well, and no major safety issues were reported. Initial data suggest it delivers more radiation directly to cancer tumors than some other treatments, targeting cancer cells while minimizing harm to healthy ones. Overall, the evidence so far indicates that 177Lu-rhPSMA-10.1 is relatively safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about 177Lu-rhPSMA-10.1 for prostate cancer because it targets the prostate-specific membrane antigen (PSMA), a protein highly expressed in prostate cancer cells, allowing for precise delivery of radiation directly to the cancer cells. Unlike standard treatments like hormone therapy or chemotherapy, which can affect healthy cells, this approach minimizes damage to surrounding tissue. Additionally, the different dosing regimens in the trial aim to optimize treatment efficacy and tolerability, potentially offering more personalized options for patients depending on their specific needs.

What evidence suggests that 177Lu-rhPSMA-10.1 might be an effective treatment for prostate cancer?

Research shows that 177Lu-rhPSMA-10.1 is a promising treatment for prostate cancer, specifically targeting the PSMA protein on cancer cells. Early studies indicate that it delivers more radiation to cancer cells than to healthy ones, suggesting its effectiveness. Initial results suggest that patients tolerate it well and show encouraging early success. This trial will explore different dosing regimens of 177Lu-rhPSMA-10.1 across various cohorts. Evidence also suggests that combining it with other treatments, like cobimetinib, could enhance its effectiveness. Overall, these early findings are promising for patients with advanced prostate cancer expressing PSMA. ^{1 2 3 6 7}

Who Is on the Research Team?

Blue Earth Therapeutics

Principal Investigator

Blue Earth Therapeutics

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread, who are in fairly good health (able to perform daily activities) with a life expectancy of at least 6 months. They must have had no recent major surgeries or other cancer treatments, and their cancer should be visible on scans and produce a specific protein seen on PET/CT scans.

Inclusion Criteria

My side effects from previous treatments are mild, except for possible hair loss and some nerve issues or increased need to urinate.

Adequate contraception for patients and their partners

My blood tests show my organs and bone marrow are working well.

Exclusion Criteria

I have severe issues controlling my bladder that could make handling radioactive urine unsafe.

I have one kidney, a kidney transplant, or am on medication that could harm my kidneys.

I have had specific radiation treatments for my cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive 177Lu-rhPSMA-10.1 with dose-finding and dosimetry components

Up to 18 weeks

3 cycles

Phase 2 Treatment

Participants receive Lutetium (177Lu) rhPSMA-10.1 with efficacy and safety assessments

Up to 48 weeks

6-8 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-rhPSMA-10.1 injection

Trial Overview The trial is testing the safety and effectiveness of an injection called 177Lu-rhPSMA-10.1 for men whose prostate cancer can be seen on certain scans and continues to grow despite hormone therapy. The study will also determine the right dose and measure how the body processes the drug.

How Is the Trial Designed?

Group I: Phase 2, Cohort 2C (optional) Experimental Treatment 1 Intervention

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 II: Phase 2, Cohort 2B Experimental Treatment 1 Intervention

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 III: Phase 2, Cohort 2A Experimental Treatment 1 Intervention

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 IV: Phase 1, Cohort B Experimental Treatment 2 Interventions

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

Group V: Phase 1, Cohort A Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Blue Earth Therapeutics Ltd

Lead Sponsor

Trials

2

Recruited

110+

PSI CRO

Industry Sponsor

Trials

13

Recruited

2,800+

Published Research Related to This Trial

The novel radiopharmaceutical 177Lu-rhPSMA-10.1 delivers a significantly higher absorbed radiation dose to tumor lesions compared to 177Lu-PSMA-I&T, with an average increase of 3.3 times, which could enhance treatment efficacy for metastatic castration-resistant prostate cancer.

While 177Lu-rhPSMA-10.1 results in a higher radiation dose to the kidneys, it also improves the therapeutic index (TI) by 1.1 to 3.1 times, allowing for better management of tumor doses while minimizing kidney exposure, which is crucial for patients with longer life expectancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Intrapatient Dosimetry Comparison of 177Lu-rhPSMA-10.1 and 177Lu-PSMA-I&T in Patients with Metastatic Castration-Resistant Prostate Cancer. Rinscheid, A., Gäble, A., Wienand, G., et al.[2023]

The study compared various PSMA-targeted radiohybrid ligands, revealing that [177Lu]Lu-rhPSMA-10.1 had the best pharmacokinetics, showing low kidney uptake and high tumor accumulation in mouse models.

[177Lu]Lu-rhPSMA-10.1 demonstrated favorable properties for potential clinical use, suggesting it could provide effective tumor targeting while minimizing damage to healthy tissues, particularly the kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and Preclinical Evaluation of 177Lu-Labeled Radiohybrid PSMA Ligands for Endoradiotherapy of Prostate Cancer. Wurzer, A., Kunert, JP., Fischer, S., et al.[2023]

The maximum tolerated dose (MTD) of [177Lu]Lu-LNC1003 for treating metastatic castration-resistant prostate cancer was determined to be 1.85 GBq, with doses of 1.11 and 1.85 GBq per cycle being well tolerated by patients.

The treatment showed promising efficacy, with a PSA decline observed in a significant number of patients, particularly at the 1.85 GBq dose level, indicating potential therapeutic benefits for patients with bone and lymph node metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 trial to determine the maximum tolerated dose and patient-specific dosimetry of [177Lu]Lu-LNC1003 in patients with metastatic castration-resistant prostate cancer. Zang, J., Wang, G., Zhao, T., et al.[2023]

In a study of 54 patients with advanced metastatic castration-resistant prostate cancer (mCRPC), 79% showed a significant decrease in PSA levels after three cycles of [177Lu]Lu-PSMA-617 radio-ligand therapy, indicating a strong therapeutic response.

The treatment was well-tolerated, with a median overall survival of 119 weeks and a median progression-free survival of 25 weeks, suggesting that PSMA-RLT can be an effective option for patients with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks. Rasul, S., Hacker, M., Kretschmer-Chott, E., et al.[2021]

177 Lu-rhPSMA-10.1 is a new radiopharmaceutical designed to target PSMA, showing promise in treating metastatic castrate-resistant prostate cancer, particularly in patients who have not responded to previous therapies.

In a case study of an 86-year-old man, switching to 177 Lu-rhPSMA-10.1 after initial treatment failure led to a renewed tumor response, suggesting its potential efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177 Lu-rhPSMA-10.1 Induces Tumor Response in a Patient With mCRPC After PSMA-Directed Radioligand Therapy With 177 Lu-PSMA-I&T. Bundschuh, RA., Pfob, CH., Wienand, G., et al.[2023]

The preclinical study demonstrated that 19F/177Lu-rhPSMA-7.3 has significantly higher tumor uptake and retention compared to the established treatment 177Lu-PSMA I&T, suggesting it may be more effective for targeting prostate cancer.

In terms of safety, 19F/177Lu-rhPSMA-7.3 showed similar clearance kinetics and radiation doses to healthy organs as 177Lu-PSMA I&T, while providing a greater reduction in tumor size and improved survival rates in treated mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Preclinical Biodistribution, Dosimetry, and Endoradiotherapy in Metastatic Castration-Resistant Prostate Cancer Using 19F/177Lu-rhPSMA-7.3 and 177Lu-PSMA I&T. Yusufi, N., Wurzer, A., Herz, M., et al.[2022]

In a study involving six patients with metastatic castration-resistant prostate cancer, 177Lu-rhPSMA-7.3 demonstrated significantly higher tumor uptake compared to 177Lu-PSMA I&T, with absorbed doses to tumors being 2-3 times greater for rhPSMA-7.3.

Despite higher absorbed doses to normal organs with 177Lu-rhPSMA-7.3, the therapeutic index (TI) for both radiopharmaceuticals was similar, suggesting that rhPSMA-7.3 could provide effective treatment with potentially lower injected activity, enhancing radiation safety for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretherapeutic Comparative Dosimetry of 177Lu-rhPSMA-7.3 and 177Lu-PSMA I&T in Patients with Metastatic Castration-Resistant Prostate Cancer. Feuerecker, B., Chantadisai, M., Allmann, A., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40049746/

Preclinical Evaluation of 177 Lu-rhPSMA-10.1, a ... 177 Lu-rhPSMA-10.1 is a novel radiohybrid prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy for prostate cancer.

2. jnm.snmjournals.org jnm.snmjournals.org/content/66/4/599

Preclinical Evaluation of 177 Lu-rhPSMA-10.1, a ... 177 Lu-rhPSMA-10.1 is a novel radiohybrid prostate-specific membrane antigen (PSMA)–targeted radiopharmaceutical therapy for prostate cancer.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38164586/

First Safety and Efficacy Data with the Radiohybrid 177Lu- ... Conclusion: 177Lu-rhPSMA-10.1 demonstrated encouraging preliminary efficacy and was well tolerated. Formal clinical trials are now under way to ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0969805125000514

A novel synergistic drug combination of a mitogen ... The combination of cobimetinib and [ 177 Lu]Lu-rhPSMA-10.1 demonstrated enhanced preclinical therapeutic efficacy versus single agents.

5. onclive.com onclive.com/view/177lu-rhpsma-10-1-injection-generates-favorable-radiation-dosimetry-data-in-mcrpc

177Lu rhPSMA-10.1 Injection Generates Favorable ... 177Lu rhPSMA-10.1 injection led to proportionally higher absorbed radiation doses in tumors vs healthy tissues in patients with mCRPC.

6. urotoday.com urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/162237-blue-earth-therapeutics-initiates-phase-2-clinical-trial-evaluating-the-efficacy-and-safety-of-lutetium-177lu-rhpsma-10-1-injection-in-metastatic-castrate-resistant-prostate-cance.html

Blue Earth Therapeutics Initiates Phase 2 Clinical Trial ... (177Lu) rhPSMA-10.1 injection, engineered to improve delivery of radiation to cancer lesions, recently showed promising data in a phase 1 ...

7. jnm.snmjournals.org jnm.snmjournals.org/content/65/3/432

First Safety and Efficacy Data with the Radiohybrid 177Lu ... 177 Lu-rhPSMA-10.1 delivers an increased radiation dose to the tumor compared with 177 Lu-PSMA-I&T, reaching an up to 8-fold improvement in tumor dose in one ...