177Lu-rhPSMA-10.1 for Prostate Cancer

Recruiting at5 trial locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial tests a new radioactive treatment for men with advanced prostate cancer that doesn't respond to hormone therapy. The treatment targets and kills cancer cells by delivering radiation directly to them. This new approach has shown promise in extending survival for men with advanced prostate cancer.

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.

What data supports the effectiveness of the treatment 177Lu-rhPSMA-10.1 for prostate cancer?

Research shows that 177Lu-rhPSMA-10.1 can significantly increase the radiation dose absorbed by tumors compared to a similar treatment, 177Lu-PSMA-I&T, leading to a better tumor response in patients with advanced prostate cancer. ^{1 2 3 4 5}

What makes the drug 177Lu-rhPSMA-10.1 unique for prostate cancer treatment?

177Lu-rhPSMA-10.1 is a novel drug that targets prostate-specific membrane antigen (PSMA) and delivers a higher radiation dose directly to prostate cancer tumors compared to similar treatments, potentially improving effectiveness. It also has optimized pharmacological properties that may reduce radiation exposure to healthy organs, making it a promising option for patients with metastatic castration-resistant prostate cancer. ^{1 2 4 6 7}

Research Team

Blue Earth Therapeutics

Principal Investigator

Blue Earth Therapeutics

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• 177Lu-rhPSMA-10.1 injection (Radioisotope Therapy)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

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]

References

1. United States 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. [2022]

2. United States 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. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks. [2021]

4. United States 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. [2023]

5. Germany 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. [2023]

6. United States 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. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Synthesis and Preclinical Evaluation of 177Lu-Labeled Radiohybrid PSMA Ligands for Endoradiotherapy of Prostate Cancer. [2023]