177Lu rhPSMA-10.1 +/- Hormone Therapy for Prostate Cancer

Overseen By Marisa Lozano

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Tenofovir, Corticosteroids, others

Disqualifiers: Cardiovascular disease, Other malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

36 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if the proposed dose of 177Lu rhPSMA-10.1 is safe. Phase 2 will open if the Phase 1 dose is found to be safe. To learn about the safety and effects of 177Lu rhPSMA-10.1 alone and with androgen deprivation therapy (ADT) on patients with high-risk, localized prostate cancer before they have surgery to remove the disease.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on certain hormone therapies and systemic corticosteroids. It's best to discuss your specific medications with the trial team.

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

Research shows that 177Lu rhPSMA-10.1 can induce a positive tumor response in patients with advanced prostate cancer, especially after other similar treatments have stopped working. In one case, a patient with prostate cancer showed renewed tumor response after switching to 177Lu rhPSMA-10.1, suggesting its potential effectiveness. ^{1 2 3 4 5}

Is 177Lu rhPSMA-10.1 safe for humans?

177Lu rhPSMA-10.1 has been used in a patient with prostate cancer, showing a positive tumor response, but specific safety data for humans is limited. Preclinical studies suggest it has favorable properties, such as lower kidney uptake and faster blood clearance, which may indicate a safer profile compared to similar treatments. ^{4 6 7 8 9}

How is the drug 177Lu rhPSMA-10.1 different from other prostate cancer treatments?

177Lu rhPSMA-10.1 is a novel radiopharmaceutical that targets the prostate-specific membrane antigen (PSMA) and has been optimized for better pharmacological properties, potentially offering improved tumor targeting and reduced kidney uptake compared to other PSMA-targeted therapies. ^{3 4 5 7 8}

Research Team

Brian Chapin, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Men over 18 with high-risk, localized prostate cancer who haven't had previous treatments and are candidates for surgery. They must have a certain tumor size on MRI, no metastatic disease or positive lymph nodes (unless allowed by the doctor), good liver and kidney function, adequate bone marrow function, and agree to use condoms during sexual activity.

Inclusion Criteria

My prostate cancer is classified as high-risk or very high-risk.

My cancer is not small cell, neuroendocrine, or transitional cell carcinoma.

I can do light work but not heavy physical activities.

Exclusion Criteria

I am not currently taking Tenofovir.

I have no other cancers except for certain skin cancers or superficial bladder cancer in the last 2 years.

I have had a stem cell or organ transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 177Lu rhPSMA-10.1 alone or with ADT for 2 cycles

8-12 weeks

Surgery

Participants undergo radical prostatectomy with lymph node dissection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 177Lu rhPSMA-10.1
• Degarelix

Trial Overview The Nautilus Trial is testing the safety of a drug called 177Lu rhPSMA-10.1 alone (Arm A) and combined with hormone therapy Degarelix (Arm B) in men before they undergo surgery for high-risk prostate cancer. The trial will proceed to Phase 2 if Phase 1 shows that the dose is safe.

Participant Groups

Group I: LeadIn: Treatment with 177Lu rhPSMA-10.1 Experimental Treatment 2 Interventions

Participants will receive 177Lu rhPSMA-10.1 alone.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

AVEO Pharmaceuticals, Inc.

Industry Sponsor

Trials

46

Recruited

4,000+

Blue Earth Therapeutics

Collaborator

Trials

1

Recruited

40+

Findings from Research

In a study of 27 patients with metastatic castration-resistant prostate cancer undergoing radioligand therapy with [177Lu]PSMA-617, early changes in PSA levels after 4 weeks were found to be significant predictors of later treatment response and overall survival.

A decrease in PSA levels of at least 30% after 4 weeks was associated with better outcomes, while an increase of 25% or more indicated a higher risk of disease progression, suggesting that monitoring PSA changes early in treatment can guide patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early PSA Change after [177Lu]PSMA-617 Radioligand Therapy as a Predicator of Biochemical Response and Overall Survival. Kind, F., Fassbender, TF., Andrieux, G., et al.[2022]

177Lu-PSMA radioligand therapy (RLT) resulted in a greater decline in PSA levels (44%) compared to third-line treatments (22%) in patients with metastatic castration-resistant prostate cancer (mCRPC), indicating superior efficacy.

Patients receiving 177Lu-PSMA RLT experienced fewer adverse effects, with no treatment discontinuations due to side effects, while 10% to 23% of patients on third-line treatments had to stop due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review. von Eyben, FE., Roviello, G., Kiljunen, T., et al.[2019]

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 novel radiopharmaceutical 18F-rhPSMA-7.3 demonstrated high specificity (over 92%) for detecting pelvic lymph node metastases in newly diagnosed prostate cancer patients, meeting the prespecified specificity endpoint.

While the sensitivity for detecting these metastases was lower than expected (30% for the highest reader), it was higher in high-risk patients, and the agent was well tolerated with no serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Performance and Safety of Positron Emission Tomography with 18F-rhPSMA-7.3 in Patients with Newly Diagnosed Unfavourable Intermediate- to Very-high-risk Prostate Cancer: Results from a Phase 3, Prospective, Multicentre Study (LIGHTHOUSE). Surasi, DS., Eiber, M., Maurer, 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]

Among the four isomers of [18F, natGa]rhPSMA-7, [18F, natGa]rhPSMA-7.3 demonstrated the best pharmacokinetics, showing high tumor accumulation and low uptake in blood, liver, and kidneys, making it the preferred candidate for clinical studies.

The study utilized a novel intraindividual comparison method in LNCaP tumor-bearing mice to evaluate the differential uptake and excretion of the isomers, which was crucial in identifying [18F, natGa]rhPSMA-7.3 for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical comparison of four [18F, natGa]rhPSMA-7 isomers: influence of the stereoconfiguration on pharmacokinetics. Wurzer, A., Parzinger, M., Konrad, M., et al.[2020]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Early PSA Change after [177Lu]PSMA-617 Radioligand Therapy as a Predicator of Biochemical Response and Overall Survival. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review. [2019]

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

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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Diagnostic Performance and Safety of Positron Emission Tomography with 18F-rhPSMA-7.3 in Patients with Newly Diagnosed Unfavourable Intermediate- to Very-high-risk Prostate Cancer: Results from a Phase 3, Prospective, Multicentre Study (LIGHTHOUSE). [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]

8. Germany pubmed.ncbi.nlm.nih.gov

Preclinical comparison of four [18F, natGa]rhPSMA-7 isomers: influence of the stereoconfiguration on pharmacokinetics. [2020]

9. 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]