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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effects of a new treatment, 177Lu rhPSMA-10.1, for men with high-risk prostate cancer. The study will explore how this treatment works both alone and alongside hormone therapy before surgery. Men with localized prostate cancer planning surgery might be suitable candidates, especially if they have not received prior treatments. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research has shown that 177Lu rhPSMA-10.1 is generally well-tolerated. In earlier studies, this treatment produced promising results with manageable side effects. Patients received higher radiation doses to tumors than to healthy tissues, effectively targeting cancer cells and reducing harm to the rest of the body.

Degarelix, already approved by the FDA for treating prostate cancer, has a well-understood safety profile. However, some patients might experience side effects such as hot flashes or reactions at the injection site.

Overall, current evidence suggests both treatments are expected to be safe, but further studies will help confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about 177Lu rhPSMA-10.1 because it offers a novel approach to treating prostate cancer by targeting a specific molecule called PSMA, which is often found in high levels in prostate cancer cells. Unlike traditional treatments such as surgery, radiation, and hormone therapy, which can affect both cancerous and healthy tissues, 177Lu rhPSMA-10.1 delivers radiation directly to cancer cells, potentially reducing side effects. Additionally, when combined with hormone therapy like Degarelix, it could enhance the overall effectiveness by disrupting the cancer’s growth signals. This targeted strategy not only aims to improve treatment outcomes but also enhances the quality of life for patients by minimizing damage to healthy tissues.

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

Research has shown that 177Lu rhPSMA-10.1, a new treatment for prostate cancer, appears promising. Early studies demonstrated that it helped shrink tumors and was generally well tolerated by patients. This treatment targets cancer cells with radiation, killing them while mostly sparing healthy tissue. Some data indicated that tumors absorbed more radiation than healthy tissues, suggesting effectiveness with fewer side effects. Although more research is needed, these initial findings are a positive sign for its potential in treating prostate cancer. Participants in this trial will receive 177Lu rhPSMA-10.1 alone. ^{1 2 3 6 7}

Who Is on the Research Team?

Brian Chapin, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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

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

3. 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.

4. 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.

5. 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 ...

6. ejnmmipharmchem.springeropen.com ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-024-00246-2

Preclinical comparison of [ 177 Lu]Lu-rhPSMA-10.1 and [ 177 ... [ 177 Lu]Lu-rhPSMA-10.1 shows fast kidney clearance kinetics resulting in excellent tumor-to-organ ratios over a therapy relevant time course.

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

A novel synergistic drug combination of a mitogen ... The prostate-specific membrane antigen (PSMA)-targeted radiohybrid ligand [177Lu]Lu-rhPSMA-10.1 is a promising next-generation radiopharmaceutical therapy ...