Lu-177 PSMA Therapy for Prostate Cancer

(SPLASH Trial)

Not currently recruiting at 59 trial locations

Overseen By Chantal R Trieu

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company

Must be taking: ARAT therapy

Must not be taking: Cytotoxic chemotherapy, Radionuclides

Disqualifiers: Sarcomatoid cancer, Liver metastases, CNS metastases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Lu-177-PNT2002 to evaluate its effectiveness and safety for individuals with prostate cancer that has spread and does not respond to common hormone treatments. Participants will receive either the experimental Lu-177-PNT2002 or standard hormone treatments such as abiraterone (Zytiga or Yonsa) or enzalutamide (Xtandi). This study suits men with advanced prostate cancer who have not succeeded with certain hormone therapies and are unable or unwilling to undergo chemotherapy. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients must not have had certain treatments like chemotherapy or investigational agents recently. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that [Lu-177]-PNT2002 is generally well-tolerated by patients. In earlier studies, no deaths were linked to the treatment, and only a few patients experienced serious side effects. This treatment specifically targets prostate cancer cells to help destroy them.

Overall, the safety profile appears promising, indicating it seems reasonably safe based on past tests. This information is important for anyone considering joining a trial with this treatment. ^{1 2 3 4 5}

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

[Lu-177]-PNT2002 is unique because it uses a targeted approach to treat prostate cancer. Unlike traditional treatments such as hormone therapies and chemotherapy, which affect the whole body, this therapy specifically targets cancer cells expressing the PSMA protein. This targeted delivery is achieved using a radioactive particle, Lu-177, which delivers radiation directly to the cancer cells, potentially reducing damage to healthy tissue. Researchers are excited about this treatment because it offers a more precise attack on cancer cells, which could lead to fewer side effects and improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that [Lu-177]-PNT2002, which participants in this trial may receive, holds promise for treating prostate cancer. In earlier studies, 36% of patients experienced a significant drop in prostate-specific antigen (PSA) levels, a key marker for tracking prostate cancer progress. This treatment has also been linked to longer periods without cancer progression. Additionally, [Lu-177]-PNT2002 is generally safe and well-tolerated by patients. These findings suggest that [Lu-177]-PNT2002 could be an effective option for those with advanced prostate cancer that hasn't responded to other treatments. Meanwhile, the control arm of this trial will involve treatment with either Abiraterone or Enzalutamide, which are standard therapies for prostate cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Jessica Jensen

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread, despite previous treatments like abiraterone or enzalutamide. They should not want chemotherapy, have a low risk of AIDS (if HIV-positive), show signs of worsening cancer, and have proper organ function. Contraception is required for those with partners at risk of pregnancy.

Inclusion Criteria

Bone marrow reserve: i. White blood cell (WBC) count ≥2.5 × 10^9/L OR absolute neutrophil count (ANC) ≥1.5 × 10^9/L

I am HIV positive but at low risk for AIDS.

Signed informed consent

Exclusion Criteria

My bone scan shows much more activity in bones than in soft tissues, with little to no activity in the urinary tract.

Concurrent illness that may jeopardize the patient's ability to undergo study procedures

My condition worsened after two or more ARAT treatments.

Timeline for a Trial Participant

Dosimetry

Safety and dosimetry lead-in with 25 patients to assess initial safety and dosimetry of the treatment

8 weeks

Randomized Treatment

Randomized treatment phase where patients receive either [Lu-177]-PNT2002 or control treatment (abiraterone or enzalutamide)

32 weeks

4 cycles every 8 weeks for [Lu-177]-PNT2002

Long-term Follow-up

Participants are monitored for safety and effectiveness after treatment for at least 5 years

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone
• Enzalutamide
• [Lu-177]-PNT2002

Trial Overview The trial tests [Lu-177]-PNT2002 effectiveness in men whose prostate cancer worsened after second-line hormonal therapies. Participants will either receive this new treatment or continue with standard care options like abiraterone or enzalutamide as decided by the study team.

How Is the Trial Designed?

Group I: [Lu-177]-PNT2002 (Arm A) Experimental Treatment 1 Intervention

\[Lu-177\]-PNT2002 (6.8 GBq (±10%) every 8 weeks for 4 cycles).

Group II: Control Arm (Arm B) Active Control 2 Interventions

Abiraterone (1000 mg orally qd with: 5 mg bid prednisone or 0.5 mg qd dexamethasone) or enzalutamide (160 mg orally qd).

Who Is Running the Clinical Trial?

POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company

Lead Sponsor

Trials

5

Recruited

670+

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

POINT Biopharma

Lead Sponsor

Trials

6

Recruited

720+

Published Research Related to This Trial

PSMA-targeted imaging and therapy have significantly improved the management of prostate cancer, particularly in advanced stages like metastasized castration-resistant prostate cancer.

Lutetium-177-conjugated PSMA-617 or PSMA-I&T (Lu-PSMA) has shown promising results in both multicenter retrospective and monocenter prospective trials, indicating its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Cancer Theranostics: PSMA Targeted Therapy. Seifert, R., Alberts, IL., Afshar-Oromieh, A., et al.[2021]

The LUNAR trial is investigating the efficacy of 177 Lu-PNT2002, a radiolabelled small molecule targeting prostate-specific membrane antigen (PSMA), in combination with stereotactic body radiotherapy (SBRT) for men with oligorecurrent metastatic hormone-sensitive prostate cancer, with 100 patients expected to be enrolled.

This Phase 2 trial aims to determine if adding 177 Lu-PNT2002 to SBRT can improve progression-free survival and other outcomes compared to SBRT alone, potentially offering a new treatment strategy for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LUNAR: a randomized Phase 2 study of 177 Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (clinical trial protocol). Ma, TM., Czernin, J., Felix, C., 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]

Prostate-specific membrane antigen (PSMA) is a key target for imaging and treating prostate cancer, with new small molecule peptides enabling high-quality PET imaging and targeted radionuclide therapy.

Early clinical studies of Lutetium 177 (Lu) PSMA therapy show promising safety and efficacy, with many men with metastatic prostate cancer responding positively even after failing other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. Emmett, L., Willowson, K., Violet, J., et al.[2022]

A case study demonstrated that 225 Ac-PSMA-617 therapy led to remission of clinical symptoms and imaging lesions in a patient with metastatic castration-resistant prostate cancer after 4 treatment cycles.

The patient experienced no observable adverse effects, suggesting that 225 Ac-PSMA-617 may be a safe and effective alternative for those who do not respond to 177 Lu-PSMA therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Multiple Bone Metastases of Castration-Resistant Prostate Cancer With 225 Ac-PSMA-617. Yang, H., Zhang, Y., Su, D., et al.[2023]

In a study of 84 Asian patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Lutetium-177 PSMA radioligand therapy, the median overall survival was 12.2 months and the median PSA progression-free survival was 5.2 months, indicating promising efficacy.

A significant 51.8% of patients experienced a PSA decline of 50% or more, which was linked to longer overall survival and PSA progression-free survival, while the treatment showed a manageable safety profile with grade 3 hematotoxicity occurring in 13 out of 78 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and prognostic predictors of Lu-177 PSMA radioligand therapy in metastatic castration-resistant prostate cancer (Asian Population Study). Chua, WM., Lam, WW., Tong, AK., et al.[2023]

Alterations in aggressive-variant prostate cancer (AVPC) genes found in circulating tumor DNA (ctDNA) were linked to shorter prostate-specific antigen (PSA) progression-free survival and overall survival in men treated with Lu-PSMA, indicating that these genetic changes could help predict treatment outcomes.

The study analyzed ctDNA from 32 men undergoing Lu-PSMA therapy combined with idronoxil, suggesting that identifying specific molecular biomarkers may refine patient selection and improve therapeutic strategies for metastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Tumour DNA Biomarkers Associated with Outcomes in Metastatic Prostate Cancer Treated with Lutetium-177-PSMA-617. Crumbaker, M., Goldstein, LD., Murray, DH., et al.[2023]

In a study involving patients with metastatic castration-resistant prostate cancer who had previously failed other treatments, (177)Lu-PSMA-I&T therapy demonstrated a favorable safety profile, with no severe toxicities observed at higher doses, and manageable side effects like dry mouth and anemia.

The therapy showed promising efficacy, with 56% of patients achieving a prostate-specific antigen decrease of 30% or more, and 74% of patients experiencing stable or improved performance status, indicating potential benefits in managing this advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Radioligand Therapy with (177)Lu Labeled Prostate Specific Membrane Antigen Ligand for Imaging and Therapy in Patients with Metastatic Castration Resistant Prostate Cancer. Heck, MM., Retz, M., D'Alessandria, C., et al.[2019]

Citations

1. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-prostate-cancer/154850-esmo-2024-efficacy-of-177lu-pnt2002-in-psma-positive-mcrpc-following-progression-on-an-androgen-receptor-pathway-inhibitor-splash.html

ESMO 2024: Efficacy of 177Lu-PNT2002 in PSMA-Positive ... A PSA50 response was observed in 36% and 15% of patients, respectively. Biochemical progression-free survival similarly favored 177Lu-PNT2002 ( ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39839782/

Initial clinical experience with [177Lu]Lu-PNT2002 ... Conclusion: [177Lu]Lu-PNT2002, administered at 6.8 GBq/cycle for 4 cycles, demonstrated a favorable dosimetry and safety profile, as well as ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04647526

Study Evaluating mCRPC Treatment Using PSMA [Lu-177] ... The purpose of this study is to evaluate the efficacy and safety of [Lu-177]-PNT2002 in patients with metastatic castration-resistant prostate cancer who have ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1483953/full

Initial clinical experience with [ 177 Lu]Lu-PNT2002 ... Conclusion: [177Lu]Lu-PNT2002, administered at 6.8 GBq/cycle for 4 cycles, demonstrated a favorable dosimetry and safety profile, as well as ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.TPS5087

Study evaluating metastatic castrate resistant prostate ... This trial seeks to prospectively evaluate the efficacy of 177 Lu-PNT2002 for men with progressive mCRPC after androgen receptor axis-targeted (ARAT) therapy.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04647526

Study Evaluating mCRPC Treatment Using PSMA [Lu-177 ... The purpose of this study is to evaluate the efficacy and safety of [Lu-177]-PNT2002 in patients with metastatic castration-resistant prostate cancer.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2107322

Lutetium-177–PSMA-617 for Metastatic Castration ... Here, we report the results of VISION, a phase 3 trial investigating the efficacy and safety of 177Lu-PSMA-617 plus protocol-permitted standard care in a ...