What side effects are associated with this type of intervention?

Radioligand therapy, such as [Lu-177]-PNT2002, used in treating metastatic castration-resistant prostate cancer (mCRPC), is generally well tolerated but can cause several side effects. Common adverse effects include myelosuppression (e.g., thrombocytopenia, lymphopenia, anemia, leukopenia), nephrotoxicity, and salivary gland toxicity (e.g., dry mouth, pain, swelling). Other treatments for prostate cancer, such as androgen receptor signaling inhibitors and taxane-based chemotherapy, can also lead to side effects like fatigue, nausea, and increased risk of infections due to bone marrow suppression. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer that involve radioligand therapy, which delivers targeted radiation to cancer cells. Notably, lutetium Lu 177 vipivotide tetraxetan has been approved for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with androgen-receptor pathway inhibitors and taxane-based chemotherapy. This approval was based on the VISION trial, which demonstrated significant improvements in progression-free survival and overall survival. Additionally, radium-223 (Ra-223) is another radiopharmaceutical approved for mCRPC, particularly for patients with symptomatic bone metastases and no known visceral metastatic disease.

What other types of research exist?

Promising alternatives to [Lu-177]-PNT2002 for prostate cancer treatment include: 1) [225Ac]-PSMA617, which uses targeted alpha therapy and has shown clinical potential in prostate cancer. 2) Radium-223, an alpha-emitting radiopharmaceutical approved for castration-resistant prostate cancer with bone metastases, demonstrating improved overall survival and reduced skeletal-related events. 3) Combination therapies involving [177Lu]-Dotatate, which have shown efficacy in neuroendocrine tumors and may be applicable to prostate cancer. These alternatives offer targeted radiation and have demonstrated promising results in clinical settings.

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Radioisotope Therapy

Lu-177 PSMA Therapy for Prostate Cancer (SPLASH Trial)

Phase 3

Waitlist Available

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

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Progression on previous treatment with one ARAT (abiraterone or enzalutamide or darolutamide or apalutamide) in either the CSPC or CRPC setting

Ineligible or averse to chemotherapeutic treatment options.

Must not have

A superscan on bone scan defined as a bone scan that demonstrates markedly increased skeletal radioisotope uptake relative to soft tissues in association with absent or faint genitourinary tract activity

Patients who progressed on 2 or more lines of ARATs

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a radioactive treatment in patients with advanced prostate cancer that hasn't responded to other treatments. The treatment targets and kills cancer cells using radiation and has shown promising outcomes, including reduced disease progression and improved overall survival.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

[Lu-177]-PNT2002 may cause nausea, fatigue, dry mouth, reduced blood cell counts leading to increased infection risk or bleeding problems, kidney issues due to radiation exposure, and potential allergic reactions to its components.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer progressed after treatment with a specific hormone therapy.

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I cannot or do not want to undergo chemotherapy.

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My PSMA-PET scan results are positive.

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I am fully active or can carry out light work.

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My prostate cancer is getting worse despite treatment.

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My cancer has grown by 20% or I have new cancer spots since starting treatment.

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My kidney function is within the required range.

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I will use effective birth control during the study and for 6 months after.

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I am a man aged 18 or older.

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I cannot or do not want to undergo chemotherapy.

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My testosterone levels are very low.

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My prostate cancer has been confirmed by a lab test.

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My bone scan shows two or more new lesions indicating my bone disease is progressing.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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My condition worsened after two or more ARAT treatments.

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I am experiencing symptoms or have been diagnosed with potential spinal cord compression.

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I have cancer, but it's not low-grade bladder cancer or non-melanoma skin cancer.

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I have taken PARP inhibitors for prostate cancer.

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I have had seizures and am planned to receive enzalutamide.

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I have previously received PSMA-targeted radioligand therapy.

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I have liver metastases larger than 1 cm.

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I have had treatment with radioactive drugs.

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I have not had prostate cancer treatment in the last 28 days, except for some specific initial treatments.

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I am not allergic to specific cancer imaging agents or their components.

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My prostate cancer has specific cell types but no small cell components.

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My cancer has spread to my brain.

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I have had immunotherapy before, but not sipuleucel-T.

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I haven't had a heart attack, blood clot, unstable heart pain recently, and my heart pumps well.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Radiographic Progression Free Survival (rPFS)

Secondary study objectives

Biochemical Progression-Free Survival (bPFS)

Duration of response

Objective Response Rate (ORR)

+2 more

Other study objectives

Safety and Tolerability (AEs)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: [Lu-177]-PNT2002 (Arm A)Experimental Treatment1 Intervention

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

Group II: Control Arm (Arm B)Active Control2 Interventions

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

0 / 28Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Radioligand therapy, such as [Lu-177]-PNT2002, targets prostate-specific membrane antigen (PSMA) on cancer cells, delivering localized radiation to destroy them while sparing surrounding healthy tissue. This targeted approach is crucial for prostate cancer patients as it potentially reduces side effects compared to traditional therapies. Other common treatments include androgen deprivation therapy (ADT), which reduces androgen levels to slow cancer growth, and chemotherapy, which uses drugs to kill rapidly dividing cells. Understanding these mechanisms helps in choosing the most effective and personalized treatment plan.

Biomarkers to personalize treatment with 177Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer - a state of the art review.Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies.