Lu-PSMA-617 for Liver Cancer

Overseen By Melissa Lumish, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Melissa Lumish

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Brain metastases, Uncontrolled illness, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of a drug called Lu-PSMA-617 for individuals with liver cancer that exhibits a specific marker known as PSMA. The researchers aim to determine the drug's effectiveness and potential side effects. Eligible participants should have liver cancer that has spread and not responded to previous treatments, with a PSMA-positive lesion. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents or have received investigational therapy recently. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that Lu-PSMA-617 is likely to be safe for humans?

Research has shown that Lu-PSMA-617 is generally well-tolerated. This treatment uses a special type of radiation to target cancer cells and has proven to be safe. In a large study, fewer patients experienced severe side effects with Lu-PSMA-617 compared to another treatment. Most side effects were mild and manageable. This treatment is already approved for other types of cancer, demonstrating its safety for people. The current study is in the middle phase of testing and aims to further confirm its safety for liver cancer patients. ^{1 2 3 4 5}

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

Unlike the standard treatments for liver cancer, which often include surgery, chemotherapy, or targeted therapies like sorafenib, Lu-PSMA-617 introduces a novel approach by using a radiopharmaceutical. This treatment works by delivering a radioactive particle directly to cancer cells via a molecule that specifically targets the prostate-specific membrane antigen (PSMA), which is also found in some liver cancers. This targeted delivery allows for precise radiation to cancer cells while sparing healthy tissue, potentially reducing side effects and enhancing effectiveness. Researchers are excited about Lu-PSMA-617 because it represents a new mechanism of action that could improve outcomes for patients who have limited options.

What evidence suggests that Lu-PSMA-617 might be an effective treatment for liver cancer?

Research has shown that Lu-PSMA-617 can effectively slow prostate cancer progression and reduce the risk of death. It can decrease cancer growth by 60% and lower the risk of death by 38% when combined with standard treatments. However, patients with cancer that has spread to the liver tend to have worse outcomes with this treatment. While Lu-PSMA-617 is promising, it may not work as well for those with liver involvement. The treatment targets a protein called PSMA on cancer cells and delivers radiation directly to them. Participants in this trial will receive Lu-PSMA-617 to evaluate its effectiveness specifically for liver cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Melissa Lumish, MD

Principal Investigator

Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with liver cancer that tests positive for a protein called PSMA. Specific details about who can join or reasons why someone might not be eligible are not provided in the information given.

Inclusion Criteria

I have had one treatment for my liver cancer that cannot be surgically removed.

My blood counts and kidney function are within normal ranges.

Participants must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

I have had Y90 treatment for liver cancer.

I had major surgery less than 3 months ago and haven't fully recovered.

I do not have untreated brain metastases or carcinomatous meningitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 177Lu-PSMA-617 intravenously every 6 weeks

6 weeks

1 visit (in-person) every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lu-PSMA-617

Trial Overview The study is examining the effects of a drug named 177Lu-PSMA-617 on patients with PSMA-positive liver cancer to determine its safety and effectiveness.

How Is the Trial Designed?

Group I: Lu-PSMA-617 Experimental Treatment 1 Intervention

Participants will receive 177Lu-PSMA-617 7.4 GBq (200 mCi) once every 6 weeks. 177Lu-PSMA-617 is a radiopharmaceutical which will be administered intravenously (IV).

Who Is Running the Clinical Trial?

Melissa Lumish

Lead Sponsor

Trials

1

Recruited

10+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Published Research Related to This Trial

In a study involving 64 patients with metastatic castration-resistant prostate cancer, 177Lu-PSMA-617 was found to be safe and well-tolerated, with manageable side effects such as dry mouth, fatigue, and nausea occurring in a significant number of patients.

The treatment did not lead to serious adverse events directly related to the drug, and there were no significant changes in vital signs or kidney function, suggesting a favorable safety profile for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312). Calais, J., Czernin, J., Thin, P., et al.[2023]

In a study of seven patients with progressive prostate cancer, (177)Lu-PSMA-617 therapy was found to be safe, with the highest radiation doses absorbed by the parotid glands (1.17 mGy/MBq) and kidneys (0.88 mGy/MBq), while the bone marrow received a significantly lower dose (0.03 mGy/MBq).

The findings suggest that the parotid glands are the dose-limiting organs in this therapy, indicating that individual patient dosimetry is essential due to substantial variations in radiation absorption among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer. Kabasakal, L., AbuQbeitah, M., Aygün, A., et al.[2021]

In a study of 24 patients with hormone and/or chemorefractory metastatic prostate cancer, 79.1% experienced a decline in PSA levels after the first cycle of Lu-PSMA therapy, indicating a strong efficacy of this treatment.

Lu-PSMA therapy demonstrated a low toxicity profile, with only two cases of grade 3 anemia reported and no significant hemato- or nephrotoxicity, confirming its safety for patients with advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Ahmadzadehfar, H., Eppard, E., Kürpig, S., et al.[2022]

[177Lu]Lu-PSMA-617 is effective in targeting prostate cancer, but some patients do not respond well; ongoing research is exploring combination therapies to improve outcomes for both treatment-naïve and resistant patients.

Combining [177Lu]Lu-PSMA-617 with other treatments, such as alpha radiation emitters and immune checkpoint inhibitors, shows promise in enhancing therapeutic responses, particularly for patients who have developed resistance to initial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. Arbuznikova, D., Eder, M., Grosu, AL., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11939846/

Efficacy of 177Lu-PSMA-617 Therapy in mCRPC Patients ... Clinical studies have shown that Lu-PSMA-617 reduces progression by 60% and overall mortality by 38% when combined with standard therapy [13,16, ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/65/12/1932

Outcomes for Patients with Metastatic Castration-Resistant ... Our data suggest that the presence of liver metastasis predicts poorer outcomes in patients receiving LuPSMA treatment.

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

Lutetium-177–PSMA-617 for Metastatic Castration ... Lu-PSMA-617 plus standard care significantly prolonged, as compared with standard care, both imaging-based progression-free survival (median, 8.7 vs. 3.4 months ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.175

Outcomes for patients with mCRPC and liver metastasis ... Our data suggest that the presence of liver metastases predict poorer outcomes in patients receiving Lutetium-177–PSMA-617 treatment.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06852820

NCT06852820 | 68Ga-PSMA-11 PET-directed Radioligand ... The purpose of this study is to look at the effects (good and bad) of a drug called 177Lu-PSMA-617 (also known as the study drug) when given ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-06673

A Radioactive Drug (177Lu–PSMA-617) for the Treatment ... This phase I trial studies the feasibility, safety, and side effects of a radioactive drug called 177Lu–PSMA-617, and evaluates its effect in treating patients ...

7. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251339

Comparative Safety and Efficacy of 177Lu-PSMA-617 and ... In this first comparative analysis of 177 Lu-PSMA-617 and 177 Lu-PSMA-I&T RLT in Taiwanese mCRPC patients, both agents demonstrated similar safety and efficacy.

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00852-X/fulltext

Final overall survival and safety analyses of the phase III ... Lu-PSMA-617 had a favourable safety profile, with a lower incidence of grade 3-5 adverse events (AEs) compared with ARPI change, and no new ...