177Lu-PSMA-617 + Standard Therapy for Prostate Cancer

(PSMAddition Trial)

Not currently recruiting at 282 trial locations

Overseen By Nabil Adra

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Androgen therapy

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: CNS metastases, Cardiac disease, 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: 7

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness and safety of a new treatment, 177Lu-PSMA-617 (also known as Pluvicto), combined with standard prostate cancer treatments, compared to standard treatments alone. It focuses on men with metastatic prostate cancer. The trial tests whether adding 177Lu-PSMA-617 can improve outcomes for these patients. Men diagnosed with prostate cancer that has spread and who meet certain health standards may qualify for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like first-generation anti-androgens must be stopped before starting the study therapy, and you cannot be on other investigational drugs or certain prostate cancer therapies.

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

Research has shown that 177Lu-PSMA-617, when combined with standard prostate cancer treatments, is generally well-tolerated. One study found that most patients managed side effects, which commonly included tiredness, dry mouth, and nausea. Some patients experienced low blood counts, which help fight infections, but this was not severe for most.

Another study tracked patients over time and confirmed that the treatment remained safe, with no unexpected problems appearing later. While a few patients experienced more serious side effects, these were rare.

Overall, evidence suggests that 177Lu-PSMA-617 is safe for many with prostate cancer. It is important to discuss any concerns with a healthcare provider to understand how it might affect an individual personally. ^{1 2 3 4 5}

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

Unlike the standard of care for prostate cancer, which typically includes androgen deprivation therapy (ADT) and androgen receptor-directed therapy (ARDT), 177Lu-PSMA-617 offers a novel approach by targeting prostate-specific membrane antigen (PSMA). This treatment uses a radioactive particle, Lutetium-177, that binds specifically to PSMA, which is abundant on prostate cancer cells, allowing for precise delivery of radiation directly to the cancer cells while sparing most healthy tissues. Researchers are excited about 177Lu-PSMA-617 because it combines targeted therapy with radiotherapy, potentially enhancing effectiveness and reducing side effects compared to conventional treatments.

What evidence suggests that 177Lu-PSMA-617 might be an effective treatment for prostate cancer?

Research has shown that adding 177Lu-PSMA-617 to standard prostate cancer treatments can greatly improve patient outcomes. One study found that it increased the time patients lived without their cancer worsening from about 3.4 months to 8.7 months. This treatment targets a protein called PSMA on prostate cancer cells and delivers radiation directly to them, helping to kill the cancer cells. Another study demonstrated that patients receiving this treatment lived longer on average. Overall, these findings suggest that 177Lu-PSMA-617 is a promising option for treating prostate cancer. Participants in this trial will either receive 177Lu-PSMA-617 in addition to the standard of care (ARDT + ADT) or the standard of care alone. ^{1 2 5 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adult men with metastatic hormone-sensitive prostate cancer, who have visible bone or soft tissue/visceral lesions and are either treatment-naive or minimally treated. They must be over 18 years old, have a life expectancy of more than 9 months, good organ function, no severe concurrent conditions, and not be on other clinical trials.

Inclusion Criteria

Patients must have a life expectancy >9 months as determined by the study investigator

Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader

Patients must have adequate organ function: Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dL Hepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3 x ULN is permitted Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation Albumin ≥2.5 g/dL Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial

Exclusion Criteria

I haven't had specific radiation treatments or PSMA-targeted therapy in the last 6 months.

I am not currently on any strong cancer treatments like chemotherapy.

I agree to use a condom during the study and for 14 weeks after, and not to donate sperm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Standard of Care with or without 177Lu-PSMA-617, administered every 6 weeks for 6 cycles

36 weeks

6 visits (in-person)

Cross-over

Participants in the control arm may cross-over to receive 177Lu-PSMA-617 after radiographic progression

Variable

Post-Treatment Follow-Up

Participants are monitored for safety and efficacy for 12 months after treatment discontinuation

12 months

Regular follow-up visits

Survival Follow-Up

Participant's survival status is collected every 90 days via phone calls

Until final OS analysis

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-PSMA-617
• 68Ga-PSMA-11
• ADT
• ARDT

Trial Overview

The trial is testing the effectiveness and safety of adding a drug called 177Lu-PSMA-617 to the standard prostate cancer treatments (Androgen Receptor Directed Therapy + Androgen Deprivation Therapy) compared to the standard treatments alone in about 1126 patients.

How Is the Trial Designed?

Group I: 177Lu-PSMA-617 Experimental Treatment 4 Interventions

Participant will receive 7.4 GBq (+/- 10%) 177Lu-PSMA-617, once every 6 weeks (+/- 1 week) for a planned 6 cycles, in addition to the Standard of Care (SOC); ARDT +ADT is considered as SOC and treatment will be administered per the physician's order

Group II: Standard of Care Active Control 3 Interventions

For participants randomized to Standard of Care arm, ARDT +ADT is considered as SOC and treatment will be administered per the physician's order

177Lu-PSMA-617 is already approved in United States, European Union for the following indications:

Approved in United States as Pluvicto for:

• Metastatic castration-resistant prostate cancer

Approved in European Union as Pluvicto for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Alliance Foundation Trials, LLC.

Collaborator

Trials

25

Recruited

27,200+

RTOG Foundation, Inc.

Collaborator

Trials

7

Recruited

1,500+

Published Research Related to This Trial

In a study involving 40 chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC), Lutetium-177 PSMA-617 showed a best prostate-specific antigen response rate of 60%, compared to 40% for docetaxel, demonstrating its efficacy as a treatment option.

177Lu-PSMA-617 was associated with fewer severe adverse events and significantly improved quality of life compared to docetaxel, suggesting it may be a safer alternative that could be used earlier in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial. Satapathy, S., Mittal, BR., Sood, A., 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]

[177Lu]Lu-PSMA-617 (PluvictoTM) is an FDA-approved treatment for prostate cancer specifically for patients with PSMA-positive metastatic castration-resistant prostate cancer who have already undergone other therapies.

This treatment uses a targeted radioligand therapy that delivers radiation directly to tumor cells, effectively killing them while minimizing damage to healthy tissue, as shown in multiple clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Hennrich, U., Eder, M.[2022]

In a phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of 177Lu-PSMA-617 to standard care significantly improved both imaging-based progression-free survival (8.7 months vs. 3.4 months) and overall survival (15.3 months vs. 11.3 months).

While 177Lu-PSMA-617 was associated with a higher incidence of grade 3 or above adverse events (52.7% vs. 38.0%), it did not negatively impact the patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. Sartor, O., de Bono, J., Chi, KN., et al.[2023]

The UpFrontPSMA trial is evaluating the effectiveness and safety of combining lutetium-177 (177 Lu)-PSMA-617 with docetaxel in 140 men with newly diagnosed metastatic hormone-naïve prostate cancer, aiming to determine the proportion of patients achieving undetectable PSA levels after 12 months.

This study is significant as it compares the experimental treatment to standard docetaxel therapy while all patients receive continuous androgen deprivation therapy, potentially providing insights into improved treatment strategies for this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UpFrontPSMA: a randomized phase 2 study of sequential 177 Lu-PSMA-617 and docetaxel vs docetaxel in metastatic hormone-naïve prostate cancer (clinical trial protocol). Dhiantravan, N., Emmett, L., Joshua, AM., et al.[2021]

177Lu-PSMA-617 therapy has shown promising efficacy in treating metastatic prostate cancer, with a majority of patients experiencing a decline in prostate-specific antigen (PSA) levels, which is associated with longer survival rates.

The analysis of 17 studies indicated that while significant toxicities were infrequent, cytopenias were noted, and factors like performance status and tumor grade were important predictors of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer. Sun, M., Niaz, MO., Nelson, A., et al.[2020]

The VISION trial demonstrated that Lutetium-177[177Lu]Lu-PSMA-617 significantly improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy, marking a breakthrough in treatment options.

Both the VISION and TheraP trials showed that [177Lu]Lu-PSMA-617 has a favorable safety profile, with common side effects including fatigue and nausea, suggesting it could be beneficial even for patients who have undergone extensive prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617: A Vision of the Future. Chandran, E., Figg, WD., Madan, R.[2022]

In a phase 2 trial involving 30 men with metastatic castration-resistant prostate cancer, 57% achieved a significant PSA decline of 50% or more after treatment with Lutetium-177 [177Lu]-PSMA-617, indicating its efficacy in this patient population.

The treatment was associated with low toxicity, with the most common side effects being mild dry mouth and transient nausea, and it also led to clinically meaningful improvements in pain and quality of life for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Hofman, MS., Violet, J., Hicks, RJ., et al.[2021]

Citations

1.

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 ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40752988/

Outcomes for [ 177 Lu]Lu-PSMA-617 with and Without ...

Key findings and limitations: Among 256 patients, 106 (41.4%) received an ARPI with [177Lu]Lu-PSMA-617. Those receiving an ARPI had lower ...

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.97

Real world outcomes of 177 Lu-PSMA-617 ...

The cohort completed a median number of 4 cycles of 177Lu-PSMA-617; 35.7% completed six cycles. The overall cohort had a 12-month survival of ...

4.

jnm.snmjournals.org

jnm.snmjournals.org/content/66/supplement_1/251559

Overall survival of prostate cancer patients treated with Lu-177 ...

Median overall survival was found to be approximately 4 months higher than OS reported in VISION trial and equal to that in TheraP trial.

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1558767325000989

Safety and Efficacy of Lutetium-177 PSMA Therapy for ...

[177Lu]Lu-PSMA-617 is a radioactive drug that binds to PSMA and delivers radiation directly to prostate cancer cells. This can kill the cancer cells while ...

6.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS294

Long-term safety outcomes of 177Lu-PSMA-617 in patients ...

It is important to further characterize long-term safety outcomes in 177 Lu-PSMA-617–treated patients, with particular regard to potential treatment-related ...

7.

annalsofoncology.org

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

Final overall survival and safety analyses of the phase III ...

At the time of the final OS analysis, 299 deaths were reported in 142/234 participants (60.7%) in the 177Lu-PSMA-617 arm and 157/234 (67.1%) in ...