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

(PSMAddition Trial)

Recruiting at 242 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

1144 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if adding a radioactive drug to standard hormone treatments can better treat men with advanced prostate cancer. The drug targets and kills cancer cells with radiation, while standard treatments block hormones that help cancer grow.

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.

What data supports the effectiveness of the drug 177Lu-PSMA-617 for prostate cancer?

The drug 177Lu-PSMA-617 has been shown to be effective in treating prostate cancer, particularly in patients with advanced forms of the disease. It works by delivering targeted radiation to cancer cells, sparing healthy tissue, and has been approved by the FDA for use in certain prostate cancer patients. Clinical trials have demonstrated its ability to reduce prostate-specific antigen (PSA) levels, which is a marker of prostate cancer activity, and improve survival rates. ^{1 2 3 4 5}

Is 177Lu-PSMA-617 safe for humans?

177Lu-PSMA-617, also known as Pluvicto, has been shown to have a good safety profile in clinical trials for prostate cancer, with common side effects including tiredness, nausea, dry mouth, low blood cell counts, and diarrhea. ^{1 4 5 6 7}

What makes the drug 177Lu-PSMA-617 unique for prostate cancer treatment?

177Lu-PSMA-617 is unique because it is a radioligand therapy that specifically targets prostate-specific membrane antigen (PSMA) on prostate cancer cells, delivering radiation directly to the tumor while sparing healthy tissue. It is particularly used for patients with metastatic castration-resistant prostate cancer who have not responded to other treatments. ^{1 3 4 8 9}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

[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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. [2023]

2. England 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

5. England 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). [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617: A Vision of the Future. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

Factors affecting overall survival and progression-free survival in patients with metastatic castration resistant prostate cancer received 177Lu PSMA I&T therapy. [2021]

8. Germany 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. [2023]