Lutetium PSMA + SBRT for Prostate Cancer

(LUNAR Trial)

Overseen By Christie Palodichuk

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Androgen deprivation therapy

Disqualifiers: Neuroendocrine carcinoma, Castrate-resistant, 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: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for prostate cancer that has returned after previous treatments. Researchers aim to determine if a radioactive drug, 177-Lutetium-PSMA (also known as Lutetium Lu-177 PNT2002), used before a precise form of radiation therapy (SBRT), can better control cancer with fewer side effects. The trial includes two groups: one receiving only the radiation and the other receiving both the drug and radiation. Men with prostate cancer that has returned and is found in 1-5 spots outside the prostate, who are not currently experiencing symptoms, might be suitable for this study. As a Phase 2 trial, this study measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to important research.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on androgen deprivation therapy or any systemic therapy for another cancer, you may not be eligible to participate.

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

Research has shown that 177-Lutetium-PSMA (Lu-177 PNT2002) is generally safe for people. In earlier studies, this treatment did not cause any drug-related deaths. Only a few patients experienced serious side effects, and most tolerated the treatment well.

This drug uses radiation to specifically target cancer cells, potentially protecting normal cells from damage. This targeted approach shows promise for treating prostate cancer, especially when combined with other treatments like stereotactic body radiotherapy (SBRT).

In summary, evidence suggests that 177-Lutetium-PSMA is well-tolerated and safe for treating prostate cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Lutetium Lu-177 PNT2002 combined with stereotactic body radiotherapy (SBRT) because it introduces a novel approach to treating prostate cancer. Unlike traditional hormone therapies or chemotherapy, this treatment uses a radioactive compound, Lutetium-177, which specifically targets prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation directly to the tumor. This targeted action could potentially minimize damage to surrounding healthy tissue. Additionally, combining it with SBRT, which precisely focuses high doses of radiation on tumors, aims to enhance treatment effectiveness while reducing side effects. This innovative combination offers a promising alternative to current prostate cancer therapies.

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

Research has shown that 177-Lutetium-PSMA, similar to Lutetium Lu-177 PNT2002, effectively targets prostate cancer cells. In studies, it significantly lowered prostate-specific antigen (PSA) levels, a key marker for monitoring prostate cancer. Specifically, 36% of patients experienced a 50% reduction in PSA levels. It also extended the time patients lived without cancer progression. Overall, patients treated with this radioactive drug reported better outcomes, including improved quality of life. In this trial, some participants will receive Lutetium Lu-177 PNT2002 alongside Stereotactic Body Radiation Therapy (SBRT), while others will receive SBRT alone. These findings support its potential effectiveness in treating recurring prostate cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Amar Kishan

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Men over 18 with prostate adenocarcinoma that's come back in 1-5 spots after treatment can join. They need good blood counts, liver and kidney function, and must be feeling well enough to do daily activities. No recent hormone therapy for cancer or other solid tumors being treated, no lying flat issues, or allergies to the radioactive drug used.

Inclusion Criteria

Hemoglobin >= 9 g/dL

White blood cell count >= 2.5 × 10^9/L

Partner and patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 3 months after last study drug administration

Exclusion Criteria

My prostate cancer is of the neuroendocrine or small cell type.

I have received hormone therapy for cancer within the last 6 months.

My kidney function is below normal levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 177Lu-PNT2002 intravenously on days -112 and -56

8 weeks

2 visits (in-person)

Stereotactic Body Radiotherapy (SBRT)

Participants undergo SBRT to all lesions for 1, 3, or 5 treatment doses over 10-20 days

2-3 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

Visits at 1, 3, 6, 9, and 12 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium Lu-177 PNT2002
• Stereotactic Body Radiation Therapy

Trial Overview The LUNAR study is testing if a radioactive drug called 177-Lutetium-PSMA given before precise radiation therapy (SBRT) helps control recurrent prostate cancer better. The idea is that the drug targets tumor cells without hurting normal ones and makes SBRT more effective.

How Is the Trial Designed?

Group I: Arm 2 (177Lu-PNT2002, SBRT) Experimental Treatment 3 Interventions

Patients receive 177Lu-PNT2002 IV over 1-10 minutes on days -112 and -56 in the absence of disease progression or unacceptable toxicity. Beginning on day 1, patients then undergo SBRT to all lesions for 1, 3, or 5 treatment doses (fractions) over the span of 10-20 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm 1 (SBRT) Active Control 2 Interventions

Beginning on day 1, patients undergo SBRT to all lesions for 1, 3, or 5 treatment doses (fractions) over the span of 10-20 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

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

Industry Sponsor

Trials

5

Recruited

670+

Eli Lilly and Company

Industry 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

Industry Sponsor

Trials

6

Recruited

720+

Published Research Related to This Trial

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]

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 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]

Treatment with lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA) significantly reduces prostate-specific antigen (PSA) levels in patients with advanced metastatic prostate cancer, especially after the first treatment cycle.

The therapy shows a beneficial effect on reducing lymph node metastasis, while also indicating potential negative impacts on visceral metastasis, highlighting its efficacy in managing certain aspects of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. Rathore, R., Rangrej, SB., Kieme, I., et al.[2023]

The ENZA-p trial is investigating the safety and efficacy of combining lutetium-177 (177 Lu)-PSMA-617 with enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC), aiming to improve prostate-specific antigen (PSA) progression-free survival (PFS) in high-risk patients.

This phase 2 trial will enroll 160 participants and assess various outcomes, including overall survival and quality of life, while also identifying potential biomarkers to personalize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). Emmett, L., Subramaniam, S., Joshua, AM., et al.[2022]

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]

Citations

1. bjui-journals.onlinelibrary.wiley.com bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.15988

LUNAR: a randomized Phase 2 study of 177 Lutetium-PSMA ... Compared to 177Lu-PSMA-617 in the VISION trial [27], 177Lu-PNT2002 has potential advantages including reduced dosage (6.8 GBq vs 7.4 GBq), ...

2. 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 ( ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11745944/

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

4. lantheusholdings.gcs-web.com lantheusholdings.gcs-web.com/news-releases/news-release-details/lantheus-presents-results-primary-analysis-phase-3-pivotal

Lantheus Presents Results from the Primary Analysis of Phase ... In the SPLASH study, 177Lu-PNT2002 patients demonstrated significantly improved ORR, PSA50 reduction, time to reduction of HRQoL, and time to ...

5. mayoclinic.org mayoclinic.org/medical-professionals/cancer/news/lutetium-177-shows-significant-rpfs-benefit-for-metastatic-prostate-cancer/mac-20561488

Lutetium-177 shows significant rPFS benefit for metastatic ... Patients treated with 177Lu -PSMA-617 had a more effective reduction in prostate-specific antigen and an improved quality of life.

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

Initial clinical experience with [177Lu]Lu-PNT2002 ... [177Lu]Lu-PNT2002 was associated with no treatment-related deaths, few treatment-related grade ≥3 treatment-emergent adverse events (TEAEs), and ...