177Lu-PSMA for Cancer

Overseen By Dana B Kaplin

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Investigational agents

Disqualifiers: Spinal cord compression, Pulmonary metastases, 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: Unknown

Duration: 24 months

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called 177Lu-PNT2002, a targeted radiotherapy, for individuals with advanced adenoid cystic carcinoma (ACC) that cannot be surgically removed. Researchers aim to determine if this treatment can safely target cancer cells using a special imaging technique. The study includes participants whose ACC has returned or spread and cannot be treated with surgery or radiation. Participants must have a specific imaging result showing that the cancer cells absorb a particular tracer better than the liver. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you need to wait at least 28 days or 5 half-lives after your last anti-cancer treatment before starting the study treatment.

Is there any evidence suggesting that 177Lu-PNT2002 is likely to be safe for humans?

Research has shown that 177Lu-PNT2002 was safe in earlier studies. In one study, patients received this treatment in cycles, and most tolerated it well. Some side effects occurred, but serious ones were rare. For instance, only a few experienced severe issues related to the treatment.

Additionally, one death was reported, but it was not linked to the treatment. While risks exist, current information generally considers the treatment safe. However, individual reactions may vary, so discussing any concerns with a doctor is crucial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for cancer?

Most treatments for prostate cancer, like chemotherapy and hormone therapy, focus on reducing or stopping cancer cell growth. But 177Lu-PNT2002 works differently by using a radioactive compound to specifically target and bind to prostate-specific membrane antigen (PSMA) on cancer cells. This targeted approach allows the radiation to directly hit the tumor cells while sparing most of the healthy tissue, potentially leading to fewer side effects. Researchers are excited because this precision in treatment could mean better outcomes and a higher quality of life for patients.

What evidence suggests that 177Lu-PNT2002 might be an effective treatment for adenoid cystic carcinoma?

Research has shown that 177Lu-PNT2002, a type of targeted radiotherapy, holds promise for treating certain cancers. In this trial, participants will receive 177Lu-PNT2002, and researchers will measure its effects using SPECT/CT dosimetry. Similar treatments, such as Lu-PSMA-617, have proven effective in helping patients live longer without cancer progression. In some studies, a small number of patients had their cancer become undetectable after treatment. This therapy is considered relatively safe, with a good response rate and low side effects. While most research has focused on prostate cancer, these findings suggest it might also benefit other PSMA-positive cancers. ^{3 6 7 8 9}

Who Is on the Research Team?

Ana Kiess, MD, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for people with recurrent or metastatic adenoid cystic carcinoma that's not suitable for surgery. Participants will be part of a study at Johns Hopkins, undergoing special imaging and possibly treatment with the drug 177Lu-PNT2002 if they move to Cohort 2 after initial assessments.

Inclusion Criteria

I can understand and am willing to sign the consent form.

My cancer, ACC, has been confirmed by a pathology review.

My ACC cancer has returned or spread and can't be removed by surgery or treated with radiotherapy.

Exclusion Criteria

Patient receiving any other investigational agents

Any medical comorbidities that might preclude safe participation in the study

Refusal to sign informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

SPECT CT Dosimetry

Absorbed dose in tumor and normal organs will be measured using SPECT/CT dosimetry in Cohort 1

1 day

Treatment

Participants undergo treatment with 177Lu-PNT2002, including bloodwork, physical exams, and imaging at study-specific time points

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-PNT2002

Trial Overview The trial is testing the use of a radioactive drug called 177Lu-PNT2002 in patients with specific cancer. Initially, participants undergo diagnostic imaging; if results are favorable, they may receive the actual treatment in Cohort 2.

How Is the Trial Designed?

Group I: SPECT CT Dosimetry Experimental Treatment 1 Intervention

Absorbed dose in tumor and normal organs will by measured using SPECT/CT dosimetry in Cohort 1.

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Adenoid Cystic Carcinoma Research Foundation

Collaborator

Trials

7

Recruited

160+

Progenics Pharmaceuticals, Inc.

Industry Sponsor

Trials

35

Recruited

4,400+

Published Research Related to This Trial

In a patient with metastatic castration-resistant prostate cancer (mCRPC), four cycles of radioligand therapy (RLT) using 177Lu-PSMA I&T resulted in over 97% destruction of metastatic tumors, indicating high efficacy of this treatment.

The study highlights the need for individualized dosimetry to account for variations in tumor response and suggests that measuring 177Lu-PSMA activity concentrations could improve routine dosimetry practices, while also noting that the first cycle of RLT has the most significant impact on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiomics Analysis for 177Lu-DOTAGA-(l-y)fk(Sub-KuE) Targeted Radioligand Therapy Dosimetry in Metastatic Prostate Cancer-A Model Based on Clinical Example. Kelk, E., Ruuge, P., Rohtla, K., et al.[2021]

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 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]

In a study involving 145 patients with metastatic castration-resistant prostate cancer (mCRPC), treatment with 177Lu-PSMA-617 showed a biochemical response rate of 45%, indicating high efficacy, especially with 40% of patients responding after just one treatment cycle.

The therapy demonstrated a favorable safety profile, with only 10% of patients experiencing severe hematotoxicity and 8% reporting dry mouth, suggesting it may be a safer option compared to other third-line treatments for mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. Rahbar, K., Ahmadzadehfar, H., Kratochwil, C., et al.[2022]

PSMA-TO-1 showed greater tumor uptake than PSMA-617 in both mice and human patients, suggesting it may be more effective for targeting prostate cancer.

While PSMA-TO-1 treatment led to significantly longer survival in mice compared to PSMA-617, it also resulted in higher radiation exposure to the kidneys, indicating a need for further studies to balance efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of PSMA-TO-1 and PSMA-617 labeled with gallium-68, lutetium-177 and actinium-225. Meyer, C., Prasad, V., Stuparu, A., et al.[2023]

In a study involving 270 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 (177Lu-PSMA), nomograms were developed to predict overall survival and PSA-progression-free survival based on various clinical and imaging factors, achieving a C-index of 0.71 for overall survival.

The nomograms effectively stratified patients into low-risk and high-risk groups, with low-risk patients showing significantly longer overall survival (24.9 months) compared to high-risk patients (7.4 months), indicating their potential utility in clinical decision-making and trial design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. Gafita, A., Calais, J., Grogan, TR., et al.[2021]

In a study of 135 prostate cancer patients, those with high tumor loads showed significantly reduced uptake of Ga-68-PSMA-11 in critical organs like the lacrimal and salivary glands, which could impact treatment planning for radioligand therapy (RLT).

The findings suggest that individualizing therapy protocols based on diagnostic PSMA PET imaging could enhance the efficacy and safety of Lu-177-labeled PSMA-ligand therapy, as reduced tracer uptake in dose-limiting organs may affect treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer. Gaertner, FC., Halabi, K., Ahmadzadehfar, H., et al.[2018]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9803619/

Therapeutic Outcomes of 177Lu-PSMA Targeted Therapy ... The outcomes of 177Lu-PSMA targeted therapy have demonstrated an acceptable response rate in the metastatic castration-resistant prostate cancer (mCRPC) (5). It ...

3. 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 complete response was observed in 9.3% of patients in the experimental arm, compared to none in the control arm. The best overall response was ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33687624/

Real-World Data Analysis of Efficacy and Survival After ... Our findings suggest that 177 Lu-PSMA radioligand therapy provides a significant response rate with a low toxicity profile.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.82

Survival outcomes of patients (pts) with metastatic ... Survival outcomes of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving lutetium-177-PSMA-617 (Lu) based on ...

6. 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 ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)03737-1/fulltext

1400P Efficacy and safety of 177Lu-PNT2002 prostate ... There was one death reported (non-treatment related) and 11 (42%) patients achieved a PSA50 response. Grade ≥3 treatment emergent adverse events (TEAEs) ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04647526

Study Evaluating mCRPC Treatment Using PSMA [Lu-177 ... The purpose of this study is to evaluate the efficacy and safety of [Lu-177]-PNT2002 in patients with metastatic castration-resistant prostate cancer.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.TPS5087

Study evaluating metastatic castrate resistant prostate ... This trial seeks to prospectively evaluate the efficacy of 177 Lu-PNT2002 for men with progressive mCRPC after androgen receptor axis-targeted (ARAT) therapy.