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

Trial Summary

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.

What data supports the effectiveness of the treatment 177Lu-PNT2002 for cancer?

Research shows that similar treatments using 177Lu, like 177Lu-PSMA-617, have been effective in treating advanced prostate cancer by improving survival rates and controlling disease progression. This suggests that 177Lu-PNT2002, which also targets prostate-specific membrane antigen (PSMA), may have similar benefits. ^{1 2 3 4 5}

Is 177Lu-PSMA safe for humans?

Studies on 177Lu-PSMA, including 177Lu-PNT2002, have shown that it is generally safe for use in humans, with toxicity levels being evaluated in patients with advanced prostate cancer. The treatment has been tested in various clinical settings, and while side effects can occur, they are typically manageable. ^{2 3 4 6 7}

How is the drug 177Lu-PNT2002 different from other treatments for prostate cancer?

177Lu-PNT2002 is unique because it is a radiolabeled small molecule that specifically targets prostate-specific membrane antigen (PSMA) on cancer cells, delivering targeted radiation to the tumor. This approach combines with stereotactic body radiotherapy (SBRT) to enhance treatment efficacy for oligorecurrent metastatic hormone-sensitive prostate cancer, offering a novel mechanism compared to traditional therapies. ^{1 2 3 8 9}

What is the purpose of this trial?

This is a single arm trial with one Cohort for people with recurrent or metastatic adenoid cystic carcinoma that cannot be treated with surgery. 10 participants will be enrolled in Cohort 1 at Johns Hopkins and will undergo DCFPyL PET/CT and 177Lu-PSMA dosimetry imaging only (single tracer dose). A feasibility analysis of dosimetry will be performed after meeting the accrual goal of Cohort 1 to determine if the study will proceed into Cohort 2. If Cohort 2 proceeds, based on the dosimetry analysis, the major requirements of the study are to undergo treatment with 177Lu-PNT2002, have bloodwork, physical exams, and imaging done at study-specific time points, and to answer questionnaires. Patients will be in the study for about two years after enrolling.

Research Team

Ana Kiess, MD, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

177Lu-labeled low-molecular-weight agents for PSMA-targeted radiopharmaceutical therapy. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks. [2021]

3. England 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). [2023]

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

Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer. [2021]

5. Switzerland 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. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Comparison of PSMA-TO-1 and PSMA-617 labeled with gallium-68, lutetium-177 and actinium-225. [2023]

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

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer. [2018]

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

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. [2022]

9. England 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. [2021]