PSMA-Targeted Trillium Compounds + PTI-122 for Prostate Cancer

Recruiting at 4 trial locations

Overseen By Gretchen Richards, MS

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: Ratio Therapeutics, Inc.

Must be taking: Hormone therapy

Must not be taking: PSMA-targeted therapy

Disqualifiers: Other malignancy, Significant illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 week

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests special compounds that target prostate cancer cells in men with advanced disease. These compounds are labeled with a radioactive substance to track them in the body and are tested with and without a protective agent to see if it reduces side effects.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not be on any PSMA-targeted therapy and should not be participating in another active treatment trial.

What data supports the effectiveness of the PSMA-Targeted Trillium Compounds + PTI-122 treatment for prostate cancer?

Research shows that targeting prostate-specific membrane antigen (PSMA) with radiolabeled compounds is promising for treating prostate cancer, as PSMA is highly expressed in prostate cancer cells. Similar treatments using PSMA-targeted radiopharmaceuticals, like 177Lu-PSMA-617, have shown effectiveness in advanced prostate cancer, suggesting potential for the PSMA-Targeted Trillium Compounds + PTI-122 treatment. ^{1 2 3 4 5}

What safety data exists for PSMA-targeted treatments in prostate cancer?

Some PSMA-targeted treatments, like the 211At-labeled agent, have shown limited and acceptable toxicity in studies, with little off-target effects and stable blood cell counts. Another study on 212Pb-based treatment found the kidney to be the dose-limiting organ, indicating some potential for kidney-related side effects. ^{4 6 7 8 9}

What makes the PSMA-Targeted Trillium Compounds + PTI-122 treatment unique for prostate cancer?

This treatment is unique because it uses a PSMA-targeted radiopharmaceutical with an optimized linker for better tumor uptake and reduced side effects, and it is radiolabeled with indium-111, which is different from other treatments that often use different isotopes like lutetium-177 or actinium-225. ^{4 5 7 9 10}

Research Team

John Babich, PhD

Principal Investigator

Ratio Therapeutics, Inc.

Eligibility Criteria

Inclusion Criteria

You have undergone a minimum of 30 days' androgen deprivation hormone therapy or another form of hormonal treatment, or are to commence such therapies in the near future.

If you have not had a prior PSMA PET scan, it may be provided as part of the study if you are eligible and have at least two PSMA positive lesions with one soft tissue lesion having an absolute minimum diameter of fifteen millimeters.

You have an Eastern Cooperative Oncology Group performance score between 0 and 2.

Exclusion Criteria

Serum creatinine > 1.5 mg/dL or creatinine clearance ≤50 mL/min by Cockcroft-Gault estimation

Significant intercurrent illness, treatment-related toxicity, or psychiatric illness/social situation that could place the subject at undue risk during study participation, significantly alter study outcomes, or affect subject compliance with study requirements for dosing and evaluation, as determined by the investigator

You are not currently receiving treatment for any other type of cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of PSMA-Targeted [In-111]-Labeled Trillium Compound, with or without PTI-122

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including imaging and blood tests

24 weeks

Multiple visits (in-person)

Treatment Details

Interventions

• PSMA-Targeted [In-111]-Labeled Trillium Compound
• PTI-122

Participant Groups

Group I: Trillium Compound Alone Experimental Treatment 1 Intervention

Single dose of PSMA-Targeted \[In-111\]-Labeled Trillium Compound

Group II: Trillium Compound + Single Dose PTI-122 Experimental Treatment 2 Interventions

Single dose of PSMA-Targeted \[In-111\]-Labeled Trillium Compound plus single dose of PTI-122 at 5, 10 or 15 mg

Group III: Trillium Compound + Multiple Dose PTI-122 Experimental Treatment 2 Interventions

Single dose of PSMA-Targeted \[In-111\]-Labeled Trillium Compound plus two doses of PTI-122 at the preferred dose level

Who Is Running the Clinical Trial?

Ratio Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

20+

Ratio Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

The FDA has approved 177Lu-PSMA-617 for treating advanced metastatic castrate-resistant prostate cancer (mCRPC), marking a significant advancement in PSMA-targeted therapies.

Various PSMA-targeted radiopharmaceuticals, including both beta and alpha emitters, are in development, with promising results for alpha therapies like 225Ac-PSMA-617, although there are concerns about potential toxicity to salivary and renal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate specific membrane antigen binding radiopharmaceuticals: Current data and new concepts. Sartor, O., Baghian, A.[2022]

Prostate-specific membrane antigen (PSMA) is a promising target for developing radiopharmaceuticals in treating aggressive prostate cancers, with ongoing clinical trials focusing on PSMA-targeted therapies, particularly using the β-particle-emitting radioisotope 177Lu.

PSMA PET imaging is crucial for evaluating tumor PSMA expression, helping to select the right patients for PSMA-targeted therapies, and studies are exploring PET parameters as predictive and prognostic biomarkers for treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of PET to Appropriately Select Patients for PSMA-Targeted Theranostics. Eshghi, A., Covington, MF., Eshghi, N., et al.[2023]

The new 211At-labeled radiotracer, 211At-3-Lu, effectively targets prostate-specific membrane antigen (PSMA) in prostate cancer cells, showing significant uptake in PSMA+ tumors with minimal uptake in non-target cells, indicating its potential for targeted therapy.

In a long-term toxicity study, 211At-3-Lu demonstrated low off-target toxicity and favorable safety profiles, including stable hematopoietic function and positive histopathological outcomes, suggesting it could be a safe and effective treatment option for patients with prostate cancer resistant to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Improved 211At-Labeled Agent for PSMA-Targeted &#945;-Therapy. Mease, RC., Kang, CM., Kumar, V., et al.[2022]

References

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

Synthesis and preliminary evaluation of 211At-labeled inhibitors of prostate-specific membrane antigen for targeted alpha particle therapy of prostate cancer. [2022]

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

Radiolabeled enzyme inhibitors and binding agents targeting PSMA: Effective theranostic tools for imaging and therapy of prostate cancer. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Current Status of Radiolabeled Monoclonal Antibodies Targeting PSMA for Imaging and Therapy. [2023]

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

Prostate specific membrane antigen binding radiopharmaceuticals: Current data and new concepts. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Current Status of PSMA-Radiotracers for Prostate Cancer: Data Analysis of Prospective Trials Listed on ClinicalTrials.gov. [2020]

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

Preclinical Evaluation of 203/212Pb-Labeled Low-Molecular-Weight Compounds for Targeted Radiopharmaceutical Therapy of Prostate Cancer. [2022]

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

Utility of PET to Appropriately Select Patients for PSMA-Targeted Theranostics. [2023]

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

An Improved 211At-Labeled Agent for PSMA-Targeted &#945;-Therapy. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Mono- and multimeric PSMA-targeting small molecule-thorium-227 conjugates for optimized efficacy and biodistribution in preclinical models. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of a PSMA-Targeting Homodimer with an Optimized Linker for Imaging of Prostate Cancer. [2023]