MT218 Injection for Prostate Cancer

Overseen By David M Schuster, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Molecular Theranostics LLC

Disqualifiers: Kidney disease, Liver disease, Diabetes, Hypertension, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase 1b open label, dose-escalating investigation study is to evaluate the dose dependent initial efficacy of the use of MT218 injection for biomarker targeted MR molecular imaging (MRMI) of prostate cancer in patients scheduled for radical prostatectomy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking any MRI contrast agents, you must not have received them within 48 hours before or 24 hours after the MT218 injection.

What data supports the effectiveness of the drug MT218 injection for prostate cancer?

Research on similar peptide-drug conjugates shows that they can specifically target prostate cancer cells and improve drug delivery, leading to higher uptake in cancer cells and significant tumor accumulation. This suggests that MT218, which is also a peptide conjugate, might effectively target and treat prostate cancer. ^{1 2 3 4 5}

What makes the MT218 injection drug unique for prostate cancer treatment?

The MT218 injection is unique because it uses a Gd(HP-DO3A) conjugated peptide that targets prostate cancer cells specifically, potentially improving drug delivery and effectiveness compared to traditional treatments. This approach may enhance the concentration of the drug in the tumor while minimizing effects on other tissues. ^{2 3 5 6 7}

Research Team

David Schuster, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for men with prostate cancer who are scheduled to have their prostate removed. It's an early-phase study, so they're looking for people who haven't had this kind of imaging before.

Inclusion Criteria

Patients must be able to provide written informed consent

My kidney function is good, with a GFR over 60 mL/min.

I can stay still for an MRI scan.

Exclusion Criteria

Patients with uni- or bilateral hip prosthesis

Patients with contraindications for MRI including implantable pace makers, cochlear implants

Is determined by the investigator that the patient is clinically unsuitable for the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous injection of MT218 and undergo MR imaging

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 days

1 visit (in-person)

Treatment Details

Interventions

• MT218 injection

Trial Overview The study tests different doses of a new MRI contrast agent called MT218 to see how well it shows prostate cancer on scans. This is done just before patients have surgery to remove the prostate.

Participant Groups

Group I: MT218 Experimental Treatment 1 Intervention

Each patient will receive a single intravenous injection of MT218 while being scanned with standard MR imaging sequences/protocol. The first cohort of four subjects will receive 0.02 mmol/kg, second cohort of four subjects will receive 0.04 mmol/kg, and third cohort of four subjects will receive 0.06 mmol/kg of MT218.

Who Is Running the Clinical Trial?

Molecular Theranostics LLC

Lead Sponsor

Trials

1

Recruited

10+

Songqi Gao

Lead Sponsor

Trials

1

Recruited

10+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Findings from Research

In a study involving 26 prostate cancer patients (14 with biochemically recurrent and 12 with metastatic hormone-refractory cancer), personalized peptide vaccination successfully enriched T cells reactive to multiple tumor-associated antigens (TAAs) after a 2-week culture period.

The approach demonstrated that priming lymphocytes with TAAs-derived peptides led to the development of polyclonal effector CD8+ T cells, indicating its potential as a viable strategy for T cell immunotherapy in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized ex vivo multiple peptide enrichment and detection of T cells reactive to multiple tumor-associated antigens in prostate cancer patients. Taborska, P., Stakheev, D., Strizova, Z., et al.[2021]

TGX-221, a potent PI3Kβ inhibitor, has been modified into a peptide-drug conjugate that specifically targets HER2 overexpressing prostate cancer cells, enhancing its delivery and effectiveness.

The peptide-drug conjugate showed significantly higher cellular uptake in prostate cancer cells compared to the original drug, and both the conjugate and its cleaved products maintained similar activity to TGX-D1, indicating its potential as an effective chemotherapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a peptide-drug conjugate for prostate cancer therapy. Tai, W., Shukla, RS., Qin, B., et al.[2021]

The enzyme-responsive peptide drug conjugate developed for TGX-D1, a PI3K inhibitor, shows improved cellular uptake in prostate cancer cells by about nine times, enhancing its potential efficacy in treatment.

This conjugate is designed to remain stable in the bloodstream of prostate cancer patients but can be cleaved by high levels of prostate-specific antigen (PSA) in the tumor microenvironment, allowing for targeted delivery and significant accumulation in tumors while minimizing distribution to other tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An enzyme-responsive conjugate improves the delivery of a PI3K inhibitor to prostate cancer. Barve, A., Jain, A., Liu, H., et al.[2018]

L-377202, a novel peptide conjugate of doxorubicin, was well tolerated in 19 patients with advanced hormone-refractory prostate cancer, with a recommended dose of 225 mg/m² established for further efficacy studies.

The drug was successfully metabolized into active forms, leucine-doxorubicin and doxorubicin, and showed promising results with some patients experiencing significant decreases in PSA levels, indicating potential effectiveness in treating prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of a novel prostate-specific antigen-activated peptide-doxorubicin conjugate in patients with prostate cancer. DiPaola, RS., Rinehart, J., Nemunaitis, J., et al.[2016]

In a study using nude mice with human prostate cancer, combining the radiation therapy 90Y-DOTA-peptide-ChL6 with docetaxel resulted in a 67% cure rate, while the combination with paclitaxel achieved a 100% response rate with 20% cures, indicating significant therapeutic synergy.

The addition of these chemotherapy drugs did not increase toxicity compared to radiation therapy alone, suggesting that this combined treatment approach could be safely translated to clinical settings for improved prostate cancer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modality radioimmunotherapy for human prostate cancer xenografts with taxanes and 90yttrium-DOTA-peptide-ChL6. O'Donnell, RT., DeNardo, SJ., Miers, LA., et al.[2019]

The pilot study involving 12 patients with locally advanced prostate cancer demonstrated that the immunotherapy D17DT was well tolerated and led to significant reductions in serum testosterone and PSA levels in some patients.

Four patients achieved castrate levels of testosterone that were maintained for up to 9 months, suggesting that immunizing against GnRH could be an effective alternative to traditional hormonal therapies, especially in those with higher anti-GnRH antibody titres.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer. Simms, MS., Scholfield, DP., Jacobs, E., et al.[2018]

In a study of 31 men with recurrent prostate cancer, (68)Ga-PSMA-11 PET/CT showed a detection rate of 71%, indicating its efficacy in identifying cancer recurrence, especially in patients with higher PSA levels.

The study found a moderate correlation between PSA levels and both the number of lesions detected and the uptake of the radiotracer in cancerous lesions, suggesting that (68)Ga-PSMA-11 can be a useful tool for monitoring disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(68)Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer. Sachpekidis, C., Eder, M., Kopka, K., et al.[2021]

References

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

Personalized ex vivo multiple peptide enrichment and detection of T cells reactive to multiple tumor-associated antigens in prostate cancer patients. [2021]

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

Development of a peptide-drug conjugate for prostate cancer therapy. [2021]

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

An enzyme-responsive conjugate improves the delivery of a PI3K inhibitor to prostate cancer. [2018]

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

Characterization of a novel prostate-specific antigen-activated peptide-doxorubicin conjugate in patients with prostate cancer. [2016]

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

Combined modality radioimmunotherapy for human prostate cancer xenografts with taxanes and 90yttrium-DOTA-peptide-ChL6. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

(68)Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer. [2021]