ONC-392 + Lutetium for Prostate Cancer

(PRESERVE-006 Trial)

Recruiting at 54 trial locations

Overseen By Pan Zheng, MD, PhD

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: OncoC4, Inc.

Must be taking: Androgen-deprivation therapy

Must not be taking: Cytotoxic chemotherapy, Immunotherapy

Disqualifiers: CNS metastases, Active hepatitis, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

In this Phase 2 study, mCRPC patients with PSMA positive scans who progressed on prior ARTA and up to 2 lines of taxanes, and are naïve to lutetium Lu 177 vipivotide tetraxetan, will be enrolled. The study is open-label, randomized with active control, multi-center study.

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 cannot have any systemic anti-cancer therapy within 14 to 28 days before starting the study treatment, depending on the type of medication.

What data supports the effectiveness of the drug Lutetium Lu 177 vipivotide tetraxetan for prostate cancer?

The drug Lutetium Lu 177 vipivotide tetraxetan was shown to improve overall survival in patients with prostate cancer in a large clinical trial called VISION. Patients who received the drug lived a median of 15.3 months compared to 11.3 months for those who did not receive it, showing a significant benefit. ^{1 2 3 4 5}

Is the treatment with ONC-392 + Lutetium safe for humans?

Lutetium Lu 177 vipivotide tetraxetan, also known as Pluvicto, has been approved by the FDA for treating a specific type of prostate cancer, indicating it has been evaluated for safety in humans. It targets cancer cells with radiation, which can cause side effects, but its approval suggests that the benefits outweigh the risks for the approved use. ^{1 2 3 5 6}

What makes the drug Lutetium Lu 177 vipivotide tetraxetan unique for prostate cancer treatment?

Lutetium Lu 177 vipivotide tetraxetan is unique because it is the first FDA-approved targeted radioligand therapy for prostate cancer, specifically targeting prostate-specific membrane antigen (PSMA) on cancer cells to deliver radiation directly, minimizing damage to normal tissues. ^{1 2 3 5 6}

Research Team

David Wise, MD

Principal Investigator

NYU Langone Health

Mark N. Stein

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for adults with metastatic prostate cancer resistant to castration who've progressed on androgen receptor inhibitors, have had prior taxane treatments (up to two), and show a positive PSMA PET/CT scan. They should be in good health overall, with an ECOG score of 0 or 1, adequate organ function, and no other recent cancers or severe illnesses.

Inclusion Criteria

Patients must have a positive PSMA PET/CT scan

I have at least one cancer spread that shows on scans taken within the last 28 days.

I have been treated with medications like enzalutamide or abiraterone.

Exclusion Criteria

I have recovered from side effects of previous cancer treatments.

I am not on more than 10 mg/day of prednisone or any immunosuppressive medication.

I haven't had certain radiation treatments in the last 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ONC-392 IV infusion for up to 9 cycles and lutetium Lu 177 vipivotide tetraxetan for up to 6 cycles

12 months

Up to 9 visits (in-person) for ONC-392, up to 6 visits (in-person) for lutetium Lu 177 vipivotide tetraxetan

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• lutetium Lu 177 vipivotide tetraxetan (Other)
• ONC-392 (Other)

Trial Overview The study tests ONC-392 combined with lutetium Lu 177 vipivotide tetraxetan against standard care using only lutetium Lu 177. Patients are randomly assigned in a 2:1 ratio to either receive both drugs together or just the standard treatment to see if the combination improves survival without disease progression.

Participant Groups

Group I: Arm 2: ONC-392 high dose plus lutetium Lu 177 vipivotide tetraxetan Experimental Treatment 2 Interventions

Arm 2 receives ONC-392 6 mg/kg, IV infusion, Q6W for up to 9 doses, plus lutetium Lu 177 vipivotide tetraxetan IV infusion, Q6W for up to 6 doses.

Group II: Arm 1: ONC-392 low dose plus lutetium Lu 177 vipivotide tetraxetan Experimental Treatment 2 Interventions

Arm 1 receives ONC-392 3 mg/kg, IV infusion, Q4W for up to 13 doses, plus lutetium Lu 177 vipivotide tetraxetan IV infusion, Q6W for up to 6 doses.

Group III: Arm 3: lutetium Lu 177 vipivotide tetraxetan Active Control 1 Intervention

Arm 3 receives lutetium Lu 177 vipivotide tetraxetan, IV infusion, Q6W for up to 6 doses.

Who Is Running the Clinical Trial?

OncoC4, Inc.

Lead Sponsor

Trials

8

Recruited

1,800+

Prostate Cancer Clinical Trials Consortium

Collaborator

Trials

12

Recruited

7,400+

Findings from Research

Lutetium Lu 177 vipivotide tetraxetan (PLUVICTO™) is a targeted radioligand therapy approved in the USA for treating metastatic castration-resistant prostate cancer (mCRPC) that expresses prostate-specific membrane antigen (PSMA), based on positive results from the phase 3 VISION trial.

This therapy specifically targets PSMA, which is overexpressed in prostate cancer cells, allowing for a more effective treatment option for patients who have already undergone other therapies like androgen receptor inhibition and taxane-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. Keam, SJ.[2022]

177Lu-vipivotide tetraxetan is a targeted radiopharmaceutical that effectively treats metastatic castration-resistant prostate cancer (mCRPC) by delivering beta-radiation directly to cancer cells, demonstrating safety and tolerability in clinical trials.

Approved by the FDA in March 2022 based on the VISION trial, this therapy is particularly beneficial for patients who have already undergone androgen receptor pathway inhibition and taxane-based chemotherapy, highlighting its role as a new treatment option in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer. Shah, H., Ravi, P., Sonpavde, G., et al.[2023]

The FDA approved Pluvicto (177Lu-PSMA-617) for treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have undergone prior treatments, showing a significant improvement in overall survival (15.3 months vs. 11.3 months with standard care) in a trial with 831 participants.

Common side effects of Pluvicto include fatigue, dry mouth, and nausea, with notable laboratory abnormalities such as decreased lymphocytes and hemoglobin occurring in over 30% of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. Fallah, J., Agrawal, S., Gittleman, H., et al.[2023]

In a phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of [177Lu]Lu-PSMA-617 to standard care significantly delayed the time to first symptomatic skeletal event, with a median of 11.5 months compared to 6.8 months for standard care alone.

Patients receiving [177Lu]Lu-PSMA-617 also reported improved health-related quality of life and less pain, although there were some serious adverse events, including hematological issues, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. Fizazi, K., Herrmann, K., Krause, BJ., et al.[2023]

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is an approved treatment for adult patients with advanced prostate cancer that expresses the prostate-specific membrane antigen (PSMA).

This therapy is specifically indicated for patients who have already undergone treatment with androgen receptor pathway inhibitors and taxane-based chemotherapy, highlighting its role in later-stage cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Metastatic Castration-Resistant Prostate Cancer. Aschenbrenner, DS.[2022]

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is the first FDA-approved targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC), specifically for patients with high levels of prostate-specific membrane antigen (PSMA).

This treatment works by binding to PSMA, which is overexpressed in prostate cancer cells, allowing targeted radiation to damage DNA and induce cell death, making it a promising option in precision medicine for individualized cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. Liu, X., Fang, GC., Lu, H., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer. [2023]

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

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. [2023]

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

New Drug for Metastatic Castration-Resistant Prostate Cancer. [2022]

6. Spain pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. [2023]