ONC-392 + Lutetium for Prostate Cancer

(PRESERVE-006 Trial)

Recruiting at 55 trial locations

Overseen By Martin Devenport, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 9

Duration: 12 months

141 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for prostate cancer that has spread and resisted other therapies. It examines the effectiveness of lutetium Lu 177 vipivotide tetraxetan, a targeted radioligand therapy, both alone and with varying doses of ONC-392. Men with prostate cancer that progresses despite certain treatments and who have a positive PSMA scan might be suitable for this study. The researchers aim to find a more effective treatment for those unresponsive to typical therapies. As a Phase 1 and Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in prostate cancer therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using ONC-392 with lutetium Lu 177 vipivotide tetraxetan is generally safe for patients with advanced prostate cancer that no longer responds to hormone therapy. In earlier studies, this treatment combination was usually well-tolerated, with promising results and few serious side effects.

ONC-392 targets cancer cells while sparing healthy ones. It aims to attack the tumor without causing much harm to the rest of the body, reducing unwanted side effects.

Lutetium Lu 177 vipivotide tetraxetan, when combined with ONC-392, has also undergone testing. It delivers radiation directly to cancer cells, protecting healthy tissues from radiation and usually resulting in fewer side effects.

In summary, research suggests that using ONC-392 and lutetium Lu 177 vipivotide tetraxetan together is reasonably safe. Previous patients tolerated it well, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach to tackling prostate cancer. ONC-392 is an innovative immunotherapy that works by enhancing the immune system's ability to fight cancer cells, potentially offering a new mechanism compared to traditional hormone therapies like androgen deprivation therapy (ADT) or chemotherapy. The combination with lutetium Lu 177 vipivotide tetraxetan, a targeted radioligand therapy, allows for precise delivery of radiation directly to cancer cells, minimizing damage to surrounding healthy tissue. This dual approach could provide a more effective treatment option for patients with advanced prostate cancer, setting it apart from existing options.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

This trial will evaluate the combination of ONC-392 with lutetium Lu 177 vipivotide tetraxetan for treating prostate cancer. Research shows that combining these treatments may hold promise. Participants will be assigned to one of three arms: Arm 1 will receive a low dose of ONC-392 plus lutetium Lu 177 vipivotide tetraxetan, Arm 2 will receive a high dose of ONC-392 plus lutetium Lu 177 vipivotide tetraxetan, and Arm 3 will receive lutetium Lu 177 vipivotide tetraxetan alone. Previous studies in patients with advanced prostate cancer unresponsive to hormone therapy have shown significant improvements in delaying disease progression and increasing overall survival when Lu 177 is combined with other treatments. This suggests that adding ONC-392 could be effective. The combination aims to leverage the strengths of both drugs, potentially offering better results for patients who have already tried other treatments. Early results are encouraging, but more research is needed to confirm the long-term benefits. ^{1 2 3 5 6}

Who Is on the Research Team?

David Wise, MD

Principal Investigator

NYU Langone Health

Mark N. Stein

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

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.

My heart doesn't work properly.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• lutetium Lu 177 vipivotide tetraxetan
• ONC-392

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.

How Is the Trial Designed?

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.

lutetium Lu 177 vipivotide tetraxetan is already approved in United States, European Union for the following indications:

Approved in United States as Pluvicto for:

• Prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC)

Approved in European Union as Pluvicto for:

• Prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC)

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5067

Phase 1 study of gotistobart (BNT316/ONC-392) in ... Background: When used in combination with physician's choice of care, Lu 177 showed significant PFS and OS improvements in mCRPC.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05682443

NCT05682443 | ONC-392 Plus Lutetium Lu 177 Vipivotide ... The goal of this clinical trial is to examine the safety and efficacy of ONC-392 in combination with lutetium Lu 177 vipivotide tetraxetan in metastatic ...

3. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-prostate-cancer/160813-asco-2025-preserve-006-phase-1-study-of-gotistobart-bnt316-onc-392-in-combination-with-lutetium-lu-177-vipivotide-tetraxetan-in-patients-with-mcrpc.html

PRESERVE-006: Phase 1 Study of Gotistobart (BNT316/ ... David Wise discussing a phase 1 study of gotistobart (BNT316/ONC-392) in combination with lutetium Lu 177 vipivotide tetraxetan in patients with metastatic ...

4. curetoday.com curetoday.com/view/first-patient-dosed-with-novel-combo-in-prostate-cancer-trial

First Patient Dosed With Novel Combo in Prostate Cancer ... The first patient has been dosed in a phase 1/2 trial evaluating a novel treatment combination of gotistobart (BNT316/ONC-392) and Pluvicto ...

5. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/randomized-study-onc-392-plus-lutetium-lu-177-vipivotide-tetraxetan-patients-metastatic-castration-resistant-prostate-cancer-mcrpc-who-progressed-androgen-receptor-ar-pathway-inhibition

Randomized Study of ONC-392 plus Lutetium Lu 177 ... The main purpose of the study is to determine whether the study drug, ONC-392, together with a standard of care drug PLUVICTO® (Lutetium Lu 177 Vipivotide ...

6. urotoday.com urotoday.com/video-lectures/mcrpc-treatment/video/mediaitem/4879-phase-i-trial-combines-onc-392-with-lutetium-177-for-prostate-cancer-david-wise.html

Phase I Trial Combines ONC-392 with Lutetium-177 for ... ONC-392 is a pH-sensitive CTLA-4 antibody designed to selectively deplete Tregs in tumor microenvironments while minimizing peripheral toxicity.