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Metastatic Castration-resistant Prostate CancerPhase 1/2PRESERVE-006NCT05682443

ONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With mCRPC

A Phase 1/2 study testing ONC-392 low, ONC-392 high and lutetium Lu 177 vipivotide tetraxetan in people with Metastatic Castration-resistant Prostate Cancer, run by OncoC4, Inc. at 23 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
ONC-392 low, ONC-392 high and lutetium Lu 177 vipivotide tetraxetan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
148 participants
Where
23 sitesUnited States
Study dates
11 Dec 2023to 30 Nov 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must be ≥ 18 years of age and have the ability to understand and sign an approved informed consent form (ICF).
  • Patients must have an ECOG performance status of 0 or 1.
  • Patients must have a life expectancy > 6 months.
  • Patients must have histological or cytological confirmation of prostate adenocarcinoma.
  • Patients must have a positive PSMA in an FDA-approved PSMA PET scan. A positive PSMA is defined as at least one tumor lesion with PSMA uptake greater than normal liver.
  • Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (< 50 ng/dL or < 1.7 nmol/L).
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  • Patients must have received at least one second generation AR-targeting agents (such as apalutamide, darolutamide, enzalutamide and/or abiraterone).
  • Patients should have prior treatment of up to two taxane regimens, or are unfit for, or refuse taxane chemotherapy. A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. Note: Taxane chemotherapy administered in the Castration Sensitive Prostate Cancer (CSPC) or Castration Resistant Prostate Cancer (CRPC) setting is allowed.
  • Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:
  • Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 1.0 ng/mL.
  • RECIST v1.1 soft-tissue progression
  • Progression of bone disease: 2 or more new metastatic bone lesions by bone scan per PCWG3 criteria.
  • Patients must have ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging obtained ≤ 42 days prior to beginning study therapy.
  • Patients must have adequate organ function.
  • Patients with or without concomitant bisphosphonate or denosumab regimen for ≥ 30 days prior to randomization are eligible.
  • For patients who have partners of childbearing potential: Partner and/or patient must use adequate methods of birth control with barrier protection, deemed acceptable by the principal investigator during the study and for 3 months after last study drug administration.

Who cannot join

  • Patients who have not recovered to NCI CTCAE grade ≤ 1 from an adverse event (AE) due to prior cancer therapeutics except neuropathy or endocrinopathy with Gr 2 or less.
  • Any systemic anti-cancer therapy within 5 half-lives or 14 days, whichever is shorter (small molecule drugs) or within 28 days for antibody based therapy, prior to starting study treatment.
  • Known hypersensitivity to the components of the study therapy or its analogs.
  • Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
  • Transfusion within 14 days of first day of study treatment
  • PSMA-negative lesions are defined as lesions with PSMA uptake equal to or lower than that of liver parenchyma. Patients with PSMA-negative lesions in any lymph node with a short axis of ≥ 2.5 cm, in any metastatic solid-organ lesions with a short axis of ≥ 1.0 cm, or in any metastatic bone lesion with a soft-tissue component of ≥ 1.0 cm in the short axis are ineligible.
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  • Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation within 6 months prior to randomization. Previous PSMA-targeted radioligand therapy is not allowed.
  • Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast).
  • A superscan as seen in the baseline bone scan.
  • Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
  • Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, myocardial infarction within 6 months, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, or unstable arrhythmia within 3 months, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
  • Active concurrent malignancy (with the exception of non-melanomatous skin cancer). Patients with carcinoma in situ of any origin and patients with prior malignancies who are in remission and/or whose likelihood of recurrence is very low per investigator's judgment are eligible for this study.
  • Receiving systemic steroid therapy with > 10 mg/day prednisone or equivalent within 7 days prior to the first dose of study treatment or receiving any other form of immunosuppressive medication.
  • Active GI disease, including peptic ulcer disease, pancreatitis, diverticulitis, or inflammatory bowel disease.
  • Active or previously documented autoimmune disease and/or current use of immunosuppressive agents. Use of endocrine replacement therapy (e.g., thyroxine, insulin, low dose of steroid, etc.) is allowed.

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

United States23 sites

  • New Mexico Oncology Hematology Consultants

    Albuquerque, New Mexico, 87109

  • Emory University Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Rocky Mountain Cancer Centers USOR

    Aurora, Colorado, 80012

  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21202

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14203

  • Lahey Hospital & Medical Center

    Burlington, Massachusetts, 01805

  • UNC North Carolina Comprehensive Cancer Care Center

    Chapel Hill, North Carolina, 27514

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Duke Cancer Center

    Durham, North Carolina, 27710

  • Virginia Cancer Specialists USOR

    Fairfax, Virginia, 22031

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • UW Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Rutgers Cancer Institute

    New Brunswick, New Jersey, 08901

  • NYU Langone Health, Laura & Isaac Perlmutter Cancer Center

    New York, New York, 10016

  • Columbia University Irving Cancer Center

    New York, New York, 10032

  • Virginia Oncology Associates USOR

    Norfolk, Virginia, 23502

  • Oncology and Hematology Associates Of Southwest Virginia USOR

    Norton, Virginia, 24273

  • XCancer/GU Research Network

    Omaha, Nebraska, 68130

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97210

  • UC Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Moffitt Cancer Cancer

    Tampa, Florida, 33612

  • Chesapeake Urology Research Associates

    Towson, Maryland, 21204

Other trials in United States

About this study

Official title: Randomized Study of ONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Progressed on Androgen Receptor (AR) Pathway Inhibition

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.

Read the detailed description

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 castration resistant prostate cancer patient who have disease progressed on androgen receptor pathway inhibition. The main questions it aims to answer are (1) whether it is safe to combine ONC-392 with lutetium Lu 177 vipivotide tetraxetan, (2) whether the combination increases the radiographic progression free survival (rPFS).

In Phase 1 of the trial, participates will be randomized to experimental arm and control arm in 2:1 ratio. In experimental arm, they will be given ONC-392 IV infusion for up to 9 cycles or approximately one year, together with lutetium Lu 177 vipivotide tetraxetan for up to 6 cycles. In Phase 2 of the trial, participants will be randomized to three arms in 1:1:1 ratio. There will be two experimental arms, one with low dose of ONC-392 and one with high dose ONC-392, to be given in IV infusion for up to 9 or 13 cycles or approximately one year, together with lutetium Lu 177 vipivotide tetraxetan for up to 6 cycles. In active control arm for both Phase 1 and Phase 2, participants will be given standard of care treatment with lutetium Lu 177 vipivotide tetraxetan for up to 6 cycles.

Being tested
ONC-392 low, ONC-392 high, lutetium Lu 177 vipivotide tetraxetan

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ONC-392 lowDrug

    Also called A humanized anti-CTLA4 IgG1 monoclonal antibody, Gotistobart

    ONC-392 will be given as IV infusion, Q4W for up to 13 doses.

  • ONC-392 highDrug

    Also called A humanized anti-CTLA4 IgG1 monoclonal antibody, Gotistobart

    ONC-392 will be given as IV infusion, Q6W for up to 9 doses.

  • lutetium Lu 177 vipivotide tetraxetanDrug

    Also called Pluvicto

    lutetium Lu 177 vipivotide tetraxetan will be given as IV infusion, Q6W, for up to 6 doses.

Study groups in NCT05682443
Study groupRoleWhat they receive
Arm 1: ONC-392 low dose plus lutetium Lu 177 vipivotide tetraxetanExperimentalArm 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.
Receives: Drug: ONC-392 low; Drug: lutetium Lu 177 vipivotide tetraxetan
Arm 2: ONC-392 high dose plus lutetium Lu 177 vipivotide tetraxetanExperimentalArm 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.
Receives: Drug: ONC-392 high; Drug: lutetium Lu 177 vipivotide tetraxetan
Arm 3: lutetium Lu 177 vipivotide tetraxetanActive comparatorArm 3 receives lutetium Lu 177 vipivotide tetraxetan, IV infusion, Q6W for up to 6 doses.
Receives: Drug: lutetium Lu 177 vipivotide tetraxetan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. DLT (Dose escalation Phase 1)

    Incidence of dose-limiting toxicity (DLT).

    Measured: 40 months

  2. PSA50 (Dose Expansion Phase 2)

    Dual primary endpoints: PSA50 and rPFS assessed by investigators.

    Measured: 40 months

  3. rPFS (Dose Expansion Phase 2)

    Dual primary endpoints: PSA50 and rPFS assessed by investigators.

    Measured: 40 months

  4. TEAEs and irAEs (Dose Expansion Phase 2)

    Incidence of TEAEs, irAEs, and TEAEs leading to study treatment discontinuation.

    Measured: 40 months

Secondary outcomes (4)

  1. PSA progression free survival

    PSA progression free survival as defined by PCWG3 guideline.

    Measured: 40 months

  2. Composite progression-free survival (PFS)

    The PFS event is defined as either radiographic progression, or PSA increase by PCWG3 guideline, or death, whichever comes first.

    Measured: 40 months

  3. Overall survival (OS)

    The length of time patients live after starting treatment.

    Measured: 40 months

  4. Response rate

    Response rate based on radiographic evaluation of PCWG3.

    Measured: 40 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2023
  2. Study start11 Dec 2023
  3. Primary completion30 Nov 2026 (estimated)
  4. Study completion30 Nov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, open label, active controlled, multi-center study
Masking
None (open label)
Enrolment
148 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05682443
Sponsor's protocol ID
PRESERVE-006
Acronym
PRESERVE-006
Status last verified
May 2026
First submitted
26 Dec 2022
Last updated
22 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ONC-392 low, ONC-392 high and lutetium Lu 177 vipivotide tetraxetan in people with Metastatic Castration-resistant Prostate Cancer, run by OncoC4, Inc. at 23 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

DLT (Dose escalation Phase 1) (time frame: 40 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05682443.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.

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