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Combining ONC-392 with Lutetium Lu 177 for advanced prostate cancer

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

Phase1; Phase2 Interventional OncoC4, Inc. · NCT05682443

This study is testing if a new treatment combining ONC-392 with lutetium Lu 177 can help men with advanced prostate cancer live longer without their cancer getting worse.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment141 (estimated)
Ages18 Years and up
SexMale
SponsorOncoC4, Inc. Industry-sponsored
Drugs / interventionsdenosumab, chemotherapy, immunotherapy, prednisone
Locations23 sites (Sacramento, California and 22 other locations)
Trial IDNCT05682443 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of ONC-392 in combination with lutetium Lu 177 vipivotide tetraxetan in patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously progressed on androgen receptor pathway inhibitors. The study is open-label and randomized, with participants assigned to either experimental or control arms. In Phase 1, patients will receive ONC-392 along with lutetium Lu 177 for up to one year, while Phase 2 will explore different doses of ONC-392 in combination with the same treatment. The primary goal is to determine if this combination improves radiographic progression-free survival.

Who should consider this trial

Good fit: Ideal candidates are adults with metastatic castration-resistant prostate cancer who have previously received specific treatments and have positive PSMA scans.

Not a fit: Patients who have not undergone prior androgen receptor-targeting agents or taxane chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced prostate cancer who have limited treatment alternatives.

How similar studies have performed: Other studies have shown promise with similar combinations, but this specific approach is novel in its application.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Patients must be ≥ 18 years of age and have the ability to understand and sign an approved informed consent form (ICF).
2. Patients must have an ECOG performance status of 0 or 1.
3. Patients must have a life expectancy \> 6 months.
4. Patients must have histological or cytological confirmation of prostate adenocarcinoma.
5. 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.
6. 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).
7. Patients must have received at least one second generation AR-targeting agents (such as apalutamide, darolutamide, enzalutamide and/or abiraterone).
8. 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.
9. Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:

   1. 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.
   2. RECIST v1.1 soft-tissue progression
   3. Progression of bone disease: 2 or more new metastatic bone lesions by bone scan per PCWG3 criteria.
10. 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.
11. Patients must have adequate organ function.
12. Patients with or without concomitant bisphosphonate or denosumab regimen for ≥ 30 days prior to randomization are eligible.
13. 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.

Exclusion Criteria:

1. 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.
2. 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.
3. Known hypersensitivity to the components of the study therapy or its analogs.
4. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
5. Transfusion within 14 days of first day of study treatment
6. 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.
7. 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.
8. 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).
9. A superscan as seen in the baseline bone scan.
10. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
11. 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.
12. 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.
13. 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.
14. Active GI disease, including peptic ulcer disease, pancreatitis, diverticulitis, or inflammatory bowel disease.
15. 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.

Where this trial is running

Sacramento, California and 22 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Castration-resistant Prostate Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.