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

NCT05682443 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: PRESERVE-006
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 23

Brief 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.

Conditions

Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (4)

• DLT (Dose escalation Phase 1)

  Incidence of dose-limiting toxicity (DLT).

  40 months

• PSA50 (Dose Expansion Phase 2)

  Dual primary endpoints: PSA50 and rPFS assessed by investigators.

  40 months

• rPFS (Dose Expansion Phase 2)

  Dual primary endpoints: PSA50 and rPFS assessed by investigators.

  40 months

• TEAEs and irAEs (Dose Expansion Phase 2)

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

  40 months

Secondary Outcomes (4)

• PSA progression free survival

  40 months

• Composite progression-free survival (PFS)

  40 months

• Overall survival (OS)

  40 months

• Response rate

  40 months

Study Arms (3)

Arm 1: ONC-392 low dose plus lutetium Lu 177 vipivotide tetraxetan

EXPERIMENTAL

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.

Drug: ONC-392 low; Drug: lutetium Lu 177 vipivotide tetraxetan

Arm 2: ONC-392 high dose plus lutetium Lu 177 vipivotide tetraxetan

EXPERIMENTAL

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.

Drug: ONC-392 high; Drug: lutetium Lu 177 vipivotide tetraxetan

Arm 3: lutetium Lu 177 vipivotide tetraxetan

ACTIVE COMPARATOR

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

Drug: lutetium Lu 177 vipivotide tetraxetan

Interventions

ONC-392 low DRUG

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

Also known as: A humanized anti-CTLA4 IgG1 monoclonal antibody, Gotistobart

Arm 1: ONC-392 low dose plus lutetium Lu 177 vipivotide tetraxetan

ONC-392 high DRUG

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

Also known as: A humanized anti-CTLA4 IgG1 monoclonal antibody, Gotistobart

Arm 2: ONC-392 high dose plus lutetium Lu 177 vipivotide tetraxetan

lutetium Lu 177 vipivotide tetraxetan DRUG

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

Also known as: Pluvicto

Arm 1: ONC-392 low dose plus lutetium Lu 177 vipivotide tetraxetan; Arm 2: ONC-392 high dose plus lutetium Lu 177 vipivotide tetraxetan; Arm 3: lutetium Lu 177 vipivotide tetraxetan

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• OncoC4, Inc.: lead
• Prostate Cancer Clinical Trials Consortium: collaborator

Study Sites (23)

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Rocky Mountain Cancer Centers USOR

Aurora, Colorado, 80012, United States

Location

Moffitt Cancer Cancer

Tampa, Florida, 33612, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21202, United States

Location

Chesapeake Urology Research Associates

Towson, Maryland, 21204, United States

Location

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

XCancer/GU Research Network

Omaha, Nebraska, 68130, United States

Location

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901, United States

Location

New Mexico Oncology Hematology Consultants

Albuquerque, New Mexico, 87109, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

NYU Langone Health, Laura & Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Columbia University Irving Cancer Center

New York, New York, 10032, United States

Location

UNC North Carolina Comprehensive Cancer Care Center

Chapel Hill, North Carolina, 27514, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97210, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Virginia Cancer Specialists USOR

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates USOR

Norfolk, Virginia, 23502, United States

Location

Oncology and Hematology Associates Of Southwest Virginia USOR

Norton, Virginia, 24273, United States

Location

UW Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

Pluvicto

Study Officials

• David Wise, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

• Mark Stein, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, open label, active controlled, multi-center study

Study Record Dates

• First Submitted: December 26, 2022
• First Posted: January 12, 2023
• Study Start: December 11, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (23)