Clinical trial NCT05682443: ONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With mCRPC
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Castration-resistant Prostate Cancer
Lead sponsor: OncoC4, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Prostate Cancer Clinical Trials Consortium
First posted: 2023-01-12
Enrollment: 141
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, open label, active controlled, multi-center study
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: PSA50
timeFrame: 30 months
measure: TEAEs and irAEs
timeFrame: 30 months
Secondary outcomes:
measure: Composite radiographic progression-free survival (PFS)
timeFrame: 30 months
measure: Composite progression-free survival (PFS)
timeFrame: 30 months
measure: Overall survival (OS)
timeFrame: 30 months
measure: Response rate
timeFrame: 30 months
measure: DoR (Duration of Response) and DCR (Disease Control Rate)
timeFrame: 30 months
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers USOR
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Cancer
state: Florida
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Towson
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Omaha
country: United States
facility: XCancer/GU Research Network
state: Nebraska
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Oncology Hematology Consultants
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New YOrk
country: United States
facility: NYU Langone Health, Laura & Isaac Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Irving Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: UNC North Carolina Comprehensive Cancer Care Center
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists USOR
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates USOR
state: Virginia
city: Norton
country: United States
facility: Oncology and Hematology Associates Of Southwest Virginia USOR
state: Virginia
city: Madison
country: United States
facility: UW Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: NYU Langone Health
name: David Wise, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Mark Stein, MD
role: PRINCIPAL_INVESTIGATOR
References: