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

Metastatic Castration-resistant Prostate Cancer Clinical Trial

— PRESERVE-006  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05682443
• Other study ID #: PRESERVE-006
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 11, 2023
• Est. completion date: June 30, 2027

Study information

• Verified date: May 2024
• Source: OncoC4, Inc.
• Contact: Pan Zheng, MD, PhD
• Phone: 8008829960
• Email: pzheng[@]oncoc4.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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). Participants will be randomized to two arms 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 active control arm, they will be given standard of care treatment with lutetium Lu 177 vipivotide tetraxetan for up to 6 cycles.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• ONC-392
ONC-392 will be given as IV infusion, Q6W, for up to 9 doses.
• lutetium Lu 177 vipivotide tetraxetan, IV infusion, Q6W for up to 6 doses.
lutetium Lu 177 vipivotide tetraxetan will be given as IV infusion, Q6W, for up to 6 doses.

Locations

Country	Name	City	State
United States	New Mexico Hematology Oncology Assiciates - 1631	Albuquerque	New Mexico
United States	Rocky Mountain Cancer Center USOR - 1633	Aurora	Colorado
United States	Johns Hopkins University Medical Center - 1627	Baltimore	Maryland
United States	Roswell Park Comprehensive Cancer Center - 1625	Buffalo	New York
United States	Lahey Hospital and Medical Center - 1626	Burlington	Massachusetts
United States	University of North Carolina Cancer Center - 1608	Chapel Hill	North Carolina
United States	The Ohio State University James Cancer Center - 1636	Columbus	Ohio
United States	University of Texas Southwestern Medical Center - 1604	Dallas	Texas
United States	University of California at Davis Cancer Center - 1624	Davis	California
United States	Duke University Medical Center - Duke Cancer Center - 1617	Durham	North Carolina
United States	Virginia Cancer Specialists USOR - 1635	Fairfax	Virginia
United States	University of Mississippi Medical Center - 1618	Jackson	Mississippi
United States	University of Wisconsin Carbone Cancer Center (UWCCC) - 1612	Madison	Wisconsin
United States	Mount Sinai Cancer Research Program - 1619	Miami Beach	Florida
United States	Rutgers Cancer Institute of New Jersey - 1614	New Brunswick	New Jersey
United States	Columbia University Medical Center - 1602	New York	New York
United States	NYU Langone Health, Laura & Isaaac Perlmutter Cancer Center - 1601	New York	New York
United States	Virginia Oncology Associates USOR - 1616	Norfolk	Virginia
United States	Oncology Southwest Virginia USOR - 1634	Norton	Virginia
United States	XCancer/GU Research Network - 1611	Omaha	Nebraska
United States	Oregon Health and Science University Knight Cancer Institute - 1621	Portland	Oregon
United States	Moffitt Cancer Cancer- 1605	Tampa	Florida
United States	Chesapeake Urology Research Associates - 1609	Towson	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
OncoC4, Inc.	Prostate Cancer Clinical Trials Consortium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiographic progression free survival (rPFS)	• To assess the efficacy of ONC-392 plus lutetium Lu 177 vipivotide tetraxetan vs. lutetium Lu 177 vipivotide tetraxetan as assessed by radiographic progression free survival (rPFS). Disease progression was defined by PCWG3 guideline.	24 months
Secondary	Overall response rate (ORR)	Objective response rate based on radiographic evaluation of PCWG3.	24 months
Secondary	TEAE, TRAE and irAE	Incidence of TEAE, TRAE and irAE.	24 months