ONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With mCRPC (PRESERVE-006)

• ClinicalTrials.gov Identifier: NCT05682443
• Recruitment Status: Recruiting
• First Posted: January 12, 2023
• Last Update Posted: May 10, 2024
• Sponsor: OncoC4, Inc.
• Collaborator: Prostate Cancer Clinical Trials Consortium
• Information provided by (Responsible Party): OncoC4, Inc.

Tracking Information

• First Submitted Date: December 26, 2022
• First Posted Date: January 12, 2023
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: December 11, 2023
• Estimated Primary Completion Date: June 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 27, 2022)

Radiographic progression free survival (rPFS) [ Time Frame: 24 months ]

• 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 27, 2022)

• Overall response rate (ORR) [ Time Frame: 24 months ]
  Objective response rate based on radiographic evaluation of PCWG3.
• TEAE, TRAE and irAE [ Time Frame: 24 months ]
  Incidence of TEAE, TRAE and irAE.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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).

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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized, open label, active controlled, multi-center study

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Metastatic Castration-resistant Prostate Cancer

Intervention

• Drug: ONC-392
  ONC-392 will be given as IV infusion, Q6W, for up to 9 doses.
  Other Names:

  • A humanized anti-CTLA4 IgG1 monoclonal antibody
  • Gotistobart
• Drug: 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.
  Other Name: Pluvicto

Study Arms

• Experimental: Arm A: ONC-392 plus lutetium Lu 177 vipivotide tetraxetan
  Arm A receives ONC-392, IV infusion, for up to 9 doses, plus lutetium Lu 177 vipivotide tetraxetan IV infusion, Q6W for up to 6 doses.
  Interventions:

  • Drug: ONC-392
  • Drug: lutetium Lu 177 vipivotide tetraxetan, IV infusion, Q6W for up to 6 doses.
• Active Comparator: lutetium Lu 177 vipivotide tetraxetan
  lutetium Lu 177 vipivotide tetraxetan, IV infusion, Q6W for up to 6 doses.
  Intervention: Drug: lutetium Lu 177 vipivotide tetraxetan, IV infusion, Q6W for up to 6 doses.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 9, 2023): 144
• Original Estimated Enrollment (submitted: December 27, 2022): 90
• Estimated Study Completion Date: June 30, 2027
• Estimated Primary Completion Date: June 30, 2026 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pan Zheng, MD, PhD; 8008829960 ext 105; pzheng@oncoc4.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05682443
• Other Study ID Numbers: PRESERVE-006
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: OncoC4, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: OncoC4, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Prostate Cancer Clinical Trials Consortium

Investigators

• Principal Investigator: David Wise, MD; NYU Langone Health
• Principal Investigator: Mark Stein, MD; Columbia University

• PRS Account: OncoC4, Inc.
• Verification Date: May 2024