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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: ONC-392; Drug: lutetium Lu 177 vipivotide tetraxetan, IV infusion, Q6W for up to 6 doses.

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
• Enrollment (Estimated): 144
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Pan Zheng, MD, PhD; Phone Number: 105 8008829960; Email: pzheng@oncoc4.com

Study Locations

• United States
  • California
    • Davis, California, United States, 95817
      • Recruiting
      • University of California at Davis Cancer Center - 1624
      • Principal Investigator: Shuchi Gulati, MD
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Not yet recruiting
      • Rocky Mountain Cancer Center USOR - 1633
      • Principal Investigator: Allen Cohn, MD
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Not yet recruiting
      • Mount Sinai Cancer Research Program - 1619
      • Principal Investigator: Michael Cusnir, MD
    • Tampa, Florida, United States, 33612
      • Not yet recruiting
      • Moffitt Cancer Cancer- 1605
      • Principal Investigator: Monica chatwal, MD
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Not yet recruiting
      • Johns Hopkins University Medical Center - 1627
      • Principal Investigator: Channing Paller, MD
    • Towson, Maryland, United States, 21204
      • Recruiting
      • Chesapeake Urology Research Associates - 1609
      • Principal Investigator: Ronald Tutrone, MD
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Not yet recruiting
      • Lahey Hospital and Medical Center - 1626
      • Principal Investigator: Brendan Connell, MD
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Not yet recruiting
      • University of Mississippi Medical Center - 1618
      • Principal Investigator: Clark Henegan, MD
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • XCancer/GU Research Network - 1611
      • Principal Investigator: Luke Nordquist, MD, FACP
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute of New Jersey - 1614
      • Principal Investigator: Brian Saraiya, MD
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Not yet recruiting
      • New Mexico Hematology Oncology Assiciates - 1631
      • Principal Investigator: Jose Avitia, MD
  • New York
    • Buffalo, New York, United States, 14203
      • Not yet recruiting
      • Roswell Park Comprehensive Cancer Center - 1625
      • Principal Investigator: Gurkamal Chatta, MD
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health, Laura & Isaaac Perlmutter Cancer Center - 1601
      • Principal Investigator: David Wise, MD, PhD
    • New York, New York, United States, 13302
      • Recruiting
      • Columbia University Medical Center - 1602
      • Principal Investigator: Mark Stein, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Not yet recruiting
      • University of North Carolina Cancer Center - 1608
      • Principal Investigator: Young Whang, MD
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center - Duke Cancer Center - 1617
      • Principal Investigator: Andrew Armstrong, MD
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Not yet recruiting
      • The Ohio State University James Cancer Center - 1636
      • Principal Investigator: Lingbin Meng, MD
  • Oregon
    • Portland, Oregon, United States, 07239
      • Recruiting
      • Oregon Health and Science University Knight Cancer Institute - 1621
      • Principal Investigator: Alexandra Sokolova, MD
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center - 1604
      • Principal Investigator: Tian Zhang, MD
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Not yet recruiting
      • Virginia Cancer Specialists USOR - 1635
      • Principal Investigator: Alexander Spira, MD
    • Norfolk, Virginia, United States, 23502
      • Not yet recruiting
      • Virginia Oncology Associates USOR - 1616
      • Principal Investigator: Mark Fleming, MD
    • Norton, Virginia, United States, 24273
      • Not yet recruiting
      • Oncology Southwest Virginia USOR - 1634
      • Principal Investigator: David Buck, MD
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin Carbone Cancer Center (UWCCC) - 1612
      • Principal Investigator: Douglas McNeel, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult (≥ 18 years), capable of signing informed consent.
2. ECOG score 0 or 1. Life expectancy > 6 months. Adequate organ functions.
3. Histologically- or cytologically- confirmed diagnosis of metastatic prostate adenocarcinoma.
4. Patients must have a positive PSMA PET/CT scan.
5. 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).
6. Patients must have received at least one second generation AR-targeting agents (such as enzalutamide and/or abiraterone).

7. Patients must have been previously treated with at least 1, but no more than 2 previous taxane regimens. A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a patient has received only 1 taxane regimen, the patient is eligible if:

   1. The patient is not willing to receive a second taxane regimen, or
   2. The patient's physician deems him unsuitable to receive a second taxane regimen (e.g. frailty assessed by geriatric or health status evaluation or intolerance).

8. 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. Soft-tissue progression defined as an increase ≥20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions.
   3. Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (PCWG3 criteria).

Patients must have ≥1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging obtained ≤28 days prior to beginning study therapy.

Exclusion Criteria:

1. Patients who have not recovered to NCI CTCAE grade≤ 1 from an adverse event (AE) due to prior cancer therapeutics.
2. Receiving other anti-cancer agent or device, or participating in other clinical trial, within 28 days of first dose of study treatment.
3. 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.
4. 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.
5. Symptomatic brain metastasis, symptomatic cord compression, or clinical or radiological findings indicative of impending cord compression.
6. Active GI disease, including peptic ulcer disease, pancreatitis, diverticulitis, or inflammatory bowel disease.
7. Active infections.
8. Impaired heart function.
9. 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.
10. Diagnosed with other malignancies that having ant-cancer treatment within 2 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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 Names: Pluvicto
Active Comparator: lutetium Lu 177 vipivotide tetraxetan; lutetium Lu 177 vipivotide tetraxetan, IV infusion, Q6W for up to 6 doses.	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 Names: Pluvicto

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Objective response rate based on radiographic evaluation of PCWG3.	24 months
TEAE, TRAE and irAE	Incidence of TEAE, TRAE and irAE.	24 months

Collaborators and Investigators

• Sponsor: OncoC4, Inc.
• Collaborators: Prostate Cancer Clinical Trials Consortium
• Investigators: Principal Investigator: David Wise, MD, NYU Langone Health; Principal Investigator: Mark Stein, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: December 26, 2022
• First Submitted That Met QC Criteria: December 27, 2022
• First Posted (Actual): January 12, 2023

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
• Other Study ID Numbers: PRESERVE-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No