Enzalutamide and PDS01ADC in PET Positive Recurrent Prostate Cancer (pprPC) Without Testosterone Lowering Therapy

Last updated: May 21, 2025
Sponsor: National Cancer Institute (NCI)
Overall Status: Active - Recruiting

Phase

2

Condition

Prostate Cancer

Prostate Disorders

Urologic Cancer

Treatment

M9241

Enzalutamide

PDS01ADC

Clinical Study ID

NCT06096870
10001556
001556-C
  • Ages 18-120
  • Male

Study Summary

Background:

Prostate cancer may return after treatment in 30,000 to 50,000 people each year. There is no clear best way to treat these people. Better treatments are needed.

Objective:

To test a study drug (enzalutamide), both alone and combined with a second drug (PDS01ADC), in people with prostate cancer that returned after treatment.

Eligibility:

People aged 18 years and older with prostate cancer that returned after treatment.

Design:

Participants will be screened. They will have a physical exam, with blood tests. All their urine will be collected for 24 hours. They will have imaging scans of their chest, abdomen, pelvis, and bones. Their ability to perform everyday activities will be assessed. They may opt to give a stool sample.

Participants will be treated in 4-week cycles.

Enzalutamide is a pill taken by mouth once a day, every day. All participants will be given a supply of this drug to take at home.

PDS01ADC is injected under the skin once a month, on the first day of each cycle. Half of the participants will receive both drugs.

All participants will visit the clinic once a month. Each visit should last no more than 8 hours. Blood and urine tests will be repeated.

All participants will receive the study treatment for 3 cycles. Some participants may need 3 more cycles of treatment with enzalutamide only. This re-treatment can be done only once.

Participants will have a follow-up visit 1 month after they finish treatment. After that, they will have visits every 6 weeks for up to 5 years. Imaging scans and blood tests will be repeated.

...

Eligibility Criteria

Inclusion

  • INCLUSION CRITERIA:

  • Participant must provide documentation of histologic or cytological confirmation ofprostate cancer or tumor sample for diagnosis confirmation. Note: in the absence ofpathology or documentation, participant must have a rising PSA, PSMA+ disease, andhis history consistent with prostate cancer as documented by the investigator.

  • History of primary treatment for prostate cancer (either surgery or radiation).

  • Prostate-specific antigen (PSA) doubling time within less than 12 months.

  • Testosterone >100 ng/dL.

  • Age >=18 years.

  • Evidence of prostate cancer on PSMA PET/CT scan.

  • Eastern Cooperative Oncology Group (ECOG) performance status <2.

  • Men must agree to use an effective method of contraception (barrier or surgicalsterilization) after study entry and for 3 months after completion of enzalutamideor PDS01ADC therapy whatever comes later.

  • Participants must have adequate organ and marrow function as defined below:

  • Absolute neutrophil count (ANC) >=1,500/microliter, without granulocytecolony-stimulating factor (G-CSF) support

  • Platelets >=100,000/microliter

  • Aspartate aminotransferase (AST) /Alanine aminotransferase (ALT) <=2.5 xinstitutional upper limit of normal (ULN)

  • Hemoglobin (Hgb) >= 10 g/dL (packed red blood cell (pRBC) transfusions are notallowed to achieve acceptable Hgb)

  • Total bilirubin <= 1.5 x ULN, OR <= 3.0 ULN in participants with Gilbert ssyndrome

  • Serum albumin >= 2.8 g/dL

  • Creatinine < 1.5 X institution ULN

OR

--Measured or calculated creatinine clearance (CrCl) (estimated glomerular filtration rate (eGFR) may also be used in place of CrCl) > 45 mL/min/1.73 m^2 for participant with creatinine levels > 1.5 x institutional ULN

  • Hepatitis B virus (HBV)-infected participants can be enrolled if HBV DNA isundetectable at screening. Hepatitis C virus (HCV)-infected participants can beenrolled if the HCV RNA level is undetectable at screening. Human immunodeficiencyvirus (HIV)-positive participants can be enrolled if HIV DNA is undetectable.

  • Participants must be able to swallow tablets/capsules.

  • Participants must be able to understand and willing to sign a written informedconsent document.

Exclusion

EXCLUSION CRITERIA:

  • Evidence of soft tissue disease on CT scan (or magnetic resonance imaging (MRI) ifassessment cannot be done by CT scan) per RECIST 1.1 criteria (lymph nodes up to 2.0cm in the shortest dimension are allowed).

  • Evidence of bone lesions on Tc99 bone scan.

  • History of allergic reactions attributed to compounds of similar chemical orbiologic composition to study drugs or imaging agents used in the study.

  • Any medical condition that requires chronic systemic steroid therapy, or any otherform of immunosuppressive medication (inhaled and topical steroids are permitted).

  • History of seizures within the last 10 years.

  • Therapy with strong inhibitors or inducers of CYP2C8 or CYP3A4 (https://druginteractions.medicine.iu.edu/MainTable.aspx) within 5 half-lives priorto the study treatment initiation.

  • Participants with prior malignancy active within 3 years prior to study treatmentinitiation except for locally curable cancers that have been apparently cured suchas basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma insitu of the breast.

  • Uncontrolled intercurrent illness that would limit compliance with studyrequirements.

Study Design

Total Participants: 65
Treatment Group(s): 3
Primary Treatment: M9241
Phase: 2
Study Start date:
April 22, 2024
Estimated Completion Date:
December 31, 2029

Study Description

  • Enzalutamide given with androgen deprivation therapy (ADT) is Food and Drug Administration (FDA) approved for the treatment of metastatic prostate cancer based on conventional computed tomography (CT) and Tc99 scan.

  • Enzalutamide for 3 months (short course) given without ADT has demonstrated the ability to control prostate-specific antigen (PSA) in recurrent prostate cancer for nearly a year, delaying the need for additional therapy.

  • Enzalutamide without ADT was very well tolerated in our previous study, a prerequisite for any therapy in recurrent disease where patients may not have symptoms from prostate cancer for 5-10 years.

  • Enzalutamide without ADT demonstrated the ability to enhance natural killer (NK) cells and decrease myeloid-derived suppressor cells.

  • PDS01ADC is an immunocytokine that binds to areas of necrotic tumors. Preclinical data have demonstrated that PDS01ADC delivery to the tumor is enhanced by cytotoxic therapies such as radiation and chemotherapy.

  • PDS01ADC has been shown to be well tolerated and even induce PSA responses in patients with recurrent prostate cancer.

  • PDS01ADC has also been able to enhance NK cells in prostate cancer patients.

  • Higher levels of NK cells have been associated with better clinical outcomes in prostate cancer.

  • Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging is now approved in recurrent prostate cancer. No trial has prospectively evaluated an anti-androgen therapy (e.g., enzalutamide) without ADT in this population. If changes in imaging are seen similar to the PSA responses noted previously, these findings may demonstrate the efficacy of enzalutamide-based regimens in recurrent prostate cancer.

  • Given that enzalutamide is cytotoxic and will induce necrosis, there is a rationale to combine it with the necrosis-targeting agent PDS01ADC. The fact that both enhance NK cells, which have been associated with better clinical outcomes adds further rationale to this combination.

Objective:

-To determine if the combination of enzalutamide and immunotherapy (PDS01ADC) is associated with an increase in the duration of PSA suppression compared to that of enzalutamide alone in participants with PET Positive Recurrent Prostate Cancer (pprPC).

Eligibility:

  • Participant must provide documentation of histologic or cytological confirmation of prostate cancer or tumor sample for diagnosis confirmation. Note: in the absence of pathology or documentation, participant must have a rising PSA, PSMA plus disease, and his history consistent with prostate cancer as documented by the investigator.

  • History of primary treatment for prostate cancer (either surgery or radiation).

  • PSA doubling time within less than 1 year before treatment initiation.

  • Testosterone >100 ng/dL.

  • Age >=18 years.

  • Evidence of prostate cancer on PSMA PET/CT scan.

  • Negative Tc99 Bone Scan.

  • No evidence of soft tissue disease on the CT scan (or MRI) per the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).

Design:

  • This is an open-label phase II clinical trial with two treatment arms: Arm 1 (enzalutamide) and Arm 2 (enzalutamide plus PDS01ADC).

  • After enrollment, participants will be randomized between Arms 1 and 2 and receive 3 cycles of treatment of enzalutamide or enzalutamide and PDS01ADC.

  • During off treatment monitoring period following the third cycle, participants who experience PSA recovery to baseline will have a second course of enzalutamide treatment only (3 cycles total).

Connect with a study center

  • National Institutes of Health Clinical Center

    Bethesda, Maryland 20892
    United States

    Active - Recruiting

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