A Phase II Study Evaluating T-Cell Clonality After Stereotactic Body Radiation Therapy Alone and in Combination With the Immunocytokine PDS01ADC in Localized High and Intermediate Risk Prostate Cancer Treated With Androgen Deprivation Therapy

NCT05361798 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10000114000114-C
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Prostate cancer is often treated with radiation and ADT (ADT is androgen deprivation therapy). Up to 30% of these cancers recur within 5 years of treatment. Researchers want to see if a new drug (PDS01ADC) can help the immune system to fight prostate cancer. Objective: To find what doses of PDS01ADC are safe in people who are treated for prostate cancer. Also, to see what effects PDS01ADC has on the immune system. Eligibility: People aged 18 and older with high- and intermediate-risk prostate cancer. Their cancer must not have spread to other parts of the body. Design: The study will last 7 months. Participants will be screened. They will share their medical history. They will also have: \<TAB\>A physical exam \<TAB\>Routine blood and urine tests \<TAB\>Imaging scans of the chest, abdomen, and pelvis \<TAB\>A bone scan \<TAB\>A tumor biopsy \<TAB\>A specialized MRI. Participants will lie face down on the MRI scanner table. An antenna that receives a signal may be placed in the rectum. All participants will be treated with radiation therapy and ADT. Some participants will also receive PDS01ADC as an injection under the skin. This treatment will start 4 weeks after the radiation has ended. Participants will receive a total of 3 doses. The injections will be 4 weeks apart. Some screening tests will be repeated at each visit. Participants who do not receive PDS01ADC will also have screening tests during the treatment period. Participants will return for follow-up about 1 month after the last treatment or set of tests.

Conditions

Cancer Of Prostate

Keywords

Immunotherapy + Radiation; Combination Therapy; Cancer Of Prostate; Nhs-Il 12

Outcome Measures

Primary Outcomes (2)

• To determine safety and tolerated doses of PDS01ADC and SBRT

  For the safety lead-in: grade and type of toxicities at each dose level will be assessed to determine safety and tolerated doses of PDS01ADC in combination with SBRT in participants with high and intermediate risk prostate cancer receiving standard of care ADT

  four weeks after start of treatment

• evaluate T-cell clonality as measures of immunologic activity

  Relative T-cell antigen receptor (TCR) clonality for each participant will be formed and these ratios will be compared between the two arms.

  baseline through 4 weeks after end of treatment

Secondary Outcomes (1)

• Evaluate peripheral immune response

  baseline through 4 weeks after end of treatment

Study Arms (3)

1/Arm 1

EXPERIMENTAL

De-escalating doses of PDS01ADC if appropriate + SBRT

Drug: PDS01ADC; Radiation: Stereotactic Body Radiation Therapy (SBRT)

2/Arm 2a

EXPERIMENTAL

Highest tolerated dose of PDS01ADC+SBRT

Drug: PDS01ADC; Radiation: Stereotactic Body Radiation Therapy (SBRT)

3/Arm 2b

EXPERIMENTAL

SBRT

Radiation: Stereotactic Body Radiation Therapy (SBRT)

Interventions

Stereotactic Body Radiation Therapy (SBRT) RADIATION

SBRT to the prostate will be delivered in 5 fractions of radiation each of 7.25-8.0 Gy, every other day over the course of 10 business days (2-3 weeks). The total dose will be 36.25-40 Gy

1/Arm 1; 2/Arm 2a; 3/Arm 2b

PDS01ADC DRUG

In the safety lead in, PDS01ADC will be given in de-escalating doses (starting dose 16.8 mcg/kg, and de-escalated if needed to 12 mcg/kg, or 8 mcg/kg) every 4 weeks for 3 doses. Within 4 weeks after completing SBRT, those participants receiving immunotherapy agents will receive M9241 by subcutaneous injection at dose determined during the safety lead in every 4 weeks for 3 doses.

1/Arm 1; 2/Arm 2a

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed localized intermediate or high risk prostate cancer:
• Intermediate risk - Gleason 7 disease, PSA less than 10
• High Risk - Gleason 8-10, PSA\>10, Extracapsular Extension
• Participants must require treatment with SBRT to the prostate and ADT.
• Pre-treatment tissue availability (collected \<= 1 year to initiation of study therapy) for biomarker analysis is mandatory for enrollment. If tissue is determined to be of insufficient/unsuitable quality/quantity, a pre-treatment biopsy prior to initiation of study therapy will be required.
• Male age \>= 18 years old
• ECOG performance status \< 2
• Participants must have adequate organ and marrow function as defined below:
• absolute neutrophil count \>= 1,500/mcL, without CSF support
• platelets \>= 100,000/mcL
• AST(SGOT)/ALT(SGPT) \<= 2.5 X institutional upper limit of normal
• Hgb \>= 10g/dL (pRBC transfusions are not allowed to achieve acceptable Hgb)
• Total bilirubin \<= 1.5 x upper limit of normal (ULN),
• in participants with Gilbert s syndrome, a total bilirubin \<= 3.0
• Serum albumin \>= 2.8 g/dL

You may not qualify if:

• Evidence of distant metastatic disease (including clinically or pathologically positive lymph nodes or metastatic disease outside of the pelvis).
• Previous prostatectomy, focal therapy, or radiation to the prostate. Note: Previous finasteride, dutasteride, bicalutamide are allowed at PI discretion.
• Initiation of ADT or SBRT or pelvic nodal radiation irradiation prior to trial enrollment (no time limit).
• Live vaccine therapies for the prevention of infectious disease within 30 days prior to treatment administration. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID vaccines are permitted.
• Contraindication to mpMRI including allergy or sensitivity to contrast agents (which cannot be alleviated by premedication)
• Contraindications for SBRT such as: rectal wall invasion, history of inflammatory bowel disease, prior radiation in the treatment field that would exceed tissue tolerance.
• Medical comorbidities that preclude the administration of androgen deprivation therapy or uncontrolled chronic or acute intercurrent illness /social situations or other illnesses considered by the Investigator as high risk for investigational drug treatment
• Participants with active immune deficiencies, chronic inflammatory conditions, active autoimmune diseases, or participants on chronic immunosuppressive therapy for whom the primary endpoint of immune response could be impacted.
• Participants requiring requiring systemic corticosteroids (\>10 mg daily prednisone equivalent) or immunosuppressive medications except inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or dose not threaten vital organ function including CN, heart, lungs, kidneys, skin and GI track will be allowed
• Participants with HIV
• Active Hepatitis B or Hepatitis C infection
• Significant acute or chronic infections including tuberculosis (history of exposure or history of positive tuberculosis test; plus, presence of clinical symptoms, physical or radiographic findings)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to PDS01ADC.
• Participants with prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast or low risk Gleason 6 prostate cancer.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Melissa L Abel, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy R Hankin, P.A.-C

CONTACT

(240) 858-3149; amy.hankin@nih.gov

Melissa L Abel, M.D.

CONTACT

(240) 447-5353; melissa.abel@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2022
• First Posted: May 5, 2022
• Study Start: June 12, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as the database is active
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.

Locations

US (1)