A Phase I/II Study of PDS01ADC With Docetaxel and Abiraterone in Adults With Metastatic Castration Sensitive and PDS01ADC With Docetaxel in Castration Resistant Prostate Cancer

NCT04633252 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 21000121-C-0001
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Metastatic castration sensitive and castration resistant prostate cancer (mCSPC and mCRPC) are prostate cancers that have spread to other parts of the body. Use of the drug docetaxel with androgen deprivation therapy can improve survival for men with mCSPC. Researchers want to see if combining this treatment with other drugs can help delay the time it takes for mCSPC and mCRPC to get worse. Objective: To learn if giving docetaxel with PDS01ADC is safe and effective for men with prostate cancer. Eligibility: Men age 18 and older with mCSPC or mCRPC. Design: Participants will be screened with a medical history and physical exam. Their diagnosis will be confirmed. Their symptoms and how well they do their normal activities will be reviewed. They will have blood and urine tests. Their heart will be evaluated. They will have imaging scans of the chest, abdomen, and pelvis. They will have bone scans with intravenous (IV) injections of Tc99 to check for tumor spread in the bones. Some screening tests will be repeated during the study. Participants may have tumor biopsies. Participants will get treatment in cycles. Each cycle will last 21 days. They will get docetaxel through IV infusion. They will get PDS01ADC as an injection under the skin. Participants with mCSPC will have up to 6 cycles. Those with mCRPC will be treated until they cannot tolerate the side effects or their disease gets worse. Participants will have a follow-up visit 30 days after treatment ends. Those with mCSPC will then have follow-up visits at the clinic every 3 months.

Conditions

Cancer Of Prostate; Prostate Neoplasms

Keywords

Chemoimmunotherapy; NHS IL-12; Check point inhibitor; Combination Therapy

Outcome Measures

Primary Outcomes (2)

• Determine clinical efficacy in adults with prostate cancer treated with docetaxel in combination with the immunocytokine, PDS01ADC

  For castration sensitive: Increase in the proportion of participants who have less than 0.2 ng/ml of PSA. For castration resistant: Increase in median progression free survival

  4-8 weeks

• To evaluate safety and tolerability of docetaxel in combination with PDS01ADC in patients who have metastatic prostate cancer.

  of the number and type of toxicities noted for participants who are evaluable for toxicity

  DLT observation period (until the end of 6 weeks)

Secondary Outcomes (3)

• Evaluate radiographic response rates

  4-8 weeks

• Evaluate percentage of patients with a 50% PSA decline from baseline

  4-8 weeks

• Evaluate radiographic and biochemical time to progression for mCSPC patients

  7 months

Study Arms (4)

1/Dose Escalation

EXPERIMENTAL

Docetaxel plus PDS01ADC dose escalation with optional prednisone and ADT as part of SOC

Drug: PDS01ADC; Drug: Docetaxel; Drug: Prednisone; Drug: ADT

2/Safety Run-in (no longer applies; removed before enrollment)

EXPERIMENTAL

Docetaxel plus PDS01ADC RP2D plus M7824 with optional prednisone and ADT as part of SOC

Drug: PDS01ADC; Drug: Docetaxel; Drug: M7824; Drug: Prednisone; Drug: ADT

3/mCSPC: Dose Expansion

EXPERIMENTAL

Docetaxel plus PDS01ADC RP2D with optional prednisone and ADT as part of SOC

Drug: PDS01ADC; Drug: Docetaxel; Drug: Prednisone; Drug: ADT

4/mCRPC: Dose Expansion

EXPERIMENTAL

Docetaxel plus PDS01ADC RP2D with optional prednisone and ADT as part of SOC

Drug: PDS01ADC; Drug: Docetaxel; Drug: Prednisone; Drug: ADT

Interventions

ADT DRUG

For mCSPC patients: Androgen Deprivation Therapy (ADT) may include GnRH agonist or monthly degarelix converted to GnRH agonist after 3 months. For mCRPC patients: ADT will be continued as per standard of care.

1/Dose Escalation; 2/Safety Run-in (no longer applies; removed before enrollment); 3/mCSPC: Dose Expansion; 4/mCRPC: Dose Expansion

Prednisone DRUG

For mCSPC patients, prednisone is optional and if given, should be taken orally, at 5 mg once a day. For mCRPC patients, prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day as is the patient s preference.

1/Dose Escalation; 2/Safety Run-in (no longer applies; removed before enrollment); 3/mCSPC: Dose Expansion; 4/mCRPC: Dose Expansion

M7824 DRUG

M7824 (2400 mg) will be administered as a 1 hour intravenous (IV) infusion once every three weeks.

2/Safety Run-in (no longer applies; removed before enrollment)

Docetaxel DRUG

Docetaxel 75mg/m\^2 will be administered intravenously every 21 days (i.e., a 3-week cycle) for up to 6 cycles in mCSPC and until progression or unacceptable toxicity in mCRPC.

1/Dose Escalation; 2/Safety Run-in (no longer applies; removed before enrollment); 3/mCSPC: Dose Expansion; 4/mCRPC: Dose Expansion

PDS01ADC DRUG

PDS01ADC at escalating doses and then at RP2D will be administered as a subcutaneous injection every three weeks.

1/Dose Escalation; 2/Safety Run-in (no longer applies; removed before enrollment); 3/mCSPC: Dose Expansion; 4/mCRPC: Dose Expansion

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have documented histopathological confirmation of prostate cancer. If no pathologic specimen is available, participants may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
• Participants must have metastatic disease, defined as at least one lesion on TC99 bone scan or at least one lesion that is measurable per, per RECIST 1.1.
• mCSPC participants:
• Participants must be within 134 days of starting ADT.
• If participants are on ADT and responding, this may impact the findings on scans. Pre- treatment scans could be used to confirm that participants have metastatic high-volume disease in such cases.
• For Cohorts 1 and 2, Dose escalation and Safety Run-in, only: mCSPC may have high or low volume disease.
• For Cohort 3, Dose Expansion: mCSPC participants must have high volume disease (as defined by visceral lesion or 4 or greater bone lesions, at least one of which is beyond the spine and pelvis).
• mCRPC participants:
• Must need ADT as part of their cancer therapy (unless previous orchiectomy)
• Must have been previously treated with modern anti-androgens such as abiraterone, enzalutamide, apalutamide, or darolutamide.
• Must have not had progression while on docetaxel if given for mCSPC or within 3 months of completing docetaxel for mCSPC.
• Progression defined as either rising PSA greater than 2.0 ng/ml or radiographic evidence of progression seen on CT scan or TC-99 bone scan.
• Toxicities related to prior therapy, including surgery and/ or radiation, must have resolved to \<= grade 1.
• Participants must have documented histopathological confirmation of prostate cancer. If no pathologic specimen is available, participants may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
• Participants must have metastatic disease, defined as at least one lesion on TC99 bone scan or at least one lesion that is measurable per, per RECIST 1.1.

You may not qualify if:

• Immunocompromised status due to:
• Human immunodeficiency virus (HIV) positivity
• Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including CNS, heart, lungs, kidneys, skin, and GI tract will be allowed.
• Other immunodeficiency diseases that in the opinion of the investigator could compromise the participant or limit treatment efficacy
• Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with participant s ability to carry out the treatment program.
• Current use of other medications for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
• Concurrent use of CYP3A4 inducers or sensitive CYP2D6 substrates within 14 days or 5 half-lives, whichever is shorter.
• Receipt of any investigational agent within 28 days (or 60 days for an antibody drug conjugates) before the first planned dose of study drugs.
• Participants who are positive for Hepatitis B surface antigen and/or Anti-Hepatitis C antibody
• Uncontrolled hypertension (SBP\>170/ DBP\>105)
• Has received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID vaccines are permitted.
• Participants who have had prior docetaxel for mCRPC
• mCSPC participants will be excluded if they did not start abiraterone within 6 weeks of ADT and/or had any docetaxel
• Participants who have had progression within 3 months of completing docetaxel for mCSPC
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to PDS01ADC investigational agents used in the study

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

Docetaxel; Prednisone

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

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 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: November 18, 2020
• Study Start: February 23, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-03-23

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)