Sipuleucel-T (Sip-T) in Combination With N-803 in Metastatic Androgen Pathway Modulation Resistant (mAPMR) Prostate Cancer

NCT07756593 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 26-x147
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib single-center open-label de-escalation study uses a modified 3+3 design to determine the safety, tolerability, and recommended phase II dose (RP2D) of the combination of standard of care Sip-T and N-803 in patients with metastatic androgen pathway modulation resistant (mAPMR) prostate cancer. Patients will receive treatment for up to 8 weeks.

Conditions

Prostate Cancer; Metastatic Prostate Cancer

Keywords

Prostate Cancer; Immunotherapy; Sipuleucel-T; IL-15; Metastatic Prostate Cancer; Cellular Therapy; Cytokine Therapy; Combination Trial

Outcome Measures

Primary Outcomes (4)

• Frequency of dose-limiting toxicities (Cohort 1 only)

  As assessed via CTCAE v6.0. Dose limiting toxicities will be evaluated according to protocol.

  Start of treatment (day 1 dose of Sip-T) through 14 days following the last dose of N-803 (total time up to 44 days)

• Recommended Phase II Dose (RP2D) (Cohort 1 only)

  RP2D is defined as the highest dose of N-803 that has an overall DLT rate of less than 33% in total of 6 patients.

  Start of treatment (day 1 dose of Sip-T) through 14 days following the last dose of N-803 for all participants in Cohort 1 (total time up to 44 days)

• Number of severe (grade 3+) adverse events measured via CTCAE v6.0

  Start of treatment through 100 days after last dose of N-803 (total time up to 137 days)

• Number and type of adverse events measured via CTCAE v6.0

  Start of treatment through 100 days after last dose of N-803 (total time up to 137 days)

Secondary Outcomes (7)

• PSA30 Response

  Start of treatment to completion of follow-up (up to 26 months)

• PSA50 Response

  Start of treatment to completion of follow-up (up to 26 months)

• PSA90 Response

  Start of treatment to completion of follow-up (up to 26 months)

• Radiographic progression-free survival (PFS)

  Start of treatment to date of progression or death or last follow-up (up to 26 months)

• Failure-free survival (FFS)

  Start of treatment to date of any progression events or last follow-up (up to 26 months)

Study Arms (5)

Cohort 1: Dose level 0 Starting dose: N-803 + SIP-T

EXPERIMENTAL

Patients will receive standard dose (\>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 15 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30.

Biological: Sipuleucel-T; Biological: N803

Cohort 1: Dose level -1: N-803 + SIP-T

EXPERIMENTAL

Patients will receive standard dose (\>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 10 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30.

Biological: Sipuleucel-T; Biological: N803

Cohort 1: Dose level -2: N-803 + SIP-T

EXPERIMENTAL

Patients will receive standard dose (\>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and 6 mcg/kg SC dose of N-803 24 hours after SIP-T on Day 2, 16, and 30.

Biological: Sipuleucel-T; Biological: N803

Cohort 2: N-803 + SIP-T

EXPERIMENTAL

Patients will receive standard dose (\>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and recommended phase 2 dose (RP2D) of N-803 24 hours after SIP-T on Day 2, 16, and 30. An additional dose of N-803 will occur on Day -5 or 5 days before first SIP-T dose.

Biological: Sipuleucel-T; Biological: N803

Cohort 3: N-803 + SIP-T

EXPERIMENTAL

Patients will receive standard dose (\>50 million CD54+ cells) subcutaneous (SC) SIP-T on Day 1, 15 and 29 and RP2D of N-803 24 hours after SIP-T on Day 2, 16, and 30. An additional dose of N-803 will occur on Day 37.

Biological: Sipuleucel-T; Biological: N803

Interventions

Sipuleucel-T BIOLOGICAL

Sipuleucel-T is a cellular therapeutic vaccine given in 3 complete doses at 2-week intervals intravenously.

Also known as: Provenge, SipT

Cohort 1: Dose level -1: N-803 + SIP-T; Cohort 1: Dose level -2: N-803 + SIP-T; Cohort 1: Dose level 0 Starting dose: N-803 + SIP-T; Cohort 2: N-803 + SIP-T; Cohort 3: N-803 + SIP-T

N803 BIOLOGICAL

N-803 is a biologic that is administered subcutaneously in the abdominal area.

Cohort 1: Dose level -1: N-803 + SIP-T; Cohort 1: Dose level -2: N-803 + SIP-T; Cohort 1: Dose level 0 Starting dose: N-803 + SIP-T; Cohort 2: N-803 + SIP-T; Cohort 3: N-803 + SIP-T

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed prostate adenocarcinoma.
• Imaging- or biopsy-proven metastatic disease. May have any type or location of metastases (bone, lymph node, visceral).
• Prior treatment must include either orchiectomy or luteinizing hormone-releasing agonist or antagonist treatment with documented testosterone ≤ 50 ng/dL.
• Eligible for standard of care Sipuleucel-T.
• Recovery to baseline or ≤ grade 1 from toxicities related to any prior treatments, unless AEs are clinically nonsignificant and/or stable on supportive therapy.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Adequate bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,500 K/cumm without granulocyte colony-stimulating factor support
• Platelets ≥ 100,000 K/cumm without transfusion
• Hemoglobin ≥ 10.0 g/dL
• Total bilirubin ≤ 1.5 x IULN
• AST(SGOT) and ALT(SGPT) ≤ 2.5 x IULN
• Calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault
• PSA ≤ 200 ng/mL.

You may not qualify if:

• Rapidly progressing disease or symptomatic prostate cancer as assessed by the investigator.
• Prior immunotherapy (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) within the 6 months prior to enrollment.
• Prior systemic radiotherapy (such as Ra-223, Lu177-PSMA) within the 6 months prior to enrollment. Prior palliative radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment is allowed. Prior definitive radiation therapy for localized prostate cancer is allowed.
• Prior exposure to Sipuleucel-T.
• Ongoing systemic immune suppression (oral steroids equivalent to 10 mg daily prednisone or less are allowed; topical, inhaled, and intra-articular steroids are allowed).
• Currently receiving any other investigational therapeutic or imaging agents.
• Patients with known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to Sipuleucel-T or N-803 or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Function Classification; to be eligible for this trial, patients should be a class 2B or better.
• HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
• Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
• History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.
• Uncontrolled infection with hepatitis A.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Dendreon: collaborator
• ImmunityBio, Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

sipuleucel-T; ALT-803

Condition Hierarchy (Ancestors)

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

Study Officials

• Russell K Pachynski, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Russell K Pachynski, M.D.

CONTACT

314-286-2341; rkpachynski@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: August 10, 2026
• Study Start (Estimated): November 30, 2026
• Primary Completion (Estimated): April 14, 2029
• Study Completion (Estimated): January 31, 2031
• Last Updated: August 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be made available beginning 9 months and ending 36 months following publication.
• Access Criteria: Investigators who have approval to use the data by an independent review committee.

Locations

US (1)