N-803 Alone or in Combination With BN-Brachyury Vaccine or Bintrafusp Alfa (M7824) for Participants With Castration Resistant Prostate Cancer

NCT05445882 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 10000309000309-C
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Prostate cancer does not trigger a strong immune response in the body. Hormone therapy, to reduce levels of testosterone in the body, can be helpful to treat some prostate cancers. However, castration-resistant prostate cancer (CRPC) keeps growing even when the testosterone is reduced to a very low level. Men with metastatic CRPC survive an average of only 3 years. More effective treatments are needed. Objective: To test whether an immunotherapy drug (N-803), alone or in combination with other drugs, can help treat CRPC. Eligibility: Males aged 18 or older with CRPC. Prior treatment with testosterone-lowering therapy is required. Design: Participants will be screened. They will have blood and urine tests. They will have a CT scan of the chest, abdomen, and pelvis. They will continue to receive hormone therapy for prostate cancer. Participants will come to the NIH clinic once a week for the first 4 weeks. Then they will come once every 2 weeks. Visits will last up to 8 hours. The study will continue up to 3 years. All participants will receive N-803 once every 2 weeks. The drug is injected just under the skin with a small needle. Some participants will receive N-803 plus another drug (brachyury vaccine). This drug is also injected under the skin with a small needle. Some participants will receive N-803 plus a different drug (bintrafusp alfa) once every 2 weeks. This drug is given through a tube attached to a needle placed in a vein in the arm. Some participants may receive all 3 drugs. Participants will have imaging scans every 12 weeks.

Conditions

Castration Resistant Prostate Cancer

Keywords

Pd-L1 Inhibitor; Il-15/ Il-15ra; Tgf-SS- Trap; Crpc

Outcome Measures

Primary Outcomes (1)

• Clinical Efficacy of N-803 alone or in combination with brachyury vaccine or bintrafusp alfa

  In each arm, the fraction who experience a response by 12 weeks will be noted and reported along with a 95% confidence interval.

  12 weeks

Secondary Outcomes (3)

• Duration of response

  3 years

• Radiographic response

  3 years

• Safety profile of N-803 alone or in combination with brachyury vaccine or bintrafusp alfa

  3 years

Study Arms (3)

Arm 1

EXPERIMENTAL

N-803 + BN-Brachyury (+ bintrafusp alfa if progression beyond 12 weeks)

Drug: N-803; Biological: BN-Brachyury

Arm 2

EXPERIMENTAL

N-803 (+ BN-Brachyury + bintrafusp alfa if progression beyond 12 weeks)

Drug: N-803

Arm 3

EXPERIMENTAL

N-803 + bintrafusp alfa (+ BN-Brachyury if progression beyond 12 weeks)

Drug: Bintrafusp alfa; Drug: N-803

Interventions

Bintrafusp alfa DRUG

Bintrafusp alfa (1,200 mg) will be given via IV infusion every 2 weeks for up to 3 years.

Arm 3

N-803 DRUG

N-803 (15 mcg/kg) subcutaneous injection will be given every 2 weeks for up to 3 years.

Arm 1; Arm 2; Arm 3

BN-Brachyury BIOLOGICAL

BN-Brachyury collectively refers to the priming doses (MVA-BN-Brachyury) and the boost doses (FPV-Brachyury). MVA-BN-Brachyury subcutaneous injection will be given as 2 priming doses 2 weeks apart. FPV-Brachyury subcutaneous injection will follow MVA-BN-Brachyury injection 2 weeks later every month for 6 months total, then every 3 months until reaching 2 years. After 2 years FPV-Brachyury may be continued at 6-month dosing intervals for up to 3 years.

Arm 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of castration-resistant prostate cancer (CRPC) with histologic confirmation of diagnosis at any time point prior to initiation of study therapy. Note: If a pathology report is unavailable, a history consistent with prostate cancer is sufficient.
• Prior treatment with testosterone lowering therapy for CRPC is required.
• Castrate testosterone level (\<50ng/dl or 1.7nmol /L).
• Radiological confirmation of metastatic disease
• Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:
• radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer
• PSA progression defined by sequence of rising values separated by \>1 week (2 separate increasing values over a minimum of 1 ng/ml (Prostate Cancer Working Group 3 (PCWG3) PSA eligibility criteria). If participants had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal. For participants on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal. The requirement for a 4-6-week withdrawal period following discontinuation of flutamide, nilutamide, or bicalutamide only applies to participants who have been on these drugs for at least the prior 6 months. For all other participants, they must stop bicalutamide, nilutamide, or flutamide prior to treatment initiation.
• Participants are willing to continue androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analog/antagonist or bilateral orchiectomy.
• Age \>=18 years.
• ECOG performance status \<= 1
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count \>= 1000/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9.0 g/dL
• Total bilirubin within normal institutional limits; in participants with Gilbert s, \<= 3.0 mg/dL

You may not qualify if:

• Participants who are immunocompromised as follows:
• Chronic administration (defined as daily or every other day for continued use \>14 days) of systemic corticosteroids or other immune suppressive drugs, within 28 days before treatment initiation. NOTE: Systemic corticosteroids at physiologic doses \<= 10 mg/day of prednisone or equivalent and steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are allowed. Nasal, or inhaled steroid, topical steroid creams, and eye drops for small body areas are also allowed.
• History of allogeneic peripheral stem cell transplantation, or solid organ transplantation requiring immunosuppression.
• Active autoimmune disease, except: participants with type 1 diabetes mellitus, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring current immunosuppression, or with other endocrine disorders on replacement hormones if the condition is well controlled.
• History of prostate cancer with brain/leptomeningeal metastasis. Note: Except if status post definitive radiotherapy or surgery and are asymptomatic.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents to be used.
• Known allergy to eggs, egg products, aminoglycoside antibiotics (e.g., gentamicin or tobramycin).
• Prior investigational drug, chemotherapy, immunotherapy, or any prior radiotherapy (except for palliative bone directed therapy) within the past 28 days prior to treatment initiation. Note: except if all treatment-related toxicities have resolved or are minimal and the participant meets all other eligibility criteria.
• Participants who have had cytotoxic chemotherapy for metastatic castration-resistant prostate cancer within the past year. NOTE: Participants who have had docetaxel for metastatic castration sensitive prostate cancer per CHAARTED data may enroll as long as they did not have progressive disease while on docetaxel and are 3 months removed from treatment, with all treatment-related toxicities resolving to at least grade 1.
• Uncontrolled intercurrent acute or chronic illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (\>New York Heart Association Class I), hepatic disease, unstable angina pectoris, serious cardiac arrhythmia, requiring medication, uncontrolled hypertension (SBP\>170/ DBP\>105) or psychiatric illness/social situations within 12 months before treatment initiation that would limit compliance with study requirements.
• History of bleeding diathesis or recent major bleeding events (i.e. Grade \>= 2 bleeding events within 4 weeks prior to study treatment initiation)
• Subjects unwilling to accept blood products or blood transfusions as medically indicated. As there is a risk of severe bleeding with M7824, participants must be willing to receive blood transfusions if medically necessary for their own safety
• Subjects who received a live vaccine within 4 weeks or COVID-19 vaccines within 2 weeks prior to the study treatment initiation.
• Use of herbal products that may decrease PSA levels (e.g., saw palmetto).
• Major surgery within 4 weeks before treatment initiation. NOTE: A biopsy will not preclude a subject from starting the study.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

bintrafusp alfa protein, human; ALT-803

Study Officials

• James L Gulley, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 2, 2022
• First Posted: July 6, 2022
• Study Start: April 1, 2024
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: April 2, 2024

Record last verified: 2021-04

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 database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)