Phase I/II Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, N-803 and Epacadostat (QuEST1)

Summary

Background:

Immunotherapy drugs help the body to fight cancer. Scientists think that combining some of these drugs will make them work better than when used alone. This may be true for many types of cancer, including castration-resistant prostate cancer (CRPC).

Objective:

To test if any of the combinations of drugs below have anti-prostate cancer activity and to test if they are safe.

1. Bavarian-Nordic (BN)-brachyury, bintrafusp alfa (M7824).
2. Bavarian-Nordic (BN)-brachyury, bintrafusp alfa (M7824) + Anktiva (N-803).
3. Bavarian-Nordic (BN)-brachyury, bintrafusp alfa (M7824) + Anktiva (N-803) + Epacadostat.

Eligibility:

People ages 18 and older with CRPC or another metastatic cancer

Design:

Participants will be screened with:

* Medical history
* Physical exam
* Computed tomography (CT) or magnetic resonance imaging (MRI) scans
* Possible bone imaging
* Blood, urine, and heart tests
* Possible tumor biopsy

Participants will be treated with a 2-, 3- or 4-drug combinations of the following study drugs in 2-week cycles:

* Participants will receive M7824 by intravenous (IV) once every 2 weeks.
* Participants will receive N-803 by injection once every 2 weeks. They will record any skin changes at the injection site in a diary.
* Participants will receive BN-brachyury as 4 injections to different limbs. They will get the first 3 doses 2 weeks apart. Then they will get doses every 4 weeks for 6 months, then every 3 months for 2 years, then every 6 months.
* Participants will take Epacadostat orally every 12 hours. They will keep a pill diary.

Participants will have physical exams and blood and urine tests at the start of each cycle. They may have scans every 12 weeks.

Participants will continue treatment until their disease gets worse or they cannot tolerate the side effects.

Participants will have a follow-up visit 4-5 weeks after they stop treatment. They will have a physical exam and blood tests. They may be asked to return for scans every 3 months.

Conditions

• Metastatic Castration-resistant Prostate Cancer
• Prostate Cancer
• Prostate Neoplasm
• Advanced Solid Tumor
• Solid Tumor
• Non-metastatic Castration-resistant Prostate Cancer

Interventions

BIOLOGICAL

M7824

1,200 mg intravenous (IV) once every 2 weeks.

DRUG

N-803

8-15 mcg/kg subcutaneous every 2 weeks.

BIOLOGICAL

MVA-BN-Brachyury

MVA-BN-Brachyury will be administered subcutaneously (2 doses 2 weeks apart).

BIOLOGICAL

FPV-Brachyury

FPV-Brachyury will be given 2 weeks after second dose of modified vaccinia Ankara (MVA)-Bavarian Nordic (BN)-Brachyury, then every 4 weeks until 6 months, then every 3 months for 2 years, then every 6 months.

DRUG

Epacadostat

600 mg orally twice daily (1200 MG total).

DRUG

Acetaminophen

Antipyretic medication, orally, prior to infusion, up to 650mg.

DRUG

Ibuprofen

Antipyretic medication, orally, prior to infusion, up to 600mg.

DRUG

Naproxen

Antipyretic medication, orally, prior to infusion, up to 500mg.

OTHER

Benadryl

50mg orally prior to infusion.

DIAGNOSTIC_TEST

EKG

Baseline and principal investigator discretion.

DIAGNOSTIC_TEST

Bone scan

Restaging every 12 weeks.

DIAGNOSTIC_TEST

CT chest, abdomen and pelvis

Every 12 weeks after start of therapy.

DIAGNOSTIC_TEST

MRI

If clinically indicated.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• James L Gulley, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-05-01

Primary Completion

2024-10-08

Completion

2024-10-08

FDA Drug

Yes

Countries

• United States

Study Locations