CompletedPhase 1/2

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

United States59 participantsStarted 2018-05-01

Plain-language 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.

Who can participate

Age range

18 Years – 120 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

-Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer
-prostate-specific antigen (PSA) progression defined by sequence of rising values separated by greater than 1 week (2 separate increasing values over a minimum of 1 ng/ml (Prostate Cancer Clinical Trials 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 the day prior to enrollment.

Exclusion criteria

-Participants with a QTc corrected for heart rate by Fridericia's formula (QTcF) interval \> 480 milliseconds at the screening are excluded. In the event that a single QTcF is \> 480 milliseconds, the subject may enroll if the average QTcF for the 3 electrocardiogram (ECG's) is \< 480 milliseconds. For subjects with an intraventricular conduction delay (QRS interval \> 120 milliseconds), the corrected JT interval, (JTc) interval may be used in place of the QTc. The JTc must be \< 340 milliseconds if JTc is used in place of the QTc. QTc prolongation due to pacemaker may enroll if the JTc is normal.

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Clinical Benefit With Any of a Set of 3 Possible Treatments for Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Reported With an 80% Confidence Interval

Timeframe: From enrollment up to 49 weeks

Clinical Benefit(Objective Response if Measurable Disease by Response Evaluation Criteria in Solid Tumors v1.1)With Any of 3 Possible Treatments for Participants With Metastatic Castration-resistant Prostate Cancer Reported With a 95% Confidence Interval

Timeframe: From enrollment up to 49 weeks

Phase I/II: Number of Participants With Grades 3, 4, and/or 5 Serious and/or Non-serious Dose-limiting Toxicities (DLT)

Timeframe: Within 21 days of the start of treatment

Trial details

NCT IDNCT03493945

SponsorNational Cancer Institute (NCI)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2024-10-08

Results submitted2025-04-14

View on ClinicalTrials.gov More Metastatic Castration-resistant Prostate Cancer trials

Plain-language summary

Who can participate

Age range

18 Years – 120 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

-Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer
-prostate-specific antigen (PSA) progression defined by sequence of rising values separated by greater than 1 week (2 separate increasing values over a minimum of 1 ng/ml (Prostate Cancer Clinical Trials 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 the day prior to enrollment.

Exclusion criteria

-Participants with a QTc corrected for heart rate by Fridericia's formula (QTcF) interval \> 480 milliseconds at the screening are excluded. In the event that a single QTcF is \> 480 milliseconds, the subject may enroll if the average QTcF for the 3 electrocardiogram (ECG's) is \< 480 milliseconds. For subjects with an intraventricular conduction delay (QRS interval \> 120 milliseconds), the corrected JT interval, (JTc) interval may be used in place of the QTc. The JTc must be \< 340 milliseconds if JTc is used in place of the QTc. QTc prolongation due to pacemaker may enroll if the JTc is normal.

What they're measuring

Clinical Benefit With Any of a Set of 3 Possible Treatments for Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Reported With an 80% Confidence Interval

Timeframe: From enrollment up to 49 weeks

Phase I/II: Number of Participants With Grades 3, 4, and/or 5 Serious and/or Non-serious Dose-limiting Toxicities (DLT)

Timeframe: Within 21 days of the start of treatment