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 range18 Years – 120 Years

SexALL

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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

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 range18 Years – 120 Years

SexALL

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