Phase I/II Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, N-803 and Epacadostat (QuEST1)
A Phase I/II Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, N-803 and Epacadostat (QuEST1)
2 other identifiers
interventional
59
1 country
1
Brief 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.
- 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2018
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 10, 2018
CompletedFirst Posted
Study publicly available on registry
April 11, 2018
CompletedStudy Start
First participant enrolled
May 1, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 8, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 8, 2024
CompletedResults Posted
Study results publicly available
June 8, 2025
CompletedSeptember 30, 2025
September 1, 2025
6.4 years
April 10, 2018
April 14, 2025
September 11, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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
Objective clinical response and/or prostate-specific antigen (PSA) decline of \>=30% sustained for a minimum of 21 days. Any of these is considered 'clinical benefit.' Objective response was assessed by the response evaluation criteria in solid tumors (RECIST) 1.1. Complete response (CR) is disappearance of all non-target lesions and normalization of tumor marker level. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions. Three treatments evaluated are: Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824), Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824) + Anktiva (N-803), and Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824) + Anktiva (N-803) + Epacadostat.
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
Objective response was assessed by the response evaluation criteria in solid tumors (RECIST) 1.1. Complete response (CR) is disappearance of all non-target lesions and normalization of tumor marker level. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions. Three treatments evaluated are: Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824), Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824) + Anktiva (N-803), and Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824) + Anktiva (N-803) + Epacadostat.
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)
A DLT is defined as any of the following adverse events (AE) possibly related to study drugs that occur within 21 days of the start of treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 3 is moderate. Grade 4 is life-threatening, and Grade 5 is death related to AE. A DLT is any grade ≥ 4 hematologic toxicity or grade 3 thrombocytopenia with associated bleeding; any grade ≥ 3 non-hematologic toxicity, except for any of the following: transient (≤ 48 hour) grade 3 fatigue, local reactions, flu-like symptoms, fever, headache, or nausea, emesis, and diarrhea; or CTCAE Grade 3 skin toxicity lasting less than five days. A non-serious AE is any untoward medical occurrence. A serious AE is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, or congenital anomaly/birth defect.
Within 21 days of the start of treatment
Secondary Outcomes (3)
6-month Progression Free Survival (PFS) Probability
6-months
Number of Participants With Grades 1, 2, 3, and 4 Non-serious Adverse Events Related to Treatment Treated With Combinations and Bintrafusp Alfa (M7824) + Anktiva (N-803)
3 weeks dose-limiting toxicity (DLT) period
Number of Participants With Grades 3, 4, and/or 5 Serious Adverse Events Related to Treatment Treated With Combinations and Bintrafusp Alfa (M7824) + Anktiva (N-803)
3 weeks dose-limiting toxicity (DLT) period
Other Outcomes (1)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Adverse Events were monitored/assessed from the first study intervention, up to 49 weeks.
Study Arms (7)
Arm 1.1 Bintrafusp alfa (M7824) + Anktiva (N-803)
EXPERIMENTALBintrafusp alfa (M7824) + Anktiva (N-803)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
EXPERIMENTALBintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
EXPERIMENTALBintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
EXPERIMENTALBintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
EXPERIMENTALBintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
EXPERIMENTALBintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
EXPERIMENTALBintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Interventions
1,200 mg intravenous (IV) once every 2 weeks.
8-15 mcg/kg subcutaneous every 2 weeks.
MVA-BN-Brachyury will be administered subcutaneously (2 doses 2 weeks apart).
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.
600 mg orally twice daily (1200 MG total).
Antipyretic medication, orally, prior to infusion, up to 650mg.
Antipyretic medication, orally, prior to infusion, up to 600mg.
Antipyretic medication, orally, prior to infusion, up to 500mg.
50mg orally prior to infusion.
Baseline and principal investigator discretion.
Restaging every 12 weeks.
Every 12 weeks after start of therapy.
If clinically indicated.
Eligibility Criteria
You may qualify if:
- Participants must have histologically or cytologically confirmed any solid tumor (Cohort 1) or castration-resistant prostate cancer (CRPC), Cohorts 2A, 2D and 2R).
- For the Cohort 1, eligible participants must have a histologically, cytologically or radiographically proven metastatic or locally advanced solid tumor of any type, for which there is no curative standard therapy or standard therapy has failed.
- Castrate testosterone level (less than 50ng/dl or 1.7nmol/L). (Participants with a malignancy other than prostate cancer are excluded from this criterion).
- Radiological confirmation of metastatic disease, or
- 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
- 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.
- Asymptomatic or mildly symptomatic form prostate cancer; no use of regularly scheduled opiate analgesics for prostate cancer-related pain. (Participants with a malignancy other than prostate cancer are excluded from this criterion).
- Participants must agree to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy. (Participants with a malignancy other than prostate cancer are excluded from this criterion). Participants may also continue oral androgen receptor antagonist/anti-androgen therapy (e.g. enzalutamide or abiraterone) unless enrolling to Arm 2.3A or 2.3B due to concerns regarding Cytochrome P450 (CYP)mediated drug-drug interactions epacadostat.
- Participants must have had the following prior therapy:
- Testosterone lowering therapy for castration-resistant prostate cancer (CRPC)
- In addition to continuation of androgen deprivation therapy (ADT) (unless status post bilateral orchiectomy) eligible patients must have received and had PSA or radiographic progression on enzalutamide (or other oral androgen receptor antagonist e.g. darolutamide or apalutamdide) or abiraterone acetate.
- Participants who have tumors known to be microsatellite instability high/mismatch repair deficient or tumor mutational burden high must have received prior pembrolizumab.
- Participants with known pathogenic homologous recombination repair mutations for which there is evidence of benefit with poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors (e.g. BReast CAncer gene 1 (BRCA1). BReast CAncer gene 2 (BRCA2), ataxia-telangiectasia mutated (ATM) must have received prior PARP inhibitor.
- Age greater than or equal to 18 years.
- +11 more criteria
You may not qualify if:
- Participants who are immunocompromised as follows:
- Human immunodeficiency virus positivity due to the potential for decreased tolerance, and potential to be at risk for severe side effects with immunotherapies. These concerns are relevant to all drugs, as drug-drug interactions among antiretrovirals and immunotherapies are yet uncharacterized.
- Chronic administration (defined as daily or every other day for continued use greater than 14 days) of systemic corticosteroids or other immune suppressive drugs, within 28 days before treatment on study. Nasal, or inhaled steroid, topical steroid creams and eye drops for small body areas are allowed. Physiologic doses of steroids are permitted, e.g., a participant taking hydrocortisone for adrenal insufficiency or a patient recently on abiraterone (administered with 10 mg of prednisone daily) who is tapering off of prednisone is allowed to continue that taper.
- Participants who have undergone 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 or are not excluded if the condition is well controlled.
- Prostate cancer participants with a history of brain/leptomeningeal metastasis, since these participants have a very poor prognosis, and immunotherapy may take time to lead to beneficial clinical effects. Participants with brain or CNS metastases enrolling to arm 1.1 are eligible if they are 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 in the cohort the subject will be enrolled into.
- Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin).
- Any condition which, in the opinion of the investigator, would prevent full participation in this trial (including the long-term follow-up), or would interfere with the evaluation of the trial endpoints.
- Participants with prior investigational drug, chemotherapy, immunotherapy or any prior radiotherapy (except for palliative bone directed therapy) within the past 28 days prior to enrollment, except if the investigator has assessed that all residual treatment-related toxicities have resolved or are minimal and feel the participant is otherwise suitable for enrollment.
- 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 (Systolic blood pressure (SBP) \>170/ diastolic blood pressure (DBP)\>105) or psychiatric illness/social situations within 12 months that would limit compliance with study requirements.
- Use of herbal products that may decrease PSA levels (e.g., saw palmetto)
- Participants who have had cytotoxic chemotherapy for metastatic castration-resistant prostate cancer within the past 3 months. (Participants who have had docetaxel for metastatic castration sensitive per Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (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.)
- Participants who have undergone major surgery within 4 weeks of enrollment. A biopsy will not preclude a participant from starting study.
- Participants with a history of hepatitis B (HBV) are excluded due to potential risk for viral reactivation and resulting liver injury in persons with latent HBV
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (2)
Fabian KP, Padget MR, Fujii R, Schlom J, Hodge JW. Differential combination immunotherapy requirements for inflamed (warm) tumors versus T cell excluded (cool) tumors: engage, expand, enable, and evolve. J Immunother Cancer. 2021 Feb;9(2):e001691. doi: 10.1136/jitc-2020-001691.
PMID: 33602696DERIVEDRedman JM, Steinberg SM, Gulley JL. Quick efficacy seeking trial (QuEST1): a novel combination immunotherapy study designed for rapid clinical signal assessment metastatic castration-resistant prostate cancer. J Immunother Cancer. 2018 Sep 18;6(1):91. doi: 10.1186/s40425-018-0409-8.
PMID: 30227893DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. James L. Gulley
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
James L Gulley, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
April 10, 2018
First Posted
April 11, 2018
Study Start
May 1, 2018
Primary Completion
October 8, 2024
Study Completion
October 8, 2024
Last Updated
September 30, 2025
Results First Posted
June 8, 2025
Record last verified: 2025-09
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 Genomic Data Sharing (GDS) plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).