Phase I/II Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, N-803 and Epacadostat (QuEST1)
Summary
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
.076; 0.292; 0 | — |
| PRIMARY 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 |
0; 0; 0; 0; 0.33; 0 | — |
| PRIMARY Phase I/II: Number of Participants With Grades 3, 4, and/or 5 Serious and/or Non-serious Dose-limiting Toxicities (DLT) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY 6-month Progression Free Survival (PFS) Probability |
0.354; 0.348; NA | — |
| SECONDARY 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) |
0; 0; 0; 4; 0; 0 | — |
| SECONDARY 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) |
0; 0; 0; 1; 0; 0 | — |
Eligibility Criteria
- INCLUSION CRITERIA:
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
OR
--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.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
Participants must have adequate organ and marrow function as defined below:
- Absolute neutrophil count greater than or equal to 1000/mcL
- Platelets greater than or equal to 100,000/mcL
- Hemoglobin greater than or equal to 9.0 g/dL
- Total bilirubin within normal institutional limits; in participants with Gilbert's, less than or equal to 3.0 mg/dL
- Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) s
Data sourced from ClinicalTrials.gov (NCT03493945). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.