Trial Outcomes & Findings for Safety and Tolerability of a Modified Vaccinia Ankara (MVA)-Based Vaccine Modified to Express Brachyury and T-cell Costimulatory Molecules (MVA-Brachyury-TRICOM) (NCT NCT02179515)

Last Updated: 2021-01-26

Results Overview

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event 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, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

38 participants

Primary outcome timeframe

Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.

Results posted on

2021-01-26

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU Participants received Modified Vaccinia Ankara (MVA)-brachyury-modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU Participants received Modified Vaccinia Ankara (MVA)-brachyury-modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOMvaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU Participants received Modified Vaccinia Ankara (MVA)-brachyury-modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Overall Study STARTED	3	17	18
Overall Study COMPLETED	1	1	4
Overall Study NOT COMPLETED	2	16	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU Participants received Modified Vaccinia Ankara (MVA)-brachyury-modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU Participants received Modified Vaccinia Ankara (MVA)-brachyury-modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOMvaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU Participants received Modified Vaccinia Ankara (MVA)-brachyury-modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Overall Study switched to alternative treatment	0	1	1
Overall Study Death	0	1	1
Overall Study refused further treatment	0	3	4
Overall Study Disease progression on study	2	11	8

Baseline Characteristics

Safety and Tolerability of a Modified Vaccinia Ankara (MVA)-Based Vaccine Modified to Express Brachyury and T-cell Costimulatory Molecules (MVA-Brachyury-TRICOM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=17 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=18 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Total n=38 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants	27 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Age, Continuous	61.17 years STANDARD_DEVIATION 3.4 • n=5 Participants	60.92 years STANDARD_DEVIATION 11.61 • n=7 Participants	60.31 years STANDARD_DEVIATION 12.38 • n=5 Participants	60.65 years STANDARD_DEVIATION 11.38 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	18 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants	20 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	17 Participants n=7 Participants	18 Participants n=5 Participants	38 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	14 Participants n=7 Participants	14 Participants n=5 Participants	31 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	3 participants n=5 Participants	17 participants n=7 Participants	18 participants n=5 Participants	38 participants n=4 Participants
Cancer Diagnosis Chordoma	2 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Cancer Diagnosis Ovarian Ca	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Cancer Diagnosis Pancreatic Ca	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Cancer Diagnosis Colon Ca	0 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Cancer Diagnosis Lung Ca	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Cancer Diagnosis Breast Ca	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Cancer Diagnosis Prostate Ca	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Cancer Diagnosis Cholangiocarcinoma	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Prior Treatments 1 Prior Treatment	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants
Prior Treatments 2 Prior Treatments	0 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	12 Participants n=4 Participants
Prior Treatments 3 Prior Treatments	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants
Prior Treatments 4 Prior Treatments	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Prior Treatments 5 Prior Treatments	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Prior Treatments No prior systemic therapy	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.

Outcome measures

Outcome measures
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=17 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=18 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	3 Participants	14 Participants	17 Participants

PRIMARY outcome

Timeframe: 28 days following the first injection of vaccine.

Dose-limiting toxicity (DLT) will be defined as any one of the following: Any grade ≥ 3 hematologic toxicity or grade ≥ 3 non-hematologic toxicity that is possibly, probably, or definitely related to study drug, except transient (≤ 48 hour) grade 3 fatigue, local reactions, flu-like symptoms, fever, headache, and laboratory abnormalities that are not associated with organ pathology. Also any ≥ grade 2 allergic and ≥ grade 2 autoimmune reaction(s) (except endocrine-related immune toxicity) will be defined as a DLT. Any grade 3 autoimmune endocrine-related toxicity that has not resolved clinically within 7 days of initiating therapy will also be defined as a DLT. Generalized erythroderma or macular or papular rash lasting less than 7 days and not associated with desquamation will not be DLTs.

Outcome measures

Outcome measures
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=17 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=18 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Number of Participants With Dose-Limiting Toxicities (DLT)	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: First 28 days of treatment.

The MTD will be the dose level at which no greater than 1/6 patients have a dose-limiting toxicity (DLT), and the next higher dose level has at least 2 patients with a DLT.

Outcome measures

Outcome measures
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=38 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Maximum Tolerated Dose (MTD)	NA 10^8 IU The MTD was not reached.	—	—

PRIMARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.

Population: Only one Grade 3 adverse event (diarrhea) possibly related to vaccine occurred on this trial; and no Grade 4 and 5 adverse events possibly related to vaccine.

Number of participants with Grade 3 or greater adverse events possibly related to vaccine assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe or medically significant but not immediately life-threatening. Grade 4 is life threatening consequences, and Grade 5 is death related to adverse event.

Outcome measures

Outcome measures
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=17 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=18 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Number of Participants With Grade 3 or Greater Adverse Events Possibly Related to Vaccine	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (pre-vaccination), approximately day 29 (after 1 vaccination), approximately day 57 (after 2 vaccinations), and approximately day 85 (after 3 vaccinations)

Population: Sufficient peripheral blood mononuclear cells (PBMCs) were available before and after vaccination from 34 of 38 patients to analyze brachyury-specific CD4 and CD8 T-cell responses.

A fluorescence activated cell sorting (FACS)-based assay for cluster of differentiation 4 (CD4) or cluster of differentiation 8 (CD8) T-cells expressing the cytokines interferon (IFN) gamma, interleukin 2 (IL2), and tumor necrosis factor (TNF) alpha, and/or cluster of differentiation 107a (CD107a) (a marker for lytic potential) was used to determine the numbers of participants showing development or enhancement of the level of brachyury-specific T-cells after vaccination.

Outcome measures

Outcome measures
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=15 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=16 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations CD107a + CD4 T-cell response (d29 vs pre)	0 Participants	4 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IFN gamma + CD4 T-cell response (d29 vs pre)	1 Participants	2 Participants	1 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations TNF alpha + CD4 T-cell response (d29 vs pre)	0 Participants	4 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IFN gamma + CD8 T-cell response (d29 vs pre)	0 Participants	6 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IL2 + CD8 T-cell response (d29 vs pre)	0 Participants	0 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations TNF alpha + CD8 T-cell response (d29 vs pre)	1 Participants	4 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations Any T-cell response (d29 vs pre)	1 Participants	9 Participants	6 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations CD107a + CD4 T-cell response (d57 vs pre)	0 Participants	3 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IFN gamma + CD4 T-cell response (d57 vs pre)	0 Participants	0 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IL2 + CD4 T-cell response (d57 vs pre)	0 Participants	1 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations CD107a + CD8 T-cell response (d57 vs pre)	0 Participants	3 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IFN gamma + CD8 T-cell response (d57 vs pre)	0 Participants	2 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IL2 + CD8 T-cell response (d57 vs pre)	0 Participants	0 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations TNF alpha + CD8 T-cell response (d57 vs pre)	0 Participants	5 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations Any T-cell response (d57 vs pre)	0 Participants	6 Participants	10 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IFN gamma + CD4 T-cell response (d85 vs pre)	0 Participants	1 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IL2 + CD4 T-cell response (d85 vs pre)	0 Participants	3 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations TNF alpha + CD4 T-cell response (d85 vs pre)	0 Participants	1 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations CD107a + CD8 T-cell response (d85 vs pre)	0 Participants	2 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IL2 + CD8 T-cell response (d85 vs pre)	0 Participants	0 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations TNF alpha + CD8 T-cell response (d85 vs pre)	0 Participants	1 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IL2 + CD4 T-cell response (d29 vs pre)	1 Participants	1 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations CD107a + CD8 T-cell response (d29 vs pre)	1 Participants	1 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations IFN gamma + CD8 T-cell response (d85 vs pre)	0 Participants	0 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations Any T-cell response (d85 vs pre)	0 Participants	5 Participants	9 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations TNF alpha + CD4 T-cell response (d57 vs pre)	0 Participants	0 Participants	0 Participants
Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations CD107a + CD4 T-cell response (d85 vs pre)	0 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre (Baseline), and approximately D29 (Post 1 vaccination) and D85 (post 3 vaccinations)

Population: Sufficient peripheral blood mononuclear cells (PBMCs) were available before and after vaccination from 36 of 38 patients to analyze peripheral immune cell subsets.

Blood samples collected were analyzed by multicolor flow cytometry in PBMCs for cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), Natural Killer (NK), Natural Killer T (NKT), conventional dendritic cell (cDC), plasmacytoid dendritic cell (pDC), myeloid-derived suppressor cell (MDSC) and Tregs. Changes in levels PBMC subsets was a descriptive result with median and interquartile range reported. No formal statistical analysis by dose level was performed given the small sample size.

Outcome measures

Outcome measures
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=16 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=17 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations CD4 Pre	24.31 Percentage of Total PBMC's Interval 14.78 to 38.24	32.64 Percentage of Total PBMC's Interval 27.63 to 40.74	32.89 Percentage of Total PBMC's Interval 22.61 to 37.37
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations CD4 D29	23.68 Percentage of Total PBMC's Interval 13.15 to 36.09	34.99 Percentage of Total PBMC's Interval 23.61 to 39.35	29.86 Percentage of Total PBMC's Interval 20.99 to 36.08
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations CD4 D85	27.70 Percentage of Total PBMC's Interval 13.09 to 39.84	30.35 Percentage of Total PBMC's Interval 25.55 to 36.67	29.87 Percentage of Total PBMC's Interval 25.77 to 36.65
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations CD8 Pre	7.51 Percentage of Total PBMC's Interval 4.9 to 14.31	16.85 Percentage of Total PBMC's Interval 10.2 to 23.58	12.27 Percentage of Total PBMC's Interval 9.28 to 16.34
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations CD8 D29	7.83 Percentage of Total PBMC's Interval 3.73 to 13.43	16.28 Percentage of Total PBMC's Interval 9.55 to 24.45	10.96 Percentage of Total PBMC's Interval 9.18 to 17.43
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations Treg Pre	2.19 Percentage of Total PBMC's Interval 1.0 to 2.41	1.50 Percentage of Total PBMC's Interval 1.21 to 1.93	1.07 Percentage of Total PBMC's Interval 0.77 to 1.53
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations Treg D29	1.71 Percentage of Total PBMC's Interval 1.23 to 1.98	1.40 Percentage of Total PBMC's Interval 1.2 to 1.78	1.34 Percentage of Total PBMC's Interval 0.88 to 1.65
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations CD8 D85	10.92 Percentage of Total PBMC's Interval 5.71 to 13.99	17.17 Percentage of Total PBMC's Interval 12.29 to 26.14	13.99 Percentage of Total PBMC's Interval 11.78 to 20.43
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations Treg D85	2.09 Percentage of Total PBMC's Interval 1.19 to 2.3	1.26 Percentage of Total PBMC's Interval 0.8 to 1.65	1.22 Percentage of Total PBMC's Interval 0.74 to 1.63
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations B cells Pre	15.89 Percentage of Total PBMC's Interval 10.45 to 21.33	7.76 Percentage of Total PBMC's Interval 5.32 to 15.31	10.41 Percentage of Total PBMC's Interval 6.2 to 12.44
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations B cells D29	15.46 Percentage of Total PBMC's Interval 10.5 to 20.42	7.52 Percentage of Total PBMC's Interval 5.54 to 15.24	8.56 Percentage of Total PBMC's Interval 6.55 to 11.97
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations B cells D85	14.54 Percentage of Total PBMC's Interval 12.17 to 16.91	6.49 Percentage of Total PBMC's Interval 5.32 to 11.82	10.26 Percentage of Total PBMC's Interval 6.3 to 14.01
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations NK cells Pre	6.47 Percentage of Total PBMC's Interval 5.35 to 8.33	6.07 Percentage of Total PBMC's Interval 4.23 to 9.07	8.93 Percentage of Total PBMC's Interval 4.74 to 13.82
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations NK cells D29	7.51 Percentage of Total PBMC's Interval 5.4 to 8.28	7.32 Percentage of Total PBMC's Interval 5.82 to 11.97	12.34 Percentage of Total PBMC's Interval 6.9 to 18.94
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations NK cells D85	10.30 Percentage of Total PBMC's Interval 6.98 to 18.52	7.83 Percentage of Total PBMC's Interval 6.5 to 9.57	12.29 Percentage of Total PBMC's Interval 7.55 to 14.45
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations NK-T cells Pre	0.29 Percentage of Total PBMC's Interval 0.24 to 0.52	1.69 Percentage of Total PBMC's Interval 1.2 to 5.93	1.90 Percentage of Total PBMC's Interval 1.0 to 2.78
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations NK-T cells D29	0.35 Percentage of Total PBMC's Interval 0.31 to 0.55	2.06 Percentage of Total PBMC's Interval 0.95 to 6.09	2.23 Percentage of Total PBMC's Interval 0.85 to 2.75
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations NK-T cells D85	0.42 Percentage of Total PBMC's Interval 0.25 to 0.43	2.14 Percentage of Total PBMC's Interval 0.94 to 6.48	2.03 Percentage of Total PBMC's Interval 0.74 to 2.91
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations cDC Pre	0.24 Percentage of Total PBMC's Interval 0.22 to 0.58	0.23 Percentage of Total PBMC's Interval 0.13 to 0.31	0.27 Percentage of Total PBMC's Interval 0.2 to 0.4
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations cDC D29	0.46 Percentage of Total PBMC's Interval 0.27 to 0.54	0.18 Percentage of Total PBMC's Interval 0.12 to 0.27	0.22 Percentage of Total PBMC's Interval 0.17 to 0.35
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations cDC D85	0.28 Percentage of Total PBMC's Interval 0.14 to 0.52	0.18 Percentage of Total PBMC's Interval 0.15 to 0.24	0.22 Percentage of Total PBMC's Interval 0.16 to 0.32
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations pDC Pre	0.13 Percentage of Total PBMC's Interval 0.12 to 0.25	0.15 Percentage of Total PBMC's Interval 0.1 to 0.22	0.17 Percentage of Total PBMC's Interval 0.1 to 0.36
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations pDC D29	0.16 Percentage of Total PBMC's Interval 0.15 to 0.24	0.17 Percentage of Total PBMC's Interval 0.11 to 0.21	0.22 Percentage of Total PBMC's Interval 0.12 to 0.36
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations pDC D85	0.07 Percentage of Total PBMC's Interval 0.07 to 0.39	0.15 Percentage of Total PBMC's Interval 0.12 to 0.21	0.23 Percentage of Total PBMC's Interval 0.14 to 0.3
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations MDSC Pre	13.17 Percentage of Total PBMC's Interval 6.84 to 19.5	7.11 Percentage of Total PBMC's Interval 4.86 to 10.69	7.04 Percentage of Total PBMC's Interval 4.92 to 10.18
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations MDSC D29	8.53 Percentage of Total PBMC's Interval 6.42 to 10.63	6.69 Percentage of Total PBMC's Interval 4.27 to 11.29	7.66 Percentage of Total PBMC's Interval 4.91 to 10.54
Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations MDSC D85	8.34 Percentage of Total PBMC's Interval 6.52 to 10.16	9.15 Percentage of Total PBMC's Interval 5.11 to 11.94	8.83 Percentage of Total PBMC's Interval 4.58 to 11.42

SECONDARY outcome

Timeframe: Pre (Baseline), and approximately D29 (Post 1 vaccination), D57 (post 2 vaccinations) and D85 (post 3 vaccinations)

Population: Sufficient serum was available before and after vaccination from 34 of 38 patients to analyze anti-brachyury antibodies.

A positive brachyury antibody titer consisted of an absorbance to brachyury protein that was twice that obtained with the negative control protein Bovine serum albumin (BSA). A positive titer after vaccination may be indicative of an immune response to the vaccine.

Outcome measures

Outcome measures
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=15 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=16 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Number of Participants With Positive Anti-Brachyury Antibodies Anti-Brachyury Antibodies Pre	0 Participants	1 Participants	2 Participants
Number of Participants With Positive Anti-Brachyury Antibodies Anti-Brachyury Antibodies D29	0 Participants	1 Participants	3 Participants
Number of Participants With Positive Anti-Brachyury Antibodies Anti-Brachyury Antibodies D57	0 Participants	1 Participants	5 Participants
Number of Participants With Positive Anti-Brachyury Antibodies Anti-Brachyury Antibodies D85	0 Participants	1 Participants	4 Participants

SECONDARY outcome

Timeframe: Pre (Baseline), and approximately D29 (Post 1 vaccination), and D85 (post 3 vaccinations)

Population: Sufficient serum was available before and after vaccination from 36 of 38 patients to analyze serum cytokines and soluble factors.

Serum levels of Soluble CD27 (sCD27) were determined by enzyme-linked immunosorbent assay (ELISA) pre and post vaccination. Changes in levels of serum cytokines and soluble factors was a descriptive result with median and interquartile range reported. No formal statistical analysis by dose level was performed given the small sample size.

Outcome measures

Outcome measures
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=16 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=17 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Changes in Serum Cytokines Soluble CD27 (sCD27) and Soluble Factors sCD27 Pre	20.53 U/mL Interval 1.2 to 51.33	19.34 U/mL Interval 11.24 to 23.57	12.10 U/mL Interval 7.42 to 18.88
Changes in Serum Cytokines Soluble CD27 (sCD27) and Soluble Factors sCD27 D29	25.65 U/mL Interval 16.3 to 47.38	18.40 U/mL Interval 8.02 to 27.1	15.12 U/mL Interval 11.95 to 25.82
Changes in Serum Cytokines Soluble CD27 (sCD27) and Soluble Factors sCD27 D85	22.35 U/mL Interval 19.03 to 24.15	14.50 U/mL Interval 9.06 to 25.38	16.33 U/mL Interval 12.1 to 25.99

SECONDARY outcome

Timeframe: Pre (Baseline), and approximately D29 (Post 1 vaccination), and D85 (post 3 vaccinations)

Population: Sufficient serum was available before and after vaccination from 36 of 38 patients to analyze serum cytokines and soluble factors.

Serum levels of sCD40L, were determined by enzyme-linked immunosorbent assay (ELISA) pre and post vaccination. Changes in levels of serum cytokines and soluble factors was a descriptive result with median and interquartile range reported. No formal statistical analysis by dose level was performed given the small sample size.

Outcome measures

Outcome measures
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=16 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=17 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Changes in Serum Cytokines Soluble CD40 Ligand (sCD40L) and Soluble Factors sCD40L D85	10.33 ng/mL Interval 1.4 to 18.35	17.54 ng/mL Interval 9.77 to 20.32	17.90 ng/mL Interval 14.03 to 21.75
Changes in Serum Cytokines Soluble CD40 Ligand (sCD40L) and Soluble Factors sCD40L Pre	4.76 ng/mL Interval 1.55 to 20.34	17.52 ng/mL Interval 11.98 to 22.03	18.94 ng/mL Interval 14.63 to 26.29
Changes in Serum Cytokines Soluble CD40 Ligand (sCD40L) and Soluble Factors sCD40L D29	17.11 ng/mL Interval 1.0 to 19.79	17.81 ng/mL Interval 14.92 to 20.27	16.05 ng/mL Interval 11.25 to 19.85

SECONDARY outcome

Timeframe: Pre (Baseline), and approximately D29 (Post 1 vaccination), and D85 (post 3 vaccinations)

Population: Sufficient serum was available before and after vaccination from 36 of 38 patients to analyze serum cytokines and soluble factors.

Serum levels of sCD27, sCD40L, and the ratio of sCD27:sCD40L were determined by enzyme-linked immunosorbent assay (ELISA) pre and post vaccination. Changes in levels of serum cytokines and soluble factors was a descriptive result with median and interquartile range reported. No formal statistical analysis by dose level was performed given the small sample size.

Outcome measures

Outcome measures
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=16 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=17 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Changes in the Ratio of Serums Soluble CD27 (sCD27):Soluble CD40 Ligand (sCD40L) sCD27:sCD40L Pre	4.31 Ratio Interval 0.06 to 33.06	1.02 Ratio Interval 0.56 to 1.94	0.64 Ratio Interval 0.35 to 1.28
Changes in the Ratio of Serums Soluble CD27 (sCD27):Soluble CD40 Ligand (sCD40L) sCD27:sCD40L D29	1.50 Ratio Interval 0.82 to 47.38	1.25 Ratio Interval 0.42 to 2.06	0.82 Ratio Interval 0.59 to 2.13
Changes in the Ratio of Serums Soluble CD27 (sCD27):Soluble CD40 Ligand (sCD40L) sCD27:sCD40L D85	1.84 Ratio Interval 1.22 to 17.28	1.05 Ratio Interval 0.53 to 2.71	0.89 Ratio Interval 0.69 to 1.47

SECONDARY outcome

Timeframe: Pre (Baseline), and approximately D29 (Post 1 vaccination), and D85 (post 3 vaccinations)

Population: Sufficient serum was available before and after vaccination from 36 of 38 patients to analyze serum cytokines and soluble factors.

Serum levels of IL-2, IL-4, IL-10, and IFNg were determined by enzyme-linked immunosorbent assay (ELISA) pre and post vaccination. Changes in levels of serum cytokines and soluble factors was a descriptive result with median and interquartile range reported. No formal statistical analysis by dose level was performed given the small sample size.

Outcome measures

Outcome measures
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=16 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=17 Participants Participants received Modified Vaccinia Ankara (MVA)-brachyury-TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IL-10 Pre	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IL-2 Pre	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IL-2 D29	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IL-2 D85	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IL-10 D29	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IL-10 D85	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IL-4 Pre	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IL-4 D29	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IL-4 D85	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0	0.00 pg/mL Interval 0.0 to 0.0
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IFNg Pre	1.42 pg/mL Interval 0.0 to 26.11	0.16 pg/mL Interval 0.06 to 1.42	1.23 pg/mL Interval 0.0 to 94.87
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IFNg D29	1.23 pg/mL Interval 0.0 to 31.59	0.84 pg/mL Interval 0.26 to 2.17	0.74 pg/mL Interval 0.0 to 131.9
Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) IFNg D85	1.13 pg/mL Interval 0.16 to 28.9	0.55 pg/mL Interval 0.26 to 2.1	1.62 pg/mL Interval 0.0 to 130.2

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 -3 years

Population: Tissue collection was optional and insufficient tissue was obtained to perform this analysis.

Correlation of brachyury expression in tissue samples with clinical outcomes.

Outcome measures

Outcome data not reported

Adverse Events

Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU

Serious events: 4 serious events

Other events: 14 other events

Deaths: 1 deaths

Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU

Serious events: 2 serious events

Other events: 17 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 1 - 1 Injection - Total Dose 2 x 10^8 IU n=3 participants at risk Participants received Modified Vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine administered subcutaneously as 1 injection (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 2 - 2 Injections - Total Dose 4 x 10^8 IU n=17 participants at risk Participants received Modified Vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine administered subcutaneously as 2 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.	Dose Level 3 - 4 Injections - Total Dose 8 x 10^8 IU n=18 participants at risk Participants received Modified Vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine administered subcutaneously as 4 injections (I injection = 2 x 10\^8 IU) of study drug at monthly (28 days +/- 4 days) intervals for 3 months. Patients with stable disease may continue to receive vaccine for up to 6 monthly doses.
Gastrointestinal disorders Colonic obstruction	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	0.00% 0/17 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	0.00% 0/18 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.
Injury, poisoning and procedural complications Hip fracture	33.3% 1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	0.00% 0/17 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	0.00% 0/18 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	5.9% 1/17 • Number of events 1 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	0.00% 0/18 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.
Gastrointestinal disorders Colitis	0.00% 0/3 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	5.9% 1/17 • Number of events 1 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	0.00% 0/18 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	5.9% 1/17 • Number of events 1 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	0.00% 0/18 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.
Infections and infestations Lung infection	0.00% 0/3 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	5.9% 1/17 • Number of events 1 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	0.00% 0/18 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.
General disorders Pain	0.00% 0/3 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	0.00% 0/17 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.
Infections and infestations Sepsis	0.00% 0/3 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	0.00% 0/17 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.	5.6% 1/18 • Number of events 1 • Date treatment consent signed to date off study, approximately 9 months and 6 days for DL1, 17 months and 3 days for DL2, and 23 months and 13 days for DL3.

Other adverse events

Additional Information

Dr. James Gulley

National Cancer Institute

Phone: 301-480-8870

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place