Trial Outcomes & Findings for Multi-Targeted Recombinant Ad5 (CEA/MUC1/Brachyury) Based Immunotherapy Vaccine Regimen in People With Advanced Cancer (NCT NCT03384316)

Last Updated: 2020-09-09

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 v5.0). 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

11 participants

Primary outcome timeframe

Date treatment consent signed to date off study, approximately 16 months and 6 days.

Results posted on

2020-09-09

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin-1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Overall Study STARTED	6	5
Overall Study COMPLETED	6	4
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin-1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Overall Study Screen failure	0	1

Baseline Characteristics

Serum for antibody analysis was only available for 5/6 participants in the Dose Level 1 Cohort, and 3/5 participants in the Expansion Cohort.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 Participants Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin-1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=5 Participants ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin-1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Total n=11 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=11 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=6 Participants	5 Participants n=5 Participants	10 Participants n=11 Participants
Age, Categorical >=65 years	1 Participants n=6 Participants	0 Participants n=5 Participants	1 Participants n=11 Participants
Age, Continuous	50.3 years STANDARD_DEVIATION 8.1 • n=6 Participants	48.6 years STANDARD_DEVIATION 12.9 • n=5 Participants	49.5 years STANDARD_DEVIATION 10.6 • n=11 Participants
Sex: Female, Male Female	6 Participants n=6 Participants	0 Participants n=5 Participants	6 Participants n=11 Participants
Sex: Female, Male Male	0 Participants n=6 Participants	5 Participants n=5 Participants	5 Participants n=11 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=11 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=6 Participants	5 Participants n=5 Participants	11 Participants n=11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=11 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=11 Participants
Race (NIH/OMB) Asian	2 Participants n=6 Participants	1 Participants n=5 Participants	3 Participants n=11 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=11 Participants
Race (NIH/OMB) Black or African American	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=11 Participants
Race (NIH/OMB) White	4 Participants n=6 Participants	4 Participants n=5 Participants	8 Participants n=11 Participants
Race (NIH/OMB) More than one race	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=11 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=11 Participants
Region of Enrollment United States	6 Participants n=6 Participants	5 Participants n=5 Participants	11 Participants n=11 Participants
Number of Participants with Adenovirus 5-Neutralizing Antibodies	2 Participants n=5 Participants • Serum for antibody analysis was only available for 5/6 participants in the Dose Level 1 Cohort, and 3/5 participants in the Expansion Cohort.	0 Participants n=3 Participants • Serum for antibody analysis was only available for 5/6 participants in the Dose Level 1 Cohort, and 3/5 participants in the Expansion Cohort.	2 Participants n=8 Participants • Serum for antibody analysis was only available for 5/6 participants in the Dose Level 1 Cohort, and 3/5 participants in the Expansion Cohort.

PRIMARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 16 months and 6 days.

Outcome measures

Outcome measures
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 Participants Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=4 Participants ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Number of Participants With Serious and Non-serious Adverse Events	6 Participants	4 Participants

PRIMARY outcome

Timeframe: RP2D was based upon evaluation of DLTs. Participants were followed for DLTs from the first dose of vaccine for 3 weeks.

Population: RP2D was determined in Dose Level 1 cohort.

RP2D is defined as ≤ 1 of 6 of the initial 6 subjects who experience a dose limiting toxicity (DLT), than this dose level will be defined as the RP2D. A DLT is defined as any Grade 3 or greater toxicity that is possibly related to the vaccine and as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 with the exception of transient (≤ 24 hours) Grade 3 flu-like symptoms or fever, which is controlled with medical management (≤ 24 hours) Grade 3 fatigue, skin reactions or rash, headache, nausea, emesis that resolves to Grade ≤ 1 or asymptomatic grade 3 amylase/lipase elevation.

Outcome measures

Outcome measures
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 Participants Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Recommended Phase 2 Dose (RP2D)	500 billion viral particles per indiv. vacc.	—

SECONDARY outcome

Timeframe: Approximately 3.5 months

Objective response is determined by participants whose tumors shrunk after therapy assessed by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 Participants Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=4 Participants ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Number of Participants Who Achieve an Objective Confirmed Complete or Partial Response Assessed by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Confirmed Complete Response	0 Participants	0 Participants
Number of Participants Who Achieve an Objective Confirmed Complete or Partial Response Assessed by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Partial Response	0 Participants	0 Participants

SECONDARY outcome

Timeframe: up to 6 months

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for Partial Response (PR) nor sufficient increase to qualify for Progressive Disease (taking as reference the smallest sum diameters while on study).

Outcome measures

Outcome measures
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 Participants Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=4 Participants ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Number of Patients With Disease Control (Confirmed Response or Stable Disease (SD)) Lasting for at Least 6 Months	1 Participants	1 Participants

SECONDARY outcome

Timeframe: up to 12 months

The amount of time a subject survives without disease progression after treatment. Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum diameters while on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of 5 mm. (Note: the appearance of one or more lesions is also considered progression).

Outcome measures

Outcome measures
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 Participants Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=4 Participants ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Progression-free Survival (PFS)	10 weeks Interval 3.0 to 22.0	9 weeks Interval 6.0 to 30.0

SECONDARY outcome

Timeframe: up to 12 months

OS is defined as the amount of time a subject survives after therapy assessed from the date of first treatment to the date of death (any cause).

Outcome measures

Outcome measures
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 Participants Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=4 Participants ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Overall Survival (OS)	9.5 months Interval 2.0 to There are insufficient events after the median to calculate the upper bound. It is 'not estimable'.	9.5 months Interval 5.0 to There are insufficient events after the median to calculate the upper bound. It is 'not estimable'.

OTHER_PRE_SPECIFIED outcome

Timeframe: up to week 6

Peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry to evaluate anti-tumor response induced by vaccine injection.

Outcome measures

Outcome measures
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 Participants Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=4 Participants ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Number of Participants With a Positive Mucin-1 (MUC-1) Specific T-Cells Immune Response	3 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: up to week 6

Peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry to evaluate anti-tumor response induced by vaccine injection.

Outcome measures

Outcome measures
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 Participants Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=4 Participants ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Number of Participants With a Positive Carcinoembryonic Antigen (CEA) Specific T-Cells Immune Response	2 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: up to week 6

Peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry to evaluate anti-tumor response induced by vaccine injection.

Outcome measures

Outcome measures
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 Participants Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=4 Participants ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Number of Participants With a Positive Brachyury Specific T-Cells Immune Response	1 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From the date of the first dose of vaccine, approximately 3 weeks.

A DLT is defined as any Grade 3 or greater toxicity that is possibly related to the vaccine and as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 with the exception of transient (≤ 24 hours) Grade 3 flu-like symptoms or fever, which is controlled with medical management (≤ 24 hours) Grade 3 fatigue, skin reactions or rash, headache, nausea, emesis that resolves to Grade ≤ 1 or asymptomatic grade 3 amylase/lipase elevation.

Outcome measures

Outcome measures
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 Participants Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=4 Participants ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Number of Dose Limiting Toxicities (DLTs)	0 Toxicities	0 Toxicities

Adverse Events

Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 1 deaths

Expansion Cohort - 5 x 10^11 Viral Particles (VP)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 participants at risk Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=4 participants at risk ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
General disorders Fever	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Infections and infestations Infections and Infestations - Other, Gram-negative bacteremia, 40 degree C fever	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
General disorders Death, NOS	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.

Other adverse events

Additional Information

Dr. Julius Y. Strauss

National Cancer Institute

Phone: 240-858-3999

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dose Level 1 Cohort - 5 x 10^11 Viral Particles (VP) n=6 participants at risk Up to 6 patients will be enrolled on Dose Level 1. If ≤1 of 6 patients experience a dose limiting toxicity, initiation of the Dose Expansion phase will occur. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year	Expansion Cohort - 5 x 10^11 Viral Particles (VP) n=4 participants at risk ≤1 of 6 patients experienced a dose limiting toxicity on Dose Level 1, thus subjects were enrolled in a Dose Expansion phase. ETBX-051; adenoviral brachyury vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-061; adenoviral Mucin -1 (MUC1) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine: immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Metabolism and nutrition disorders Anorexia	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Gastrointestinal disorders Bloating	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
General disorders Chills	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Gastrointestinal disorders Constipation	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Gastrointestinal disorders Dysphagia	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Nervous system disorders Dysphasia	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Nervous system disorders Facial nerve disorder	0.00% 0/6 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
General disorders Fatigue	66.7% 4/6 • Number of events 4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
General disorders Fever	50.0% 3/6 • Number of events 3 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	50.0% 2/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
General disorders Flu like symptoms	83.3% 5/6 • Number of events 5 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	75.0% 3/4 • Number of events 3 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Gastrointestinal disorders Gastritis	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Gastrointestinal disorders Gastroesophageal reflux disease	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Nervous system disorders Headache	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
General disorders Injection site reaction	100.0% 6/6 • Number of events 6 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	100.0% 4/4 • Number of events 4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Psychiatric disorders Insomnia	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Gastrointestinal disorders Nausea	16.7% 1/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Musculoskeletal and connective tissue disorders Neck pain	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Musculoskeletal and connective tissue disorders Non-cardiac chest pain	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
General disorders Pain	83.3% 5/6 • Number of events 5 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	100.0% 4/4 • Number of events 4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Nervous system disorders Paresthesia	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Reproductive system and breast disorders Pelvic pain	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Reproductive system and breast disorders Perineal pain	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Respiratory, thoracic and mediastinal disorders Pleural effusion	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Nervous system disorders Recurrent laryngeal nerve palsy	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Infections and infestations Upper respiratory infection	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Infections and infestations Urinary tract infection	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Investigations Weight loss	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.
Infections and infestations Wound infection	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 16 months and 6 days.	0.00% 0/4 • Date treatment consent signed to date off study, approximately 16 months and 6 days.