Trial Outcomes & Findings for PolyPEPI1018 Vaccine and CDx for the Treatment of Metastatic Colorectal Cancer (OBERTO) (NCT NCT03391232)
NCT ID: NCT03391232
Last Updated: 2022-05-26
Results Overview
Occurrence of at least 1 ≥Grade 4 local adverse event (AE) or 1 ≥Grade 3 systemic AE and/or signs/symptoms, lab toxicities, and/or clinical events that is probably or definitely related to study treatment
COMPLETED
PHASE1/PHASE2
11 participants
from 1st vaccination to 21 days after last vaccinations, up to 41 weeks
2022-05-26
Participant Flow
The participants were recruited based on physicians referral at two medical centers between May and Dec 2018. The first subject was enrolled on 3 May 2018 and the last subject was enrolled on 13 Dec 2018.
Of 13 screened participants 11 met the inclusion criteria and were enrolled and treated. One of the two not enrolled subjects were over 75 years (IN01), and the other had the last CT scan over 3 weeks (IN07). All 11 subjects started and completed Part A to get the first dose and 6 of them continued treatment in Part B for additional doses (Amended protocol).
Participant milestones
| Measure |
Single Dose - PolyPEPI1018 CRC Vaccine
The subjects in this group received only one dose of PolyPEPI1018 CRC vaccine and they finished the trial after 12 weeks follow up.
The PolyPEPI1018 CRC vaccine contains 6 synthetic peptides derived from 7 tumor specific antigens (AG), mixed with the adjuvant Montanide™.
|
Multiple Doses - PolyPEPI1018 CRC Vaccine
The subjects received 3 doses of the PolyPEPI1018 CRC vaccine Q12W. The PolyPEPI1018 CRC vaccine contains 6 synthetic peptides derived from 7 tumor specific antigens (AG), mixed with the adjuvant Montanide™.
|
|---|---|---|
|
Part A - First Dose (1-12weeks)
STARTED
|
5
|
6
|
|
Part A - First Dose (1-12weeks)
COMPLETED
|
5
|
6
|
|
Part A - First Dose (1-12weeks)
NOT COMPLETED
|
0
|
0
|
|
Part B - Additional 2 Doses (13-38weeks)
STARTED
|
0
|
6
|
|
Part B - Additional 2 Doses (13-38weeks)
COMPLETED
|
0
|
3
|
|
Part B - Additional 2 Doses (13-38weeks)
NOT COMPLETED
|
0
|
3
|
Reasons for withdrawal
| Measure |
Single Dose - PolyPEPI1018 CRC Vaccine
The subjects in this group received only one dose of PolyPEPI1018 CRC vaccine and they finished the trial after 12 weeks follow up.
The PolyPEPI1018 CRC vaccine contains 6 synthetic peptides derived from 7 tumor specific antigens (AG), mixed with the adjuvant Montanide™.
|
Multiple Doses - PolyPEPI1018 CRC Vaccine
The subjects received 3 doses of the PolyPEPI1018 CRC vaccine Q12W. The PolyPEPI1018 CRC vaccine contains 6 synthetic peptides derived from 7 tumor specific antigens (AG), mixed with the adjuvant Montanide™.
|
|---|---|---|
|
Part B - Additional 2 Doses (13-38weeks)
Physician Decision
|
0
|
1
|
|
Part B - Additional 2 Doses (13-38weeks)
Withdrawal by Subject
|
0
|
2
|
Baseline Characteristics
PolyPEPI1018 Vaccine and CDx for the Treatment of Metastatic Colorectal Cancer (OBERTO)
Baseline characteristics by cohort
| Measure |
Single Dose of PolyPEPI1018 CRC Vaccine
n=5 Participants
The subjects were treated with only one dose PolyPEPI1018 CRC vaccine.
|
Multiple Dose of PolyPEPI1018 CRC Vaccine
n=6 Participants
The subjects received 2 or 3 doses PolyPEPI1018 CRC vaccine.
|
Total
n=11 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.8 years
STANDARD_DEVIATION 5.3 • n=5 Participants
|
47.5 years
STANDARD_DEVIATION 6.0 • n=7 Participants
|
55.4 years
STANDARD_DEVIATION 10.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
1 participants
n=5 Participants
|
6 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
4 participants
n=5 Participants
|
0 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Weight
|
82.6 Kg
STANDARD_DEVIATION 13.2 • n=5 Participants
|
95.7 Kg
STANDARD_DEVIATION 24.9 • n=7 Participants
|
89.7 Kg
STANDARD_DEVIATION 20.6 • n=5 Participants
|
|
Height
|
160.0 cm
STANDARD_DEVIATION 33.7 • n=5 Participants
|
185.9 cm
STANDARD_DEVIATION 9.6 • n=7 Participants
|
174.1 cm
STANDARD_DEVIATION 26.2 • n=5 Participants
|
PRIMARY outcome
Timeframe: from 1st vaccination to 21 days after last vaccinations, up to 41 weeksPopulation: All subjects
Occurrence of at least 1 ≥Grade 4 local adverse event (AE) or 1 ≥Grade 3 systemic AE and/or signs/symptoms, lab toxicities, and/or clinical events that is probably or definitely related to study treatment
Outcome measures
| Measure |
Single Dose of PolyPEPI1018 CRC Vaccine
n=5 Participants
The subjects were treated with only one dose PolyPEPI1018 CRC vaccine.
|
Multiple Dose of PolyPEPI1018 CRC Vaccine
n=6 Participants
The subjects received 2 or 3 doses PolyPEPI1018 CRC vaccine.
|
|---|---|---|
|
Number of Participants With Treatment Related Adverse Events
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Ten of 11 subject had sufficient PBMC samples to evaluate T cell responses
Measured CD4+ and CD8+ T cell responses from each subject for each antigen of the vaccine
Outcome measures
| Measure |
Single Dose of PolyPEPI1018 CRC Vaccine
n=4 Participants
The subjects were treated with only one dose PolyPEPI1018 CRC vaccine.
|
Multiple Dose of PolyPEPI1018 CRC Vaccine
n=6 Participants
The subjects received 2 or 3 doses PolyPEPI1018 CRC vaccine.
|
|---|---|---|
|
Number of Participants Having T Cell Immune Response
CD4+ T cell responses
|
4 Participants
|
6 Participants
|
|
Number of Participants Having T Cell Immune Response
CD8+ T cell responses
|
4 Participants
|
5 Participants
|
|
Number of Participants Having T Cell Immune Response
CD8+ T cell responses against 3 or more AG
|
4 Participants
|
4 Participants
|
|
Number of Participants Having T Cell Immune Response
Booth CD4+ and CD8+ T cell responses
|
4 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: 21 daysPopulation: All subjects
Epitopes restricted to multiple HLA class I alleles (Personal Epitope, PEPI) of a subject were predicted. PEPIs determined for each vaccine antigen can predict the antigen-specific T cell responses for each patient.
Outcome measures
| Measure |
Single Dose of PolyPEPI1018 CRC Vaccine
n=5 Participants
The subjects were treated with only one dose PolyPEPI1018 CRC vaccine.
|
Multiple Dose of PolyPEPI1018 CRC Vaccine
n=6 Participants
The subjects received 2 or 3 doses PolyPEPI1018 CRC vaccine.
|
|---|---|---|
|
Number of Predicted Antigen Specific T Cell Responses Per Patient
|
4.80 predicted PEPIs
Standard Deviation 1.64
|
4.17 predicted PEPIs
Standard Deviation 1.33
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeksPopulation: Full set
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. CT scans were performed at screening and weeks 6,12 after each vaccination. The objective response were based on for each subject's last CT scan evaluation.
Outcome measures
| Measure |
Single Dose of PolyPEPI1018 CRC Vaccine
n=5 Participants
The subjects were treated with only one dose PolyPEPI1018 CRC vaccine.
|
Multiple Dose of PolyPEPI1018 CRC Vaccine
n=6 Participants
The subjects received 2 or 3 doses PolyPEPI1018 CRC vaccine.
|
|---|---|---|
|
Number of Participants With Objective Tumor Responses - Objective Response Rate (RECIST v1.1)
|
1 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeksPopulation: Full set
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD) \<30% increase compare to smallest sum of the longest diameter of target lesions. CT scans were performed at screening and weeks 6,12 after each vaccination. The DCR were counted as the best response (PR or SD) for each subject's during the trial.
Outcome measures
| Measure |
Single Dose of PolyPEPI1018 CRC Vaccine
n=5 Participants
The subjects were treated with only one dose PolyPEPI1018 CRC vaccine.
|
Multiple Dose of PolyPEPI1018 CRC Vaccine
n=6 Participants
The subjects received 2 or 3 doses PolyPEPI1018 CRC vaccine.
|
|---|---|---|
|
Number of Participants With Objective Tumor Responses - Disease Control Rate (Best Overall Response is Partial Response or Stable Disease)
|
4 Participants
|
5 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Last visit, up to 38 weeksPopulation: Only subjects who had tissue-pairs for TIL measurements (4 of 11).
Assessments of TILs was performed using IHC (Immunoscore CR) CD3/CD8 testing on liver biopsy tissue samples obtained from subjects during a time course from baseline until the Last Visit. The CD3+ and CD8+ cell densities were determined in the core tumor and invasive margin using Immunohistochemistry (IHC) staining followed by digital pathology.
Outcome measures
| Measure |
Single Dose of PolyPEPI1018 CRC Vaccine
n=2 Participants
The subjects were treated with only one dose PolyPEPI1018 CRC vaccine.
|
Multiple Dose of PolyPEPI1018 CRC Vaccine
n=2 Participants
The subjects received 2 or 3 doses PolyPEPI1018 CRC vaccine.
|
|---|---|---|
|
Number of Participants Having Induced Recruitment of TILs
|
1 Participants
|
2 Participants
|
Adverse Events
Single Dose of PolyPEPI1018 CRC Vaccine
Multiple Dose of PolyPEPI1018 CRC Vaccine
Serious adverse events
| Measure |
Single Dose of PolyPEPI1018 CRC Vaccine
n=5 participants at risk
The subjects were treated with only one dose PolyPEPI1018 CRC vaccine.
|
Multiple Dose of PolyPEPI1018 CRC Vaccine
n=6 participants at risk
The subjects received 2 or 3 doses PolyPEPI1018 CRC vaccine.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
THROMBOEMBOLIC EVENT (Embolism)
|
0.00%
0/5 • up to 41 weeks
|
16.7%
1/6 • Number of events 1 • up to 41 weeks
|
|
Gastrointestinal disorders
ABDOMINAL PAIN (Abdominal pain)
|
0.00%
0/5 • up to 41 weeks
|
16.7%
1/6 • Number of events 1 • up to 41 weeks
|
|
Gastrointestinal disorders
BOWEL OBSTRUCTION (Intestinal obstruction)
|
0.00%
0/5 • up to 41 weeks
|
16.7%
1/6 • Number of events 1 • up to 41 weeks
|
|
Nervous system disorders
NON-INFECTIOUS ACUTE ENCEPHALITIS (Noninfective encephalitis)
|
20.0%
1/5 • Number of events 1 • up to 41 weeks
|
0.00%
0/6 • up to 41 weeks
|
Other adverse events
| Measure |
Single Dose of PolyPEPI1018 CRC Vaccine
n=5 participants at risk
The subjects were treated with only one dose PolyPEPI1018 CRC vaccine.
|
Multiple Dose of PolyPEPI1018 CRC Vaccine
n=6 participants at risk
The subjects received 2 or 3 doses PolyPEPI1018 CRC vaccine.
|
|---|---|---|
|
General disorders
INJECTION SITE REACTION-SOME SUBCUTANEOUS NODULARITY
|
20.0%
1/5 • Number of events 1 • up to 41 weeks
|
50.0%
3/6 • Number of events 4 • up to 41 weeks
|
|
Musculoskeletal and connective tissue disorders
MUSCLE DISORDERS
|
0.00%
0/5 • up to 41 weeks
|
16.7%
1/6 • Number of events 2 • up to 41 weeks
|
|
Nervous system disorders
NEUROLOGICAL DISRORDERS NEC
|
20.0%
1/5 • Number of events 1 • up to 41 weeks
|
0.00%
0/6 • up to 41 weeks
|
|
Blood and lymphatic system disorders
ANAEMIAS NONHAEMOLYTIC AND MARROW DEPRESSION
|
0.00%
0/5 • up to 41 weeks
|
16.7%
1/6 • Number of events 1 • up to 41 weeks
|
|
Gastrointestinal disorders
GASTROINTESTINAL MOTILITY AND DEFAECATION CONDITIONS
|
0.00%
0/5 • up to 41 weeks
|
16.7%
1/6 • Number of events 1 • up to 41 weeks
|
|
Gastrointestinal disorders
GASTROINTESTINAL SIGNS AND SYMPTOMS
|
0.00%
0/5 • up to 41 weeks
|
16.7%
1/6 • Number of events 1 • up to 41 weeks
|
|
Musculoskeletal and connective tissue disorders
JOINT DISORDERS
|
0.00%
0/5 • up to 41 weeks
|
16.7%
1/6 • Number of events 1 • up to 41 weeks
|
|
Vascular disorders
EMBOLISM AND THROMBOSIS
|
0.00%
0/5 • up to 41 weeks
|
16.7%
1/6 • Number of events 1 • up to 41 weeks
|
|
General disorders
GENERAL SYSTEM DISORDERS NEC
|
0.00%
0/5 • up to 41 weeks
|
16.7%
1/6 • Number of events 1 • up to 41 weeks
|
|
Skin and subcutaneous tissue disorders
EPIDERMAL AND DERMAL CONDITIONS
|
0.00%
0/5 • up to 41 weeks
|
16.7%
1/6 • Number of events 1 • up to 41 weeks
|
|
Nervous system disorders
CENTRAL NERVOUS SYSTEM INFECTIONS AND INFLAMMATIONS
|
20.0%
1/5 • Number of events 1 • up to 41 weeks
|
0.00%
0/6 • up to 41 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place