Trial Outcomes & Findings for Optimizing Antitumor Immunity Using Plasmid Electroporation, Pembrolizumab, and Epacadostat (NCT NCT03823131)
NCT ID: NCT03823131
Last Updated: 2023-05-09
Results Overview
The best overall response (BORR) is defined as the best response recorded from the start of treatment until disease progression/recurrence. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The combined percentage of participants relative to the total size of the All Treated Subjects population having a demonstrated best response of CR or PR, with a confirmatory scan will be reported.
TERMINATED
PHASE2
14 participants
Up to 36 months
2023-05-09
Participant Flow
Enrollment in Arm A was terminated earlier than expected. Arms B and Arm C were never opened for enrollment.
Participant milestones
| Measure |
Arm A: Tavo-EP, Pembrolizumab, Epacadostat
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
|
Arm B: Tavo-EP, Pembrolizumab
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks.
|
Arm C: Tavo-EP, Pembrolizumab, CORVax
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30-minute IV infusion at a dose of 200 mg every 3 weeks. CORVax will be administered at a total dose of 0.2 mg of (S) protein plasmid in 120 microliter (uL) per lesion intratumorally into a maximum of 4 lesions of at least 0.3 mm in diameter for a total plasmid dose of 0.8 mg on treatment days 1 and 29 of cycle 1 followed by electroporation of the plasmid solution in infiltrated regions. On days when both tavo and CORVax is administered to the same lesions, tavo and CORVax will each be injected into the lesion followed by electroporation.
|
|---|---|---|---|
|
Overall Study
STARTED
|
14
|
0
|
0
|
|
Overall Study
COMPLETED
|
14
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Optimizing Antitumor Immunity Using Plasmid Electroporation, Pembrolizumab, and Epacadostat
Baseline characteristics by cohort
| Measure |
Arm A: Tavo-EP, Pembrolizumab, Epacadostat
n=14 Participants
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
|
Arm B: Tavo-EP, Pembrolizumab
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks.
|
Arm C: Tavo-EP, Pembrolizumab, CORVax
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30-minute IV infusion at a dose of 200 mg every 3 weeks. CORVax will be administered at a total dose of 0.2 mg of (S) protein plasmid in 120 microliter (uL) per lesion intratumorally into a maximum of 4 lesions of at least 0.3 mm in diameter for a total plasmid dose of 0.8 mg on treatment days 1 and 29 of cycle 1 followed by electroporation of the plasmid solution in infiltrated regions. On days when both tavo and CORVax is administered to the same lesions, tavo and CORVax will each be injected into the lesion followed by electroporation.
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
30-39 years old
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Age, Customized
40-49 years old
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
|
Age, Customized
50-59 years old
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
|
Age, Customized
60-69 years old
|
4 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
|
Age, Customized
70-79 years old
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
6 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
14 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
14 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Up to 36 monthsThe best overall response (BORR) is defined as the best response recorded from the start of treatment until disease progression/recurrence. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The combined percentage of participants relative to the total size of the All Treated Subjects population having a demonstrated best response of CR or PR, with a confirmatory scan will be reported.
Outcome measures
| Measure |
Arm A: Tavo-EP, Pembrolizumab, Epacadostat
n=14 Participants
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
|
|---|---|
|
Best Overall Response Rate
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 36 monthsProgression-free survival will be calculated as number of months from the first dosing date until the date of disease progression (i.e the date of the tumor imaging following baseline per central imaging assessment by a radiologist) or death from any cause. Per RECIST version 1.1, Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Participants who do not have documented disease progression will have their months of PFS censored on the last date of tumor assessment, or death, whichever comes first. Censoring data on date of last tumor imaging to calculate the median PFS will not occur until the overall survival data collection for all participants has been completed.
Outcome measures
| Measure |
Arm A: Tavo-EP, Pembrolizumab, Epacadostat
n=14 Participants
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
|
|---|---|
|
Median Months of Progression-Free Survival (PFS)
|
1.76 months
Interval 0.89 to 5.26
|
SECONDARY outcome
Timeframe: Up to 36 monthsOverall survival (OS) is defined as the number of months from the date of enrollment until the date of death regardless of cause, last date of follow-up, or date of study closure (if still alive), whichever comes first. Median months of overall participant survival will be reported using descriptive statistics.
Outcome measures
| Measure |
Arm A: Tavo-EP, Pembrolizumab, Epacadostat
n=14 Participants
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
|
|---|---|
|
Median Overall Survival (OS)
|
11.6 months
Interval 1.02 to 36.0
|
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: No participants achieved an objective response, therefore a time to response could not be calculated.
Time to response is defined as the number of days from the date of enrollment to the date of the first documented response of CR or PR. The median time to response will be summarized by descriptive statistics.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 36 monthsThe disease control rate is defined as the best response recorded from the start of treatment including stable disease, until disease progression/recurrence (PD). Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The proportion of participants relative to the total size of the All Treated Subjects population having a demonstrated response of CR, PR, or SD, with a confirmatory scan will be reported.
Outcome measures
| Measure |
Arm A: Tavo-EP, Pembrolizumab, Epacadostat
n=14 Participants
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
|
|---|---|
|
Disease Control Rate (DCR)
Complete Response
|
0 proportion of participants
|
|
Disease Control Rate (DCR)
Partial Response
|
0 proportion of participants
|
|
Disease Control Rate (DCR)
Stable Disease
|
0.21 proportion of participants
|
SECONDARY outcome
Timeframe: Up to 36 monthsClinical benefit rate (CBR) is defined as the percentage of participants who achieved a best overall response of CR, PR and SD with a duration of response lasting at least 6 months or longer.
Outcome measures
| Measure |
Arm A: Tavo-EP, Pembrolizumab, Epacadostat
n=14 Participants
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
|
|---|---|
|
Clinical Benefit Rate (CBR)
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: No participants achieved an objective response, therefore a duration of response could not be calculated.
The duration of response (DOR) will be calculated for participants who achieved a best overall response of CR or PR and calculated as the number of days from the date when CR or PR is first confirmed to the date of progression or death. Participants who do not have a documented progression or death will be censored on the last date of tumor assessment. The median DOR and 95% confidence intervals will be reported.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 36 monthsThe proportion of participants with reported treatment-related adverse events, which are adverse events defined as having an attribution of possible, probable, or definite according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4 will be reported.
Outcome measures
| Measure |
Arm A: Tavo-EP, Pembrolizumab, Epacadostat
n=14 Participants
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
|
|---|---|
|
Proportion of Participants With Reported Treatment-related Adverse Events (AEs)
|
0.64 proportion of participants
|
Adverse Events
Arm A: Tavo-EP, Pembrolizumab, Epacadostat
Serious adverse events
| Measure |
Arm A: Tavo-EP, Pembrolizumab, Epacadostat
n=14 participants at risk
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
|
|---|---|
|
General disorders
Edema, Face
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Infections and infestations
Sepsis
|
14.3%
2/14 • Number of events 2 • Up to 36 months
|
|
Psychiatric disorders
Psychiatric disorders - Other
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders, Other
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
Other adverse events
| Measure |
Arm A: Tavo-EP, Pembrolizumab, Epacadostat
n=14 participants at risk
Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
14.3%
2/14 • Number of events 2 • Up to 36 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
14.3%
2/14 • Number of events 2 • Up to 36 months
|
|
General disorders
Fatigue
|
14.3%
2/14 • Number of events 3 • Up to 36 months
|
|
General disorders
Fever
|
14.3%
2/14 • Number of events 2 • Up to 36 months
|
|
General disorders
Injection site reaction
|
14.3%
2/14 • Number of events 2 • Up to 36 months
|
|
General disorders
Chills
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
General disorders
Non-cardiac chest pain
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
General disorders
Pain
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor Pain
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Investigations
Weight Loss
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Injury, poisoning and procedural complications
Tracheostomy site bleeding
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Immune system disorders
Allergic Reaction
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Eye disorders
Blurred Vision
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Ear and labyrinth disorders
External ear inflammation
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Ear and labyrinth disorders
External ear pain
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Vascular disorders
Lymphedema
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Psychiatric disorders
Insomnia
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Infections and infestations
Sinusitis
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
14.3%
2/14 • Number of events 3 • Up to 36 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Nervous system disorders
Dizziness
|
14.3%
2/14 • Number of events 2 • Up to 36 months
|
|
Nervous system disorders
Headache
|
14.3%
2/14 • Number of events 2 • Up to 36 months
|
|
Nervous system disorders
Dysgeusia
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Nervous system disorders
Syncope
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
7.1%
1/14 • Number of events 2 • Up to 36 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.3%
2/14 • Number of events 2 • Up to 36 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
21.4%
3/14 • Number of events 3 • Up to 36 months
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
1/14 • Number of events 2 • Up to 36 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Gastrointestinal disorders
Dry Mouth
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Gastrointestinal disorders
Constipation
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Gastrointestinal disorders
Abdominal distension
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Gastrointestinal disorders
Nasuea
|
14.3%
2/14 • Number of events 3 • Up to 36 months
|
|
Gastrointestinal disorders
Dysphagia
|
14.3%
2/14 • Number of events 2 • Up to 36 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
14.3%
2/14 • Number of events 2 • Up to 36 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
28.6%
4/14 • Number of events 4 • Up to 36 months
|
|
Infections and infestations
Sepsis
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
General disorders
Edema face
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
General disorders
Localized edema
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
General disorders
Gait Disturbance
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
Nervous system disorders
Anosmia
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
|
General disorders
General disorders and administration site conditions - Other
|
7.1%
1/14 • Number of events 1 • Up to 36 months
|
Additional Information
Dr Chase Heaton, MD
University of California, San Francisco
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place