Trial Outcomes & Findings for A Trial For Participants With Ewing's Sarcoma Treated With Vigil in Combination With Irinotecan and Temozolomide (NCT NCT03495921)

Last Updated: 2023-04-26

Results Overview

Progression Free Survival (PFS) is defined as the time from randomization to the event of disease recurrence/progression according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) for target lesions and assessed CT/MRI by local investigator.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

32 participants

Primary outcome timeframe

From date of randomization until the date of first documented progression (assessed up to 3 years).

Results posted on

2023-04-26

Participant Flow

Thirty-two (32) subjects signed consent for the tissue procurement portion of the study. Twenty-seven (27) subjects were not eligible to enroll into the main treatment portion of the study. Five (5) subjects were randomized into the main treatment portion of the study. Group B - crossover to receive 2nd Intervention with Vigil only: One (1) subject in Group B was not eligible to crossover to receive treatment with Vigil and 1 subject from Group B crossed over to receive Vigil.

Participant milestones

Participant milestones
Measure	Group A: Vigil in Combination With Irinotecan and Temozolomide Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.	Group B: Irinotecan and Temozolomide Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.
Main Study STARTED	3	2
Main Study COMPLETED	3	2
Main Study NOT COMPLETED	0	0
Group B Crossover to Vigil Alone STARTED	0	1
Group B Crossover to Vigil Alone COMPLETED	0	1
Group B Crossover to Vigil Alone NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Trial For Participants With Ewing's Sarcoma Treated With Vigil in Combination With Irinotecan and Temozolomide

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: From date of randomization until the date of first documented progression (assessed up to 3 years).

Population: PFS is not adequately assessable for difference between cohorts given only 5 participants were enrolled and received treatment.

Outcome measures

Outcome measures
Measure	Group A: Vigil in Combination With Irinotecan and Temozolomide n=3 Participants Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.	Group B: Irinotecan and Temozolomide n=2 Participants Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.
Progression Free Survival (PFS)	2.8 Months Interval 2.7 to N/A = Not Available. Upper confidence interval could not be calculated as there were insufficient number of participants with event.	9.1 Months Interval 2.8 to N/A = Not Available. Upper confidence interval could not be calculated as there were insufficient number of participants with event.

SECONDARY outcome

Timeframe: From date of randomization until date of death from any cause, whichever came first (assessed up to 3 years).

Population: OS is not adequately assessable for difference between cohorts given only 5 participants were enrolled and received treatment.

OS is defined as time from randomization to death or to the date of last follow-up. The date of last follow-up confirming survival will be used as the censoring date for subjects who are alive and/or do not have a known date of death.

Outcome measures

Outcome measures
Measure	Group A: Vigil in Combination With Irinotecan and Temozolomide n=3 Participants Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.	Group B: Irinotecan and Temozolomide n=2 Participants Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.
Overall Survival (OS)	16.1 Months Interval 14.6 to N/A = Not Available. Upper confidence interval could not be calculated as there were insufficient number of participants with event.	3.3 Months Interval 3.3 to N/A = Not Available. Upper confidence interval could not be calculated as there were insufficient number of participants with event.

SECONDARY outcome

Timeframe: 6 months after treatment with Vigil.

Population: No subjects on trial achieved a partial or complete response, therefore the ORR was not determined.

ORR is defined as the proportion of participants who have prolonged stable disease or a partial or complete response or complete response to therapy according to RECIST 1.1.

Outcome measures

Outcome measures
Measure	Group A: Vigil in Combination With Irinotecan and Temozolomide n=3 Participants Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.	Group B: Irinotecan and Temozolomide n=2 Participants Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.
Overall Response Rate (ORR)	0 Proportion of participants.	0 Proportion of participants.

SECONDARY outcome

Timeframe: From manufacturing start date until 4 weeks post manufacturing for each tissue procurement (assessed up to 17 months).

Population: All enrolled subjects who completed tissue procurement and the tissue was received by Gradalis for Vigil Manufacture. Any subjects whose tissue was not submitted to Gradalis was excluded in the analysis.

Participants were considered eligible for treatment, if the tissue submitted to Gradalis met all criteria, including manufacturing product release criteria.

Outcome measures

Outcome measures
Measure	Group A: Vigil in Combination With Irinotecan and Temozolomide n=30 Participants Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.	Group B: Irinotecan and Temozolomide Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.
Vigil Manufacture Success Rate: Number of Participants Eligible for Treatment on the Main Study.	4 Participants	—

Adverse Events

Group A: Vigil in Combination With Irinotecan and Temozolomide

Serious events: 0 serious events

Other events: 3 other events

Deaths: 2 deaths

Group B: Irinotecan and Temozolomide

Serious events: 1 serious events

Other events: 2 other events

Deaths: 1 deaths

Cross-over to Vigil Alone

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group A: Vigil in Combination With Irinotecan and Temozolomide n=3 participants at risk Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study.	Group B: Irinotecan and Temozolomide n=2 participants at risk Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study.	Cross-over to Vigil Alone n=1 participants at risk Participants assigned to Group B crossed-over to received Vigil monotherapy at a concentration of 1 X 10e6 cells//dose via intradermal injection every 21 days following End of Treatment assessment. Participants received up to 12 doses of Vigil depending upon the quantity of Vigil manufactured.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/3 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.	50.0% 1/2 • Number of events 1 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.	0.00% 0/1 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.	50.0% 1/2 • Number of events 1 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.	0.00% 0/1 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.	50.0% 1/2 • Number of events 1 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.	0.00% 0/1 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/3 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.	50.0% 1/2 • Number of events 1 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.	0.00% 0/1 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.
Respiratory, thoracic and mediastinal disorders Pulmonary Edema	0.00% 0/3 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.	50.0% 1/2 • Number of events 1 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.	0.00% 0/1 • SAEs and Other Adverse Events: following procurement of the subject's tissue for tissue manufacture and for up to 30 days following the last study treatment, a duration of approximately 12 months. All-cause Mortality: from randomization date and until death or protocol termination, up to 3 years. All treated participants.

Other adverse events

Additional Information

Clinical and Regulatory Operations

Gradalis, Inc.

Phone: (214) 442-8100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Group A: Vigil in Combination With Irinotecan and Temozolomide n=3 Participants Participants randomized to Group A received oral temozolomide 100 mg/m\^2 daily (Days 1-5), total dose 500 mg/m\^2/cycle) and oral irinotecan 50 mg/m\^2 daily (Days 1-5, total dose 250 mg/m\^2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.	Group B: Irinotecan and Temozolomide n=2 Participants Participants randomized to Group B received oral temozolomide 100 mg/m\^2 daily (Days 1-5), total dose 500 mg/m\^2/cycle) and oral irinotecan 50 mg/m\^2 daily (Days 1-5, total dose 250 mg/m\^2/cycle). 1 cycle = 21 days Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.	Total n=5 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	3 Participants n=5 Participants	2 Participants n=7 Participants	5 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	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Baseline Performance Status 80	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Baseline Performance Status 100	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants