Trial Outcomes & Findings for Post-Marketing Assessment of Immunogenicity and Safety of Unituxin® in High-Risk Neuroblastoma Patients (NCT NCT02693171)

Last Updated: 2019-08-05

Results Overview

Seven blood samples were collected at the following time points for the evaluation of HACA levels: * Course 1- Prior to the first Unituxin infusion * Course 2- Prior to the first Unituxin infusion * Course 3- Prior to the first Unituxin infusion * Course 4- Prior to the first Unituxin infusion * Course 5- Prior to the first Unituxin infusion * Course 6- Prior to the first dose of 13-cis-retinoic acid (RA) * Study termination (approximately 2 weeks following the final 13-cis-retinoic acid dose)

Recruitment status

TERMINATED

Target enrollment

13 participants

Primary outcome timeframe

Approximately 6 months

Results posted on

2019-08-05

Participant Flow

Participant milestones

Participant milestones
Measure	Dinutuximab Administered for 5 Cycles High-risk neuroblastoma patient treated with Unituxin as standard of care Dinutuximab: Unituxin was administered along with cytokines according to the prescribing information
Overall Study STARTED	12
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Dinutuximab Administered for 5 Cycles High-risk neuroblastoma patient treated with Unituxin as standard of care Dinutuximab: Unituxin was administered along with cytokines according to the prescribing information
Overall Study Adverse Event	1
Overall Study Discontinuation of Study by Sponsor	8

Baseline Characteristics

Post-Marketing Assessment of Immunogenicity and Safety of Unituxin® in High-Risk Neuroblastoma Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dinutuximab Administered for 5 Cycles n=12 Participants High-risk neuroblastoma patient treated with Unituxin as standard of care Dinutuximab: Unituxin was administered along with cytokines according to the prescribing information
Age, Continuous	2.3 years STANDARD_DEVIATION 1.37 • n=5 Participants
Age, Customized Age at Diagnosis	1.9 years STANDARD_DEVIATION 1.24 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants
Time since Diagnosis	0.8 years STANDARD_DEVIATION 0.62 • n=5 Participants
Treatment of Neuroblastoma Induction chemotherapy treatment	12 Participants n=5 Participants
Treatment of Neuroblastoma Cancer-related surgery	10 Participants n=5 Participants
Treatment of Neuroblastoma Single stem cell transplant	3 Participants n=5 Participants
Treatment of Neuroblastoma Tandem stem cell transplant	9 Participants n=5 Participants
Treatment of Neuroblastoma Radiotherapy treatment	11 Participants n=5 Participants
Treatment of Neuroblastoma Other cancer-related treatment	1 Participants n=5 Participants
Pre-Autologous Stem Cell Transplantation (ASCT) Response Complete response (CR)	3 Participants n=5 Participants
Pre-Autologous Stem Cell Transplantation (ASCT) Response Very good partial response (VGPR)	6 Participants n=5 Participants
Pre-Autologous Stem Cell Transplantation (ASCT) Response Partial response (PR)	3 Participants n=5 Participants
Pre-Autologous Stem Cell Transplantation (ASCT) Response Mixed response (MR)	0 Participants n=5 Participants
Pre-Autologous Stem Cell Transplantation (ASCT) Response No response (NR)	0 Participants n=5 Participants
Pre-Autologous Stem Cell Transplantation (ASCT) Response Progressive disease (PD)	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 6 months

Population: Outcome measure data were not collected. Sponsor was required to run this Phase 4 study for EU marketing approval. However, Sponsor terminated the study 15 Dec 2016 and application withdrawn (accepted by European Commission 20 Mar 2017).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 6 months

Population: Outcome measure data were not collected. Safety data from the 12 subjects dosed prior to study termination were collected and summary level data were reported (eg, total number of subjects affected and total number of events for dinutuximab-treated subjects). Please refer to the adverse event tables for results.

The incidence of targeted immune-related adverse events (AEs) during treatment with dinutuximab combination therapy in high-risk neuroblastoma subjects were summarized and listed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 6 months

Incidence of neutralizing antibody (NAb) in patients with human anti-chimeric antibody (HACA) positive samples was summarized and listed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 6 months

Ten blood samples were collected at the following time points for the evaluation of dinutuximab plasma concentrations: * Course 1- Prior to the first Unituxin infusion * Course 2- Prior to the first Unituxin infusion * Course 3- Prior to the first Unituxin infusion * Course 4- Prior to the first Unituxin infusion * Course 5- Prior to the first Unituxin infusion * Course 6- Prior to the first dose of 13-cis-retinoic acid (RA) * Study termination (approximately 2 weeks following the final 13-cis-retinoic acid dose). An additional 3 blood samples were obtained for the evaluation of dinutuximab plasma concentrations. Each of these blood samples was obtained immediately following the fourth dinutuximab infusion in Courses 1, 3, and 5.

Outcome measures

Outcome data not reported

Adverse Events

Dinutuximab Administered for 5 Cycles

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Dinutuximab Administered for 5 Cycles n=12 participants at risk High-risk neuroblastoma patient treated with Unituxin as standard of care Dinutuximab: Unituxin was administered along with cytokines according to the prescribing information
Skin and subcutaneous tissue disorders Pruritus	50.0% 6/12 • Number of events 10 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Skin and subcutaneous tissue disorders Urticaria	41.7% 5/12 • Number of events 8 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Skin and subcutaneous tissue disorders Drug eruption	33.3% 4/12 • Number of events 4 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Skin and subcutaneous tissue disorders Angioedema	8.3% 1/12 • Number of events 2 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Skin and subcutaneous tissue disorders Rash	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Cardiac disorders Tachycardia	66.7% 8/12 • Number of events 15 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
General disorders Pyrexia	66.7% 8/12 • Number of events 20 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
General disorders Adverse drug reaction	8.3% 1/12 • Number of events 2 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
General disorders Face oedema	8.3% 1/12 • Number of events 4 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
General disorders Oedema	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Respiratory, thoracic and mediastinal disorders Tachypnoea	50.0% 6/12 • Number of events 6 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Respiratory, thoracic and mediastinal disorders Allergic cough	33.3% 4/12 • Number of events 6 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 3/12 • Number of events 4 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Respiratory, thoracic and mediastinal disorders Stridor	16.7% 2/12 • Number of events 3 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 1/12 • Number of events 3 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Respiratory, thoracic and mediastinal disorders Hypoxia	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Respiratory, thoracic and mediastinal disorders Wheezing	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Vascular disorders Hypotension	50.0% 6/12 • Number of events 10 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Vascular disorders Capillary leak syndrome	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Gastrointestinal disorders Abdominal pain	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Gastrointestinal disorders Lip swelling	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Gastrointestinal disorders Vomiting	8.3% 1/12 • Number of events 2 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Investigations Alanine aminotransferase increased	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Investigations Platelet count decreased	16.7% 2/12 • Number of events 15 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Immune system disorders Anaphylactic reaction	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Immune system disorders Drug hypersensitivity	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Blood and lymphatic system disorders Thrombocytopenia	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.
Eye disorders Mydriasis	8.3% 1/12 • Number of events 1 • The Treatment Phase of the study lasted on average approximately 180 days. From Screening until the completion of study termination assessments, subjects participated in the study for approximately 220 days. However, the Sponsor terminated Study DIV-NB-401 on 15 December 2016; all safety data were collected for each subject from screening until the subject's last scheduled visit.

Additional Information

Odette Jordan, MD, PMP

United Therapeutics Corp.

Phone: 919-425-5606

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institution and/or Principal Investigator agree not to publish or publicly present any interim results of the Study without the prior written consent of Sponsor, not to be unreasonably withheld or delayed. Institution and/or Principal Investigator further agree to provide Sponsor with drafts of any such publication or presentation for review and approval no less than 30 days prior to submission for publication or the date of public presentation.
Publication restrictions are in place

Restriction type: OTHER