Trial Outcomes & Findings for Phase II Study of MEDI4736 Monotherapy in Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (NCT NCT02207530)
NCT ID: NCT02207530
Last Updated: 2020-09-29
Results Overview
Objective response rate (per RECIST 1.1 as assessed by blinded independent central review \[BICR\]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR. Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1. criteria are: Complete response \[CR\] = disappearance of all target lesions since baseline; and partial response \[PR\] = at least a 30% decrease in the sum of the diameters of target lesions.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
112 participants
Primary outcome timeframe
12 months
Results posted on
2020-09-29
Participant Flow
110 sites in 14 countries enrolled and screened patients. The study was conducted and managed by PRA, a contract research organization.
Participant milestones
| Measure |
MEDI4736 10 mg/kg
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Overall Study
STARTED
|
112
|
|
Overall Study
COMPLETED
|
21
|
|
Overall Study
NOT COMPLETED
|
91
|
Reasons for withdrawal
| Measure |
MEDI4736 10 mg/kg
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Overall Study
Worsening condition under investigation
|
78
|
|
Overall Study
Patient decision to stop study treatment
|
5
|
|
Overall Study
Adverse Event
|
8
|
Baseline Characteristics
Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
Baseline characteristics by cohort
| Measure |
MEDI4736 10 mg/kg
n=112 Participants
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Age, Categorical
Between 18 and 65 years
|
83 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Age, Categorical
>=65 years
|
29 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Age, Continuous
|
60.0 Years
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Sex: Female, Male
Female
|
32 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Sex: Female, Male
Male
|
80 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
109 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Race (NIH/OMB)
White
|
100 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Smoking/ Nicotine status
>10 Pack years
|
49 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Smoking/ Nicotine status
<=10 pack years
|
53 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Smoking/ Nicotine status
Unknown/ Not reported
|
10 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Nicotine Use
Current
|
10 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Nicotine Use
Former
|
59 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
Nicotine Use
Never
|
43 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
HPV status
Positive
|
34 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
HPV status
Negative
|
65 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
HPV status
Unknown/ Not reported
|
3 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
WHO/ECOG performance status
(0) Normal activity
|
34 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
WHO/ECOG performance status
(1) Restricted activity
|
77 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
|
WHO/ECOG performance status
Missing
|
1 Participants
n=39 Participants • Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease at baseline according to BICR
Objective response rate (per RECIST 1.1 as assessed by blinded independent central review \[BICR\]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR. Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1. criteria are: Complete response \[CR\] = disappearance of all target lesions since baseline; and partial response \[PR\] = at least a 30% decrease in the sum of the diameters of target lesions.
Outcome measures
| Measure |
MEDI4736 10 mg/kg
n=111 Participants
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Objective Response Rate (ORR)
Smoking/nicotine status >10 pack years
|
14.6 % of participants
Interval 6.07 to 27.76
|
|
Objective Response Rate (ORR)
Smoking/nicotine status <=10 pack years
|
18.9 % of participants
Interval 9.44 to 31.97
|
|
Objective Response Rate (ORR)
Smoking/nicotine status - Missing
|
10.0 % of participants
Only 1 patient in this category with a response
|
|
Objective Response Rate (ORR)
Substance user-Current
|
11.1 % of participants
Interval 0.28 to 48.25
|
|
Objective Response Rate (ORR)
Substance user-Former
|
15.3 % of participants
Interval 7.22 to 26.99
|
|
Objective Response Rate (ORR)
Substance user-Never
|
18.6 % of participants
Interval 8.39 to 33.4
|
|
Objective Response Rate (ORR)
HPV status-Positive
|
29.4 % of participants
Interval 15.1 to 47.48
|
|
Objective Response Rate (ORR)
HPV status-Negative
|
10.9 % of participants
Interval 4.51 to 21.25
|
|
Objective Response Rate (ORR)
HPV status-Missing
|
7.7 % of participants
Only 1 patient in this category with a response
|
|
Objective Response Rate (ORR)
Overall
|
16.2 % of participants
Interval 9.9 to 24.41
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Evaluable analysis set - included all patients who received at least one dose of study treatment who had a baseline tumor assessment and had measurable disease at baseline according to BICR.
Best objective response based on BICR assessments according to RECIST v1.1. Response required confirmation after 4 weeks. Unconfirmed complete (CR) or partial response (PR) refers to CR or PR achieved but either no confirmation assessment was performed or a confirmation assessment was performed but response was not confirmed.
Outcome measures
| Measure |
MEDI4736 10 mg/kg
n=111 Participants
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Best Objective Response
Response-Total
|
16.2 % of participants
|
|
Best Objective Response
Response-Partial response (PR)
|
15.3 % of participants
|
|
Best Objective Response
Response-Complete response (CR)
|
0.9 % of participants
|
|
Best Objective Response
Non-response (NR)-Total
|
83.8 % of participants
|
|
Best Objective Response
NR-Stable disease (SD)≥8 weeks-Total
|
9.0 % of participants
|
|
Best Objective Response
NR-SD≥8 weeks-Unconfirmed CR or PR
|
2.7 % of participants
|
|
Best Objective Response
NR-Stable disease (SD) ≥8 weeks-SD
|
6.3 % of participants
|
|
Best Objective Response
NR-Progression-Total
|
52.3 % of participants
|
|
Best Objective Response
NR-Progression-RECIST 1.1 progression
|
25.2 % of participants
|
|
Best Objective Response
NR-Progression-Death
|
27.0 % of participants
|
|
Best Objective Response
NR-Not evaluable-Total
|
22.5 % of participants
|
|
Best Objective Response
NR-Not evaluable-SD<8 weeks
|
19.8 % of participants
|
|
Best Objective Response
NR-Not evaluable-Incomplete post-baseline tests
|
2.7 % of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Evaluable analysis set - included all patients who received at least one dose of study treatment who had a baseline tumor assessment and had measurable disease at baseline according to BICR.
Participants remaining in response - based on BICR assessments according to RECIST v1.1. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
Outcome measures
| Measure |
MEDI4736 10 mg/kg
n=18 Participants
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Duration of Response- Participants Remaining in Response
Ongoing response
|
55.6 % of participants
|
|
Duration of Response- Participants Remaining in Response
Remaining in response-3 months
|
100 % of participants
|
|
Duration of Response- Participants Remaining in Response
Remaining in response-6 months
|
76.5 % of participants
|
|
Duration of Response- Participants Remaining in Response
Remaining in response-9 months
|
61.8 % of participants
|
|
Duration of Response- Participants Remaining in Response
Remaining in response-12 months
|
37.1 % of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Evaluable analysis set - included all patients who received at least one dose of study treatment who had a baseline tumor assessment and had measurable disease at baseline according to BICR.
Duration of objective response in patients with objective response based on BICR assessments according to RECIST v1.1. Duration of response was the time from the first documentation of complete or partial response until the date of progression (which was subsequently confirmed), death, or the last evaluable RECIST assessment for patients that did not progress. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
Outcome measures
| Measure |
MEDI4736 10 mg/kg
n=18 Participants
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Duration of Response
No. progressed or died within 12 months
|
6 Participants
|
|
Duration of Response
No. progressed or died after 12 months
|
2 Participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Evaluable analysis set - included all patients who received at least one dose of study treatment who had a baseline tumor assessment and had measurable disease at baseline according to BICR.
Time to onset of response in patients with objective response based on BICR assessments according to RECIST 1.1
Outcome measures
| Measure |
MEDI4736 10 mg/kg
n=18 Participants
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Time to Onset of Response From First Dose
|
2.00 Months
Interval 1.64 to 9.2
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Evaluable analysis set - included all patients who received at least one dose of study treatment who had a baseline tumor assessment and had measurable disease at baseline according to BICR.
Disease control (DCR) at 6 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD): * Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following the start of study treatment. * Method 2: Patients who had a best objective response of CR or PR within 24 weeks or had demonstrated SD for a minimum interval of 16 weeks following the start of study treatment.
Outcome measures
| Measure |
MEDI4736 10 mg/kg
n=111 Participants
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Disease Control at 6 Months
METHOD 1: Disease control at 6 months
|
23.4 % of participants
|
|
Disease Control at 6 Months
METHOD 1: No disease control at 6 months
|
76.6 % of participants
|
|
Disease Control at 6 Months
METHOD 1: No disease control:Not evaluable/missing
|
27.0 % of participants
|
|
Disease Control at 6 Months
METHOD 2: Disease control at 6 months
|
33.3 % of participants
|
|
Disease Control at 6 Months
METHOD 2: No disease control at 6 months
|
66.7 % of participants
|
|
Disease Control at 6 Months
METHOD 2: No disease control:Not evaluable/missing
|
27.0 % of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
Progression status based on BICR assessments according to RECIST v1.1 at time of PFS analysis. Progression was defined as the time from the date of first dose until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression.
Outcome measures
| Measure |
MEDI4736 10 mg/kg
n=112 Participants
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Progression-free Survival
No progression
|
17.0 % of participants
|
|
Progression-free Survival
No progression + under follow-up
|
12.5 % of participants
|
|
Progression-free Survival
Progression-Total
|
83.0 % of participants
|
|
Progression-free Survival
RECIST 1.1 progression
|
50.0 % of participants
|
|
Progression-free Survival
Death in absence of RECIST 1.1 progression
|
33.0 % of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
Survival status at time of overall survival analysis. 'Still in survival follow-up' includes patients known to be alive at data cut-off. 'Terminated prior to death' includes patients with unknown survival status, or who were lost to follow-up.
Outcome measures
| Measure |
MEDI4736 10 mg/kg
n=112 Participants
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Overall Survival (OS)
Voluntary discontinuation by subject
|
6.3 % of participants
|
|
Overall Survival (OS)
Death
|
69.6 % of participants
|
|
Overall Survival (OS)
Still in survival follow-up
|
24.1 % of participants
|
|
Overall Survival (OS)
Terminated prior to death
|
6.3 % of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Full analysis set - included all treated patients who had a baseline tumor assessment and had measurable disease at baseline according to the Investigator site assessment.
Improvement in quality of life was assessed using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires: * The impact of treatment on Health-Related Quality of Life, functioning, and symptoms was evaluated using the EORTC QLQ-C30 v3. * Head and neck cancer-specific symptoms were evaluated using the EORTC QLQ-H\&N35. Function or global health status/quality of life improvement was defined as patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (an increase from baseline score ≥10). Symptom improvement was defined as 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10). Scale improvement was defined as patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10).
Outcome measures
| Measure |
MEDI4736 10 mg/kg
n=112 Participants
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Quality of Life
EORTC QLQ-C30 Function-Physical
|
17.1 % of participants
Interval 10.1 to 27.6
|
|
Quality of Life
EORTC QLQ-C30 Function-Role
|
22.9 % of participants
Interval 14.6 to 34.0
|
|
Quality of Life
EORTC QLQ-C30 Function-Cognitive
|
21.0 % of participants
Interval 12.7 to 32.6
|
|
Quality of Life
EORTC QLQ-C30 Function-Emotional
|
15.9 % of participants
Interval 9.1 to 26.3
|
|
Quality of Life
EORTC QLQ-C30 Function-Social
|
34.7 % of participants
Interval 24.9 to 45.9
|
|
Quality of Life
EORTC QLQ-C30 Symptom-Fatigue
|
21.3 % of participants
Interval 14.1 to 31.0
|
|
Quality of Life
EORTC QLQ-C30 Symptom-Pain
|
26.8 % of participants
Interval 18.4 to 37.3
|
|
Quality of Life
EORTC QLQ-C30 Symptom-Nausea/vomiting
|
32.3 % of participants
Interval 18.6 to 49.9
|
|
Quality of Life
EORTC QLQ-C30 Global health status/QoL
|
13.5 % of participants
Interval 8.1 to 21.8
|
|
Quality of Life
EORTC QLQ-H&N35 Scale-Pain in the mouth
|
24.6 % of participants
Interval 16.0 to 36.0
|
|
Quality of Life
EORTC QLQ-H&N35 Scale-Swallowing
|
19.4 % of participants
Interval 11.4 to 30.9
|
|
Quality of Life
EORTC QLQ-H&N35 Scale-Senses
|
34.3 % of participants
Interval 24.1 to 46.3
|
|
Quality of Life
EORTC QLQ-H&N35 Scale-Speech
|
28.4 % of participants
Interval 19.7 to 39.0
|
|
Quality of Life
EORTC QLQ-H&N35 Scale-Social eating
|
22.4 % of participants
Interval 14.1 to 33.7
|
|
Quality of Life
EORTC QLQ-H&N35 Scale-Social contact
|
17.2 % of participants
Interval 9.6 to 28.9
|
|
Quality of Life
EORTC QLQ-H&N35 Scale-Sexuality
|
25.7 % of participants
Interval 17.1 to 36.7
|
Adverse Events
MEDI4736 10 mg/kg
Serious events: 43 serious events
Other events: 93 other events
Deaths: 78 deaths
Serious adverse events
| Measure |
MEDI4736 10 mg/kg
n=112 participants at risk
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Cardiac disorders
Atrial fibrillation
|
1.8%
2/112 • Number of events 2 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Cardiac disorders
Cardiac arrest
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Cardiac disorders
Cardiac failure
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Endocrine disorders
Hypercalcaemia of malignancy
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Constipation
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Dysphagia
|
1.8%
2/112 • Number of events 2 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Mouth haemorrhage
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Oesophageal haemorrhage
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Pneumatosis intestinalis
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
General disorders
Chest pain
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
General disorders
Fatigue
|
2.7%
3/112 • Number of events 4 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
General disorders
Localised oedema
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Hepatobiliary disorders
Hepatitis
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Infections and infestations
Abscess neck
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Infections and infestations
Device related infection
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Infections and infestations
Gangrene
|
0.89%
1/112 • Number of events 3 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Infections and infestations
Gastrointestinal infection
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Infections and infestations
Pneumonia
|
3.6%
4/112 • Number of events 5 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Infections and infestations
Pulmonary sepsis
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Infections and infestations
Septic shock
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Infections and infestations
Wound infection
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Injury, poisoning and procedural complications
Fall
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Injury, poisoning and procedural complications
Gastrostomy failure
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Injury, poisoning and procedural complications
Wound haemorrhage
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Investigations
Alanine aminotransferase increased
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Investigations
Aspartate aminotransferase increased
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Investigations
Blood bilirubin increased
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Metabolism and nutrition disorders
Dehydration
|
1.8%
2/112 • Number of events 2 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
1.8%
2/112 • Number of events 2 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.89%
1/112 • Number of events 2 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Nervous system disorders
Cerebral infarction
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Nervous system disorders
Epilepsy
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Nervous system disorders
Nerve compression
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Nervous system disorders
Seizure
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Nervous system disorders
Syncope
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Nervous system disorders
Vascular encephalopathy
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Psychiatric disorders
Confusional state
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Renal and urinary disorders
Nephritis
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopneumopathy
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.8%
2/112 • Number of events 2 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Lung cyst
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.8%
2/112 • Number of events 3 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.8%
2/112 • Number of events 2 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
1.8%
2/112 • Number of events 2 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Vascular disorders
Haemorrhage
|
0.89%
1/112 • Number of events 2 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Vascular disorders
Superior vena cava syndrome
|
0.89%
1/112 • Number of events 1 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
Other adverse events
| Measure |
MEDI4736 10 mg/kg
n=112 participants at risk
MEDI4736 monotherapy: Durvalumab was provided at a dose of 10 mg/kg using an intravenous solution every 2 weeks until 12 months, disease progression, toxicity, or patient decision to stop therapy
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
16.1%
18/112 • Number of events 19 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Endocrine disorders
Hypothyroidism
|
13.4%
15/112 • Number of events 15 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Constipation
|
19.6%
22/112 • Number of events 27 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Diarrhoea
|
14.3%
16/112 • Number of events 28 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Dysphagia
|
9.8%
11/112 • Number of events 11 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Nausea
|
19.6%
22/112 • Number of events 28 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Gastrointestinal disorders
Vomiting
|
11.6%
13/112 • Number of events 19 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
General disorders
Asthenia
|
15.2%
17/112 • Number of events 18 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
General disorders
Fatigue
|
23.2%
26/112 • Number of events 27 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
General disorders
Localised oedema
|
5.4%
6/112 • Number of events 6 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
General disorders
Mucosal inflammation
|
5.4%
6/112 • Number of events 6 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
General disorders
Pyrexia
|
8.9%
10/112 • Number of events 15 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Infections and infestations
Nasopharyngitis
|
6.2%
7/112 • Number of events 10 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Infections and infestations
Urinary tract infection
|
8.9%
10/112 • Number of events 10 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Investigations
Gamma-glutamyltransferase increased
|
6.2%
7/112 • Number of events 7 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Investigations
Weight decreased
|
11.6%
13/112 • Number of events 13 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.1%
18/112 • Number of events 21 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
8.9%
10/112 • Number of events 10 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
6.2%
7/112 • Number of events 9 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
8.9%
10/112 • Number of events 15 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
7.1%
8/112 • Number of events 14 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.9%
10/112 • Number of events 15 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.2%
7/112 • Number of events 7 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.4%
6/112 • Number of events 6 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Nervous system disorders
Dizziness
|
9.8%
11/112 • Number of events 13 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Nervous system disorders
Headache
|
8.9%
10/112 • Number of events 14 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Psychiatric disorders
Insomnia
|
8.9%
10/112 • Number of events 12 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.7%
12/112 • Number of events 13 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.4%
15/112 • Number of events 18 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.2%
7/112 • Number of events 7 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.1%
8/112 • Number of events 8 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.7%
12/112 • Number of events 14 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.2%
7/112 • Number of events 7 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
|
Vascular disorders
Hypotension
|
6.2%
7/112 • Number of events 7 • From the time the informed consent was signed through 90 days after the last dose of the last study treatment or until another therapy was initiated.
AEs were reported spontaneously or in response to open questions, revealed by observation, or were changes from baseline/deterioration in tests and vital signs that met SAE criteria or led to IP discontinuation. AEs/SAEs were followed up for resolution after discontinuation or study completion and for as long as medically indicated.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review publications prior to public release for a period up to 120 days to confirm accuracy, prevent disclosure of confidential information, and ensure that information is handled appropriately.
- Publication restrictions are in place
Restriction type: OTHER