Trial Outcomes & Findings for A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors (NCT NCT02403271)
NCT ID: NCT02403271
Last Updated: 2019-01-03
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
124 participants
Primary outcome timeframe
From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Results posted on
2019-01-03
Participant Flow
Participant milestones
| Measure |
Phase 1b
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
|
Phase 2
Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results.
|
|---|---|---|
|
Period 1
STARTED
|
7
|
0
|
|
Period 1
COMPLETED
|
6
|
0
|
|
Period 1
NOT COMPLETED
|
1
|
0
|
|
Period 2
STARTED
|
0
|
124
|
|
Period 2
COMPLETED
|
0
|
0
|
|
Period 2
NOT COMPLETED
|
0
|
124
|
Reasons for withdrawal
| Measure |
Phase 1b
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
|
Phase 2
Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results.
|
|---|---|---|
|
Period 1
Other varied reasons
|
1
|
0
|
|
Period 2
Withdrawal by Subject
|
0
|
14
|
|
Period 2
Death
|
0
|
84
|
|
Period 2
Lost to Follow-up
|
0
|
2
|
|
Period 2
Study Terminated by Sponsor
|
0
|
14
|
|
Period 2
Other varied reasons
|
0
|
10
|
Baseline Characteristics
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors
Baseline characteristics by cohort
| Measure |
Phase 1b/2
n=122 Participants
All participants who received at least one dose of study treatment.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
78 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
44 Participants
n=99 Participants
|
|
Age, Continuous
|
60.0 years
STANDARD_DEVIATION 12.03 • n=99 Participants
|
|
Sex: Female, Male
Female
|
75 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
116 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
104 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
122 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: From the date of first study treatment until DLT or disease progression per RECIST 1.1.Outcome measures
| Measure |
Phase 1b
n=6 Participants
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
|
|---|---|
|
Phase 1b: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) and to Find the Recommended Phase II Dose.
|
6 participants
|
PRIMARY outcome
Timeframe: From the date of first study treatment until progressive disease per RECIST 1.1 or unacceptable toxicity.Population: The Response-evaluable population was participants who received at least 1 dose of treatment (ibrutinib and durvalumab) and provided 1 post-baseline response assessment.
Outcome measures
| Measure |
Phase 1b
n=105 Participants
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
|
|---|---|
|
Phase 2: Efficacy of Ibrutinib in Combination With Durvalumab (MEDI4736) in Participants With Relapsed or Refractory Solid Tumors by Assessing the ORR Per RECIST 1.1.
|
2 Participants
|
SECONDARY outcome
Timeframe: 0hr, 1hr, 2hr, and 4hr post-dosePopulation: All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data. Data were analyzed together for Phase 1b and Phase 2 because the dose was the same.
Cmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1.
Outcome measures
| Measure |
Phase 1b
n=34 Participants
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
|
|---|---|
|
Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib
|
218 ng/mL
Standard Deviation 163
|
SECONDARY outcome
Timeframe: 0hr, 1hr, 2hr, and 4hr post-dosePopulation: All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data. Data were analyzed together for Phase 1b/2 because the dose was the same.
AUC0-24 = the area under the plasma concentration-time curve of ibrutinib during the dosing interval on Cycle 3 Day 1
Outcome measures
| Measure |
Phase 1b
n=34 Participants
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
|
|---|---|
|
Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib
|
2126 h.ng/mL
Standard Deviation 1315
|
SECONDARY outcome
Timeframe: 60 minutes post-dose (dose administered as an infusion over a 1 hour period)Population: All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data.
Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1.
Outcome measures
| Measure |
Phase 1b
n=8 Participants
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
|
|---|---|
|
Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)
|
386 μg/mL
Geometric Coefficient of Variation 19.5
|
SECONDARY outcome
Timeframe: Pre-dosePopulation: All participants who received at least one dose of study treatment and had evaluable pharmacokinetic data.
Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1
Outcome measures
| Measure |
Phase 1b
n=10 Participants
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
|
|---|---|
|
Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)
|
168 μg/mL
Geometric Coefficient of Variation 19.6
|
SECONDARY outcome
Timeframe: From the date of first study treatment until DLT or disease progression per RECIST 1.1.Population: Data not collected
BTK occupancy
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From the date of first study treatment until DLT or disease progression per RECIST 1.1.Population: Participants who enrolled and received at least 1 dose of study treatment.
Outcome measures
| Measure |
Phase 1b
n=122 Participants
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
|
|---|---|
|
Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)
|
122 Participants
|
SECONDARY outcome
Timeframe: Pre-dosePopulation: All subjects who received at least one dose of ibrutinib and who had at least one evaluable BTK occupancy assay result at Cycle 3 Day 1.
BTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1.
Outcome measures
| Measure |
Phase 1b
n=30 Participants
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6 + 3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
|
|---|---|
|
Phase 2: Pharmacodynamics
|
87.8 percentage of BTK binding site occupancy
Standard Error 4.2
|
Adverse Events
Phase 1b/2
Serious events: 77 serious events
Other events: 122 other events
Deaths: 96 deaths
Serious adverse events
| Measure |
Phase 1b/2
n=122 participants at risk
All subjects who received at least one dose of study treatment.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Cardiac disorders
Pericardial effusion
|
2.5%
3/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Cardiac disorders
Supraventricular tachycardia
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Cardiac disorders
Atrial fibrillation
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Cardiac disorders
Sinus tachycardia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Cardiac disorders
Ventricular tachycardia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Endocrine disorders
Hypothyroidism
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Abdominal pain
|
3.3%
4/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Diarrhoea
|
2.5%
3/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Vomiting
|
2.5%
3/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Constipation
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Nausea
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Ascites
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Obstruction gastric
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
General disorders
Pyrexia
|
4.9%
6/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
General disorders
Death
|
2.5%
3/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
General disorders
Multiple organ dysfunction syndrome
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
General disorders
Asthenia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
General disorders
Malaise
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
General disorders
Oedema peripheral
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Hepatobiliary disorders
Cholangitis
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Hepatobiliary disorders
Hepatic failure
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Hepatobiliary disorders
Pneumonia
|
6.6%
8/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Sepsis
|
3.3%
4/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Cellulitis
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Pneumonia bacterial
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Urinary tract infection
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Diverticulitis
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Escherichia sepsis
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Gastroenteritis
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Pyelonephritis
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Serratia bacteraemia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Staphylococcal sepsis
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Injury, poisoning and procedural complications
Compression fracture
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Dehydration
|
4.9%
6/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
3.3%
4/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
|
11.5%
14/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
4.9%
6/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Nervous system disorders
Cerebrovascular accident
|
2.5%
3/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Nervous system disorders
Embolic stroke
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Nervous system disorders
Metabolic encephalopathy
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Nervous system disorders
Seizure
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Psychiatric disorders
Mental status changes
|
3.3%
4/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Renal and urinary disorders
Acute kidney injury
|
2.5%
3/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Renal and urinary disorders
Urinary retention
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Renal and urinary disorders
Haematuria
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Renal and urinary disorders
Obstructive uropathy
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Renal and urinary disorders
Renal failure
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Reproductive system and breast disorders
Breast mass
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.1%
5/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
4.1%
5/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
2.5%
3/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.5%
3/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Alveolitis allergic
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Vascular disorders
Hypotension
|
2.5%
3/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Vascular disorders
Deep vein thrombosis
|
1.6%
2/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Pneumonia
|
6.6%
8/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Stenotrophomonas sepsis
|
0.82%
1/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.5%
3/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
Other adverse events
| Measure |
Phase 1b/2
n=122 participants at risk
All subjects who received at least one dose of study treatment.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
21.3%
26/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Nausea
|
27.0%
33/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Diarrhoea
|
18.0%
22/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Abdominal pain
|
15.6%
19/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Constipation
|
17.2%
21/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Vomiting
|
15.6%
19/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Stomatitis
|
13.1%
16/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Dyspepsia
|
6.6%
8/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.7%
7/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
General disorders
Fatigue
|
43.4%
53/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
General disorders
Oedema peripheral
|
21.3%
26/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
General disorders
Pyrexia
|
15.6%
19/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Infections and infestations
Urinary tract infection
|
6.6%
8/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Investigations
Aspartate aminotransferase increase
|
12.3%
15/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Investigations
Weight decreased
|
9.8%
12/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Investigations
Alanine aminotransferase increased
|
9.0%
11/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Investigations
Blood alkaline phosphatase increased
|
6.6%
8/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
26.2%
32/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
23.0%
28/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
12.3%
15/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
10.7%
13/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Dehydration
|
7.4%
9/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
6.6%
8/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.8%
12/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.8%
12/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.8%
12/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
9.0%
11/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
6.6%
8/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.6%
8/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Nervous system disorders
Dizziness
|
10.7%
13/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Nervous system disorders
Headache
|
9.8%
12/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Psychiatric disorders
Insomnia
|
6.6%
8/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
17.2%
21/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.9%
17/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.8%
12/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
15.6%
19/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
11.5%
14/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
9.0%
11/122 • 2 years, 5 months
Adverse events were not collected by phase (Arm) because the treatments between Phase 1b and Phase 2 were not appreciably different.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 1. Institution/Investigator will not publish without Sponsor prior review and approval 2. Institution/Investigator will not publish until the earlier of (i) results of study are submitted for publication (ii) notification that submission of the multicenter results are no longer planned (iii) 18 months after study termination
- Publication restrictions are in place
Restriction type: OTHER