Trial Outcomes & Findings for Phase II Safety Study of Vemurafenib Followed by Ipilimumab in Subjects With V600 BRAF Mutated Advanced Melanoma (NCT NCT01673854)
NCT ID: NCT01673854
Last Updated: 2018-07-24
Results Overview
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Drug-related=having certain, probable, possible, or unknown relationship to study drug. Grading criteria for AEs: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
70 participants
Primary outcome timeframe
From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred first
Results posted on
2018-07-24
Participant Flow
A total of 70 patients were enrolled, and 46 received treatment.
Participant milestones
| Measure |
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg
Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity.
|
|---|---|
|
Vem 1 Phase (Vemurafenib, 960 mg)
STARTED
|
46
|
|
Vem 1 Phase (Vemurafenib, 960 mg)
COMPLETED
|
46
|
|
Vem 1 Phase (Vemurafenib, 960 mg)
NOT COMPLETED
|
0
|
|
Ipilimumab Phase (Ipilimumab, 10 mg/kg)
STARTED
|
46
|
|
Ipilimumab Phase (Ipilimumab, 10 mg/kg)
COMPLETED
|
19
|
|
Ipilimumab Phase (Ipilimumab, 10 mg/kg)
NOT COMPLETED
|
27
|
|
Vem 2 Phase (Vemurafenib Retreatment)
STARTED
|
19
|
|
Vem 2 Phase (Vemurafenib Retreatment)
COMPLETED
|
0
|
|
Vem 2 Phase (Vemurafenib Retreatment)
NOT COMPLETED
|
19
|
Reasons for withdrawal
| Measure |
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg
Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity.
|
|---|---|
|
Ipilimumab Phase (Ipilimumab, 10 mg/kg)
Disease progression
|
7
|
|
Ipilimumab Phase (Ipilimumab, 10 mg/kg)
Study drug toxicity
|
6
|
|
Ipilimumab Phase (Ipilimumab, 10 mg/kg)
Administrative Reason by Sponsor
|
2
|
|
Ipilimumab Phase (Ipilimumab, 10 mg/kg)
Adverse event unrelated to study drug
|
1
|
|
Ipilimumab Phase (Ipilimumab, 10 mg/kg)
Maximum clinical benefit
|
1
|
|
Ipilimumab Phase (Ipilimumab, 10 mg/kg)
Death
|
1
|
|
Ipilimumab Phase (Ipilimumab, 10 mg/kg)
Not identified
|
2
|
|
Ipilimumab Phase (Ipilimumab, 10 mg/kg)
Not reported
|
7
|
|
Vem 2 Phase (Vemurafenib Retreatment)
Disease progression
|
12
|
|
Vem 2 Phase (Vemurafenib Retreatment)
Study drug toxicity
|
5
|
|
Vem 2 Phase (Vemurafenib Retreatment)
Adverse event unrelated to study drug
|
1
|
|
Vem 2 Phase (Vemurafenib Retreatment)
Death
|
1
|
Baseline Characteristics
Phase II Safety Study of Vemurafenib Followed by Ipilimumab in Subjects With V600 BRAF Mutated Advanced Melanoma
Baseline characteristics by cohort
| Measure |
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg
n=46 Participants
Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity.
|
|---|---|
|
Age, Continuous
|
57.5 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
42 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 Participants
n=5 Participants
|
|
M-Stage at Study Entry
M0
|
6 Participants
n=5 Participants
|
|
M-Stage at Study Entry
M1A
|
8 Participants
n=5 Participants
|
|
M-Stage at Study Entry
M1B
|
8 Participants
n=5 Participants
|
|
M-Stage at Study Entry
M1C
|
24 Participants
n=5 Participants
|
|
Disease Stage at Study Entry
III
|
8 Participants
n=5 Participants
|
|
Disease Stage at Study Entry
IV
|
38 Participants
n=5 Participants
|
|
Number of Disease Sites
1
|
2 Participants
n=5 Participants
|
|
Number of Disease Sites
2
|
8 Participants
n=5 Participants
|
|
Number of Disease Sites
3
|
7 Participants
n=5 Participants
|
|
Number of Disease Sites
4
|
4 Participants
n=5 Participants
|
|
Number of Disease Sites
5 or more
|
25 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0
|
35 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1
|
11 Participants
n=5 Participants
|
|
Time from Diagnosis of Advanced /Metastatic Melanoma to First Vem1 Phase Dose
|
1.86 Months
n=5 Participants
|
PRIMARY outcome
Timeframe: From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred firstPopulation: All participants who received at least 1 dose of ipilimumab
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Drug-related=having certain, probable, possible, or unknown relationship to study drug. Grading criteria for AEs: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.
Outcome measures
| Measure |
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg
n=46 Participants
Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity. Following the end-of-treatment visit, patients entered the Follow-up Phase.
|
|---|---|
|
Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Skin Adverse Events (AEs)
|
32.6 Percentage of participants
Interval 19.5 to 48.0
|
SECONDARY outcome
Timeframe: From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred firstPopulation: All participants who received at least 1 dose of ipilimumab.
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Drug-related=having certain, probable, possible, or unknown relationship to study drug. Grading criteria for AEs: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.
Outcome measures
| Measure |
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg
n=46 Participants
Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity. Following the end-of-treatment visit, patients entered the Follow-up Phase.
|
|---|---|
|
Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Gastrointestinal Adverse Events (AEs)
|
21.7 Percentage of participants
Interval 10.9 to 36.4
|
SECONDARY outcome
Timeframe: From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred firstPopulation: All participants who received at least 1 dose of vemurafenib and ipilimumab
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Drug-related=having certain, probable, possible, or unknown relationship to study drug. Grading criteria for AEs: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.
Outcome measures
| Measure |
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg
n=46 Participants
Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity. Following the end-of-treatment visit, patients entered the Follow-up Phase.
|
|---|---|
|
Percentage of Participants Who Received Ipilimumab and Who Had Grade 3-4 Drug-related Hepatobiliary Adverse Events
|
4.3 Percentage of participants
Interval 0.5 to 14.8
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred firstPopulation: All participants who received at least 1 dose of study drug
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug.
Outcome measures
| Measure |
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg
n=46 Participants
Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity. Following the end-of-treatment visit, patients entered the Follow-up Phase.
|
|---|---|
|
Number of Participants Who Died, Who Died Due to Related Adverse Events (AEs), and With Related AEs, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to AEs and Related AEs, Immune-related (ir) AEs, and Serious irAEs
Deaths due to related AEs
|
0 Participants
|
|
Number of Participants Who Died, Who Died Due to Related Adverse Events (AEs), and With Related AEs, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to AEs and Related AEs, Immune-related (ir) AEs, and Serious irAEs
SAEs
|
31 Participants
|
|
Number of Participants Who Died, Who Died Due to Related Adverse Events (AEs), and With Related AEs, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to AEs and Related AEs, Immune-related (ir) AEs, and Serious irAEs
Discontinuations due to AEs
|
18 Participants
|
|
Number of Participants Who Died, Who Died Due to Related Adverse Events (AEs), and With Related AEs, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to AEs and Related AEs, Immune-related (ir) AEs, and Serious irAEs
Serious irAEs
|
10 Participants
|
|
Number of Participants Who Died, Who Died Due to Related Adverse Events (AEs), and With Related AEs, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to AEs and Related AEs, Immune-related (ir) AEs, and Serious irAEs
Deaths
|
4 Participants
|
|
Number of Participants Who Died, Who Died Due to Related Adverse Events (AEs), and With Related AEs, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to AEs and Related AEs, Immune-related (ir) AEs, and Serious irAEs
Related SAEs
|
18 Participants
|
|
Number of Participants Who Died, Who Died Due to Related Adverse Events (AEs), and With Related AEs, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to AEs and Related AEs, Immune-related (ir) AEs, and Serious irAEs
Discontinuations due to related AEs
|
16 Participants
|
|
Number of Participants Who Died, Who Died Due to Related Adverse Events (AEs), and With Related AEs, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to AEs and Related AEs, Immune-related (ir) AEs, and Serious irAEs
irAEs
|
43 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From the first dose date of Vem1 to the last dose of ipilimumab (to a maximum of 3 years) + 90 days or to the first dose date of Vem2, whichever occurred firstPopulation: All participants who received at least 1 dose of study drug
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.
Outcome measures
| Measure |
Vemurafenib, 960 mg + Ipilimumab, 10 mg/kg
n=46 Participants
Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity. Following the end-of-treatment visit, patients entered the Follow-up Phase.
|
|---|---|
|
Number of Participants With Adverse Events (AEs) Grade 3-4, Related AEs Grade 3-4, Related Serious Adverse Events (SAEs) Grade 3-4, Immune-related (ir) AEs Grade 3-4, and Serious irAEs Grade 3-4
irAEs Grade 3-4
|
25 Participants
|
|
Number of Participants With Adverse Events (AEs) Grade 3-4, Related AEs Grade 3-4, Related Serious Adverse Events (SAEs) Grade 3-4, Immune-related (ir) AEs Grade 3-4, and Serious irAEs Grade 3-4
Related SAEs Grade 3-4
|
17 Participants
|
|
Number of Participants With Adverse Events (AEs) Grade 3-4, Related AEs Grade 3-4, Related Serious Adverse Events (SAEs) Grade 3-4, Immune-related (ir) AEs Grade 3-4, and Serious irAEs Grade 3-4
AEs Grade 3-4
|
39 Participants
|
|
Number of Participants With Adverse Events (AEs) Grade 3-4, Related AEs Grade 3-4, Related Serious Adverse Events (SAEs) Grade 3-4, Immune-related (ir) AEs Grade 3-4, and Serious irAEs Grade 3-4
Related AEs Grade 3-4
|
30 Participants
|
|
Number of Participants With Adverse Events (AEs) Grade 3-4, Related AEs Grade 3-4, Related Serious Adverse Events (SAEs) Grade 3-4, Immune-related (ir) AEs Grade 3-4, and Serious irAEs Grade 3-4
Serious irAEs Grade 3-4
|
9 Participants
|
Adverse Events
Vemurafenib, 960 mg + Ipilimumab,10 mg/kg ab
Serious events: 34 serious events
Other events: 44 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vemurafenib, 960 mg + Ipilimumab,10 mg/kg ab
n=46 participants at risk
Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity.
|
|---|---|
|
Gastrointestinal disorders
Colitis
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Hepatobiliary disorders
Hepatitis
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Renal and urinary disorders
Renal failure
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Abasia
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Metabolism and nutrition disorders
Dehydration
|
4.3%
2/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Vascular disorders
Iliac vein occlusion
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
10.9%
5/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Pancreatitis
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Cardiac disorders
Pericardial effusion
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Abdominal distension
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Blood and lymphatic system disorders
Anaemia
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Nervous system disorders
Headache
|
4.3%
2/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Nervous system disorders
Syncope
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Infections and infestations
Urinary tract infection
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Vomiting
|
4.3%
2/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Asthenia
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Cardiac disorders
Atrial fibrillation
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Nervous system disorders
Cerebral ischaemia
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Vascular disorders
Deep vein thrombosis
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
4.3%
2/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Vascular disorders
Hypotension
|
4.3%
2/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Endocrine disorders
Hypothyroidism
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Pain
|
4.3%
2/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Infections and infestations
Pneumonia
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour associated fever
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
4.3%
2/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Investigations
Blood creatine increased
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Dysphagia
|
4.3%
2/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Investigations
Hepatic enzyme increased
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Injury, poisoning and procedural complications
Wound
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Injury, poisoning and procedural complications
Fall
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Fatigue
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Endocrine disorders
Hypopituitarism
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Pyrexia
|
4.3%
2/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Endocrine disorders
Adrenal Insufficiency
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Endocrine disorders
Hypophysitis
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Infections and infestations
Cellulitis
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Nervous system disorders
Haemorrhage Intracranial
|
4.3%
2/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Autoimmune Colitis
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Peripheral Swelling
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Investigations
Blood Creatinine Increased
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Central Nervous System
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic Malignant Melanoma
|
2.2%
1/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
Other adverse events
| Measure |
Vemurafenib, 960 mg + Ipilimumab,10 mg/kg ab
n=46 participants at risk
Participants received vemurafenib, 960 mg, twice daily for 6 weeks (Vem1 Phase). After a washout period of 3-10 days, patients received ipilimumab, 10 mg/kg, every 3 weeks for a maximum of 4 doses. At Week 24, participants received ipilimumab, 10 mg/kg, every 12 weeks until disease progression or unacceptable toxicity. Patients who did not progress or have unacceptable toxicity in the Vem1 Phase were retreated with vemurafenib (Vem 2 Phase) at the last dose level identified at the end of the Vem1 Phase until disease progression or unacceptable toxicity.
|
|---|---|
|
Investigations
Blood alkaline phosphatase increased
|
23.9%
11/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Colitis
|
10.9%
5/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.4%
8/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
19.6%
9/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Nervous system disorders
Dysgeusia
|
19.6%
9/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Dyspepsia
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Vascular disorders
Flushing
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Nervous system disorders
Hyperaesthesia
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Renal and urinary disorders
Pollakiuria
|
10.9%
5/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Rash
|
67.4%
31/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Eye disorders
Vision blurred
|
17.4%
8/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Metabolism and nutrition disorders
Dehydration
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Blood and lymphatic system disorders
Lymphopenia
|
10.9%
5/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
13.0%
6/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
13.0%
6/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Abdominal distension
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Blood and lymphatic system disorders
Anaemia
|
21.7%
10/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
52.2%
24/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Investigations
Blood sodium decreased
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Constipation
|
19.6%
9/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
41.3%
19/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Nervous system disorders
Headache
|
32.6%
15/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
17.4%
8/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Mucosal inflammation
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
15.2%
7/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Endocrine disorders
Adrenal insufficiency
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Investigations
Blood calcium decreased
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Investigations
Blood creatinine increased
|
17.4%
8/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Nervous system disorders
Dizziness
|
23.9%
11/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Erythema
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Exfoliative rash
|
10.9%
5/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Haemorrhoids
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
15.2%
7/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Investigations
Lipase increased
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
10.9%
5/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Infections and infestations
Urinary tract infection
|
10.9%
5/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Vomiting
|
34.8%
16/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Infections and infestations
Candida infection
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
23/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
10.9%
5/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Endocrine disorders
Hypothyroidism
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
19.6%
9/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Pain
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
26.1%
12/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
15.2%
7/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
41.3%
19/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Investigations
Weight decreased
|
10.9%
5/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Psychiatric disorders
Anxiety
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Vascular disorders
Hot flush
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
13.0%
6/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Endocrine disorders
Hypophysitis
|
15.2%
7/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Oedema peripheral
|
23.9%
11/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Infections and infestations
Sinusitis
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Abdominal pain
|
28.3%
13/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
15.2%
7/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Investigations
Aspartate aminotransferase increased
|
23.9%
11/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
23.9%
11/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Chills
|
21.7%
10/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Dysphagia
|
10.9%
5/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Vascular disorders
Hypertension
|
10.9%
5/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Psychiatric disorders
Insomnia
|
30.4%
14/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Gastrointestinal disorders
Nausea
|
47.8%
22/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Investigations
Alanine aminotransferase increased
|
21.7%
10/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
19.6%
9/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Fatigue
|
52.2%
24/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
8.7%
4/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
15.2%
7/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Investigations
Lymphocyte count decreased
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
General disorders
Pyrexia
|
30.4%
14/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Infections and infestations
Cellulitis
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.5%
3/46 • AEs with onset date on or after Day 1 of study therapy and within the last dose of Vem1 + 14 days, last dose of Ipi Phase + 90 days, last dose of Vem2 + 14 days. Up to July 2014 (approximately 21 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER