Trial Outcomes & Findings for Phase II MEDI4736 in Combination With Chemotherapy for First-Line Treatment of Unresectable Mesothelioma (NCT NCT02899195)
NCT ID: NCT02899195
Last Updated: 2023-07-05
Results Overview
Overall survival (OS) is defined as the time from randomization to death from any cause. Patients that have not had an event reported at analysis will be censored at their date of last follow-up.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
55 participants
Primary outcome timeframe
From randomization until death, up to 32 months
Results posted on
2023-07-05
Participant Flow
Participant milestones
| Measure |
Concurrent Durvalumab Then Maintenance Durvalumab
Pemetrexed/cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab every 3 weeks. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity at the investigator's discretion.
Concurrent Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV will be administered before pemetrexed and cisplatin chemotherapy over approximately 60 minutes. Approximately 30 minutes after the durvalumab infusion is complete, pemetrexed 500 mg/m² IV will be administered over 10 minutes. Cisplatin 75 mg/m² IV over 2 hours will begin approximately 30 minutes after the end of pemetrexed administration. If carboplatin is substituted for cisplatin, carboplatin Area Under the Concentration-Time Curve (AUC) 5 will be infused over 30 minutes beginning approximately 15-30 minutes after the end of the pemetrexed administration.
After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment.
Maintenance Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV over approximately 60 minutes.
|
|---|---|
|
Maintenance Durvalumab
STARTED
|
44
|
|
Maintenance Durvalumab
COMPLETED
|
10
|
|
Maintenance Durvalumab
NOT COMPLETED
|
34
|
|
Concurrent Durvalumab
STARTED
|
55
|
|
Concurrent Durvalumab
COMPLETED
|
44
|
|
Concurrent Durvalumab
NOT COMPLETED
|
11
|
Reasons for withdrawal
| Measure |
Concurrent Durvalumab Then Maintenance Durvalumab
Pemetrexed/cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab every 3 weeks. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity at the investigator's discretion.
Concurrent Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV will be administered before pemetrexed and cisplatin chemotherapy over approximately 60 minutes. Approximately 30 minutes after the durvalumab infusion is complete, pemetrexed 500 mg/m² IV will be administered over 10 minutes. Cisplatin 75 mg/m² IV over 2 hours will begin approximately 30 minutes after the end of pemetrexed administration. If carboplatin is substituted for cisplatin, carboplatin Area Under the Concentration-Time Curve (AUC) 5 will be infused over 30 minutes beginning approximately 15-30 minutes after the end of the pemetrexed administration.
After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment.
Maintenance Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV over approximately 60 minutes.
|
|---|---|
|
Concurrent Durvalumab
Adverse Event
|
4
|
|
Concurrent Durvalumab
Physician Decision
|
1
|
|
Concurrent Durvalumab
Withdrawal by Subject
|
1
|
|
Concurrent Durvalumab
Progressive Disease
|
5
|
|
Maintenance Durvalumab
Adverse Event
|
1
|
|
Maintenance Durvalumab
Physician Decision
|
1
|
|
Maintenance Durvalumab
Withdrawal by Subject
|
1
|
|
Maintenance Durvalumab
Progressive Disease
|
31
|
Baseline Characteristics
Phase II MEDI4736 in Combination With Chemotherapy for First-Line Treatment of Unresectable Mesothelioma
Baseline characteristics by cohort
| Measure |
Concurrent Durvalumab Then Maintenance Durvalumab
n=55 Participants
Pemetrexed/cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab every 3 weeks. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity at the investigator's discretion.
Concurrent Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV will be administered before pemetrexed and cisplatin chemotherapy over approximately 60 minutes. Approximately 30 minutes after the durvalumab infusion is complete, pemetrexed 500 mg/m² IV will be administered over 10 minutes. Cisplatin 75 mg/m² IV over 2 hours will begin approximately 30 minutes after the end of pemetrexed administration. If carboplatin is substituted for cisplatin, carboplatin Area Under the Concentration-Time Curve (AUC) 5 will be infused over 30 minutes beginning approximately 15-30 minutes after the end of the pemetrexed administration.
After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment.
Maintenance Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV over approximately 60 minutes.
|
|---|---|
|
Age, Continuous
|
68.4 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
47 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
|
Histologic subtype
Epithelioid
|
41 Participants
n=5 Participants
|
|
Histologic subtype
Sarcomatoid
|
7 Participants
n=5 Participants
|
|
Histologic subtype
Biphasic
|
6 Participants
n=5 Participants
|
|
Histologic subtype
Desmoplastic
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From randomization until death, up to 32 monthsPopulation: All eligible and treated patients
Overall survival (OS) is defined as the time from randomization to death from any cause. Patients that have not had an event reported at analysis will be censored at their date of last follow-up.
Outcome measures
| Measure |
Concurrent Durvalumab Then Maintenance Durvalumab
n=55 Participants
Pemetrexed/cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab every 3 weeks. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity at the investigator's discretion.
Concurrent Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV will be administered before pemetrexed and cisplatin chemotherapy over approximately 60 minutes. Approximately 30 minutes after the durvalumab infusion is complete, pemetrexed 500 mg/m² IV will be administered over 10 minutes. Cisplatin 75 mg/m² IV over 2 hours will begin approximately 30 minutes after the end of pemetrexed administration. If carboplatin is substituted for cisplatin, carboplatin Area Under the Concentration-Time Curve (AUC) 5 will be infused over 30 minutes beginning approximately 15-30 minutes after the end of the pemetrexed administration.
After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment.
Maintenance Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV over approximately 60 minutes.
|
|---|---|
|
Overall Survival (OS)
|
20.4 months
Interval 13.0 to 28.5
|
SECONDARY outcome
Timeframe: Up to 15 months from start of treatmentPopulation: treated population
Number of participants with abnormal laboratory values and/or adverse events related to treatment.
Outcome measures
| Measure |
Concurrent Durvalumab Then Maintenance Durvalumab
n=55 Participants
Pemetrexed/cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab every 3 weeks. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity at the investigator's discretion.
Concurrent Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV will be administered before pemetrexed and cisplatin chemotherapy over approximately 60 minutes. Approximately 30 minutes after the durvalumab infusion is complete, pemetrexed 500 mg/m² IV will be administered over 10 minutes. Cisplatin 75 mg/m² IV over 2 hours will begin approximately 30 minutes after the end of pemetrexed administration. If carboplatin is substituted for cisplatin, carboplatin Area Under the Concentration-Time Curve (AUC) 5 will be infused over 30 minutes beginning approximately 15-30 minutes after the end of the pemetrexed administration.
After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment.
Maintenance Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV over approximately 60 minutes.
|
|---|---|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03
|
36 Participants
|
SECONDARY outcome
Timeframe: From randomization until disease progression or death from any cause, up to 32 monthsPopulation: Eligible and treated population
Progression-free survival (PFS) is defined as the time from randomization to documented disease progression or death from any cause, whichever occurs first. Patients who have not experienced an event of interest by the time of analysis will be censored at the date they are last known to be alive and progression-free.
Outcome measures
| Measure |
Concurrent Durvalumab Then Maintenance Durvalumab
n=55 Participants
Pemetrexed/cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab every 3 weeks. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity at the investigator's discretion.
Concurrent Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV will be administered before pemetrexed and cisplatin chemotherapy over approximately 60 minutes. Approximately 30 minutes after the durvalumab infusion is complete, pemetrexed 500 mg/m² IV will be administered over 10 minutes. Cisplatin 75 mg/m² IV over 2 hours will begin approximately 30 minutes after the end of pemetrexed administration. If carboplatin is substituted for cisplatin, carboplatin Area Under the Concentration-Time Curve (AUC) 5 will be infused over 30 minutes beginning approximately 15-30 minutes after the end of the pemetrexed administration.
After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment.
Maintenance Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV over approximately 60 minutes.
|
|---|---|
|
Progression-Free Survival (PFS)
|
6.7 month
Interval 6.1 to 8.4
|
SECONDARY outcome
Timeframe: From time concurrent treatment started until progression, up to 32 monthsPopulation: Eligible and treated patients
TTP measured from the time concurrent treatment with chemotherapy/durvalumab begins until radiologic or clinical progression is noted.
Outcome measures
| Measure |
Concurrent Durvalumab Then Maintenance Durvalumab
n=55 Participants
Pemetrexed/cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab every 3 weeks. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity at the investigator's discretion.
Concurrent Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV will be administered before pemetrexed and cisplatin chemotherapy over approximately 60 minutes. Approximately 30 minutes after the durvalumab infusion is complete, pemetrexed 500 mg/m² IV will be administered over 10 minutes. Cisplatin 75 mg/m² IV over 2 hours will begin approximately 30 minutes after the end of pemetrexed administration. If carboplatin is substituted for cisplatin, carboplatin Area Under the Concentration-Time Curve (AUC) 5 will be infused over 30 minutes beginning approximately 15-30 minutes after the end of the pemetrexed administration.
After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment.
Maintenance Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV over approximately 60 minutes.
|
|---|---|
|
Time to Progression (TTP) on Durvalumab
|
6.8 months
Interval 6.2 to 8.4
|
SECONDARY outcome
Timeframe: From randomization until end of treatment, up to 15 monthsPopulation: Eligible and treated patient population
ORR assessed in accordance with RECIST 1.1 (modified for malignant mesothelioma).
Outcome measures
| Measure |
Concurrent Durvalumab Then Maintenance Durvalumab
n=55 Participants
Pemetrexed/cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab every 3 weeks. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity at the investigator's discretion.
Concurrent Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV will be administered before pemetrexed and cisplatin chemotherapy over approximately 60 minutes. Approximately 30 minutes after the durvalumab infusion is complete, pemetrexed 500 mg/m² IV will be administered over 10 minutes. Cisplatin 75 mg/m² IV over 2 hours will begin approximately 30 minutes after the end of pemetrexed administration. If carboplatin is substituted for cisplatin, carboplatin Area Under the Concentration-Time Curve (AUC) 5 will be infused over 30 minutes beginning approximately 15-30 minutes after the end of the pemetrexed administration.
After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment.
Maintenance Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV over approximately 60 minutes.
|
|---|---|
|
Objective Response Rate (ORR)
|
31 Participants
|
Adverse Events
Concurrent Durvalumab Then Maintenance Durvalumab
Serious events: 36 serious events
Other events: 55 other events
Deaths: 33 deaths
Serious adverse events
| Measure |
Concurrent Durvalumab Then Maintenance Durvalumab
n=55 participants at risk
Pemetrexed/cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab every 3 weeks. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity at the investigator's discretion.
Concurrent Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV will be administered before pemetrexed and cisplatin chemotherapy over approximately 60 minutes. Approximately 30 minutes after the durvalumab infusion is complete, pemetrexed 500 mg/m² IV will be administered over 10 minutes. Cisplatin 75 mg/m² IV over 2 hours will begin approximately 30 minutes after the end of pemetrexed administration. If carboplatin is substituted for cisplatin, carboplatin Area Under the Concentration-Time Curve (AUC) 5 will be infused over 30 minutes beginning approximately 15-30 minutes after the end of the pemetrexed administration.
After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment.
Maintenance Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV over approximately 60 minutes.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
20.0%
11/55 • Number of events 11 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Blood and lymphatic system disorders
Lymphopenia
|
3.6%
2/55 • Number of events 2 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.5%
3/55 • Number of events 3 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Cardiac disorders
Atrial fibrillation
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Cardiac disorders
Pericardial effusion
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Ear and labyrinth disorders
Deafness
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Gastrointestinal disorders
Stomatitis
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
General disorders
Fatigue
|
7.3%
4/55 • Number of events 4 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Infections and infestations
Cellulitis
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Infections and infestations
Peritonitis
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Infections and infestations
Pneumonia
|
3.6%
2/55 • Number of events 2 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Infections and infestations
Sepsis
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Alanine aminotransferase increased
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Amylase increased
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Aspartate aminotransferase increased
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Blood alkaline phosphatase increased
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Blood creatinine increased
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Platelet count decreased
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
White blood cell count decreased
|
5.5%
3/55 • Number of events 3 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Dehydration
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
9.1%
5/55 • Number of events 5 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Nervous system disorders
Encephalopathy
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Nervous system disorders
Lethargy
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Nervous system disorders
Syncope
|
3.6%
2/55 • Number of events 2 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Nervous system disorders
Confusional state
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Renal and urinary disorders
Acute kidney injury
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
3.6%
2/55 • Number of events 2 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Vascular disorders
Embolism
|
3.6%
2/55 • Number of events 2 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Vascular disorders
Hypertension
|
5.5%
3/55 • Number of events 3 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Vascular disorders
Hypertensive emergency
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Vascular disorders
Peripheral artery thrombosis
|
1.8%
1/55 • Number of events 1 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
Other adverse events
| Measure |
Concurrent Durvalumab Then Maintenance Durvalumab
n=55 participants at risk
Pemetrexed/cisplatin will be given for up to six 3-week cycles with the addition of concurrent durvalumab every 3 weeks. Use of carboplatin in place of cisplatin will be permitted for patients who are ineligible for cisplatin due to impaired renal function at screening. For patients that receive cisplatin, carboplatin may also be substituted after Cycle 1 for cisplatin related toxicity at the investigator's discretion.
Concurrent Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV will be administered before pemetrexed and cisplatin chemotherapy over approximately 60 minutes. Approximately 30 minutes after the durvalumab infusion is complete, pemetrexed 500 mg/m² IV will be administered over 10 minutes. Cisplatin 75 mg/m² IV over 2 hours will begin approximately 30 minutes after the end of pemetrexed administration. If carboplatin is substituted for cisplatin, carboplatin Area Under the Concentration-Time Curve (AUC) 5 will be infused over 30 minutes beginning approximately 15-30 minutes after the end of the pemetrexed administration.
After completion of Cycle 6 of concurrent therapy, patients with stable or responding disease per modified RECIST for malignant mesothelioma will continue on single agent durvalumab every 3 weeks until progression. Maximum duration of durvalumab treatment is 12 months starting from Cycle 1 of concurrent treatment.
Maintenance Durvalumab: On Day 1 of each 21 day cycle: Durvalumab 1120 mg IV over approximately 60 minutes.
|
|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
7.3%
4/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
10.9%
6/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
14.5%
8/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.1%
5/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
18.2%
10/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
14.5%
8/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.5%
8/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
14.5%
8/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.3%
4/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Nervous system disorders
Dizziness
|
14.5%
8/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Nervous system disorders
Headache
|
10.9%
6/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Nervous system disorders
Memory impairment
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Nervous system disorders
Neuropathy peripheral
|
9.1%
5/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Nervous system disorders
Paraesthesia
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
7.3%
4/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Psychiatric disorders
Anxiety
|
7.3%
4/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Psychiatric disorders
Confusional state
|
5.5%
3/55 • Number of events 3 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Psychiatric disorders
Depression
|
9.1%
5/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Psychiatric disorders
Insomnia
|
14.5%
8/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Renal and urinary disorders
Acute kidney injury
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Renal and urinary disorders
Dysuria
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Renal and urinary disorders
Proteinuria
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
32.7%
18/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
34.5%
19/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
9.1%
5/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Reproductive system and breast disorders
Oropharyngeal pain
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
9.1%
5/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
18.2%
10/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Reproductive system and breast disorders
Upper-airway cough syndrome
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.3%
4/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
18.2%
10/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
20.0%
11/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Vascular disorders
Hot flush
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Vascular disorders
Hypotension
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Blood and lymphatic system disorders
Anaemia
|
36.4%
20/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Endocrine disorders
Hyperthyroidism
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Endocrine disorders
Hypothyroidism
|
14.5%
8/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Eye disorders
Dry eye
|
12.7%
7/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Eye disorders
Lacrimation increased
|
7.3%
4/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Gastrointestinal disorders
Abdominal distension
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Gastrointestinal disorders
Abdominal pain
|
7.3%
4/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Gastrointestinal disorders
Constipation
|
49.1%
27/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Gastrointestinal disorders
Diarrhoea
|
23.6%
13/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
9.1%
5/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Gastrointestinal disorders
Nausea
|
56.4%
31/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Gastrointestinal disorders
Vomiting
|
23.6%
13/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
General disorders
Asthenia
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
General disorders
Fatigue
|
60.0%
33/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
General disorders
Mucosal inflammation
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
General disorders
Oedema peripheral
|
16.4%
9/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
General disorders
Pyrexia
|
12.7%
7/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Infections and infestations
Upper respiratory tract infection
|
7.3%
4/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Infections and infestations
Urinary tract infection
|
7.3%
4/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Injury, poisoning and procedural complications
Contusion
|
7.3%
4/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Injury, poisoning and procedural complications
Fall
|
10.9%
6/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Alanine aminotransferase increased
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Aspartate aminotransferase increased
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Blood alkaline phosphatase increased
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Blood creatinine increased
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Lymphocyte count decreased
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Neutrophil count decreased
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Platelet count decreased
|
5.5%
3/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Investigations
Weight decreased
|
16.4%
9/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
27.3%
15/55 • Adverse Events monitored for up to 15 months from start of treatment; deaths monitored from randomization for up to 32 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60