Solid Tumor
Conditions
Keywords
non-small cell lung cancer (NSCLC), urothelial cancer, durvalumab, long-term safety, efficacy, overall survival, immunotherapy, checkpoint inhibitor, PD-L1, retreatment, Gastric adenocarcinoma
Brief summary
The aims of the study are to monitor the long-term safety of durvalumab, to provide continued treatment or retreatment with durvalumab to eligible patients, and to collect overall survival (OS) information.
Detailed description
This is a multicenter, open-label, global study that will enroll patients who are currently receiving durvalumab monotherapy, or have previously received durvalumab as monotherapy or in combination with any other approved or investigational anticancer agents, in an eligible AstraZeneca/MedImmune-sponsored clinical study.
Interventions
DRUGDurvalumab
IV infusion q4w with 1500mg durvalumab until progressive disease
Sponsors
Iqvia Pty Ltd
Parexel
Medidata Solutions
CISCRP
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
All involved know the identity of the intervention assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
1. Patient must be 18 years or older, at the time of signing the ICF. For subjects aged \< 20 years and enrolled in Japan, a written ICF should be obtained from the subject and his or her legally acceptable representative. 2. Patient received durvalumab monotherapy and/or durvalumab containing combination in an AstraZeneca/MedImmune-sponsored parent clinical study that is approved for enrollment into this study. 3. Patients who received durvalumab in combination with any other approved or investigational anticancer agents in the parent clinical study must have completed or discontinued all other anticancer therapy (beyond durvalumab regimen). 4. Patient must be willing and able to provide written informed consent and to comply with scheduled visits and other study procedures.
Exclusion criteria
The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From the time of signing the informed consent form until the follow-up period is completed (90 days after the last dose of durvalumab); approximately 37 months | An AE was the development of any untoward medical occurrence (other than progression of the malignancy under evaluation) in a participant or clinical study participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. A SAE was an AE occurring during any study phase that fulfilled one or more of the following: resulted in death; was immediately life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; was a congenital abnormality or birth defect; was an important medical event that jeopardized the participant or required medical treatment to prevent one of the outcomes listed above. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 2: Overall Response Rate (ORR) | Tumor assessments as determined by the Investigator (at least every 12 weeks) until withdrawal of consent, progression or death; approximately 30 months | The ORR was defined as the percentage of participants with a confirmed investigator-assessed response of either complete response (CR) or partial response (PR) from the date of re-initiation of treatment with durvalumab monotherapy. Tumor assessments were performed according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). CR was defined as the disappearance of all target lesions (TLs) since baseline and reduction in short axis diameter to \<10 millimeters (mm) for any pathological lymph nodes selected as TLs. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameter. |
| Cohort 2: Duration of Response (DOR) | Tumor assessments as determined by the Investigator (at least every 12 weeks) until withdrawal of consent, progression or death; approximately 30 months | The DOR was defined as the time from first documented CR or PR to time of first documented disease progression or death in the absence of disease progression. Tumor assessments were performed according to RECIST v1.1. |
| Number of Participants Who Were Alive | Up to approximately 37 months | Number of participants who were alive are reported in this outcome measure. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, Czechia, France, Germany, Greece, Hungary, India, Israel, Japan, Malaysia, Netherlands, Poland, Romania, Russia, Serbia, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States, Vietnam
Participant flow
Recruitment details
This Phase IV, open-label study was conducted at 112 investigational sites across 31 countries in participants who were receiving durvalumab monotherapy and/or those who previously received durvalumab as a monotherapy or in combination with any other approved or investigational anticancer agent in previously enrolled parent study between 05 Sep 2019 and 31 Oct 2022.
Pre-assignment details
A total of 163 participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Durvalumab Continuation Cohort 1 included participants who had received durvalumab monotherapy or durvalumab combination therapy under the parent clinical study (including those who underwent retreatment per the parent study) who had not clinically progressed and who were eligible to continue durvalumab treatment after completing dosing of all other anticancer agents, including other investigational agents. Participants received durvalumab monotherapy 1500 mg via IV infusion every 4 weeks on Day 1 of each cycle until confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. | 100 |
| Cohort 2: Durvalumab Restart Cohort 2 included participants who had completed durvalumab monotherapy or combination therapy with any other approved or investigational anticancer agents in a parent study, without confirmed PD during the period of treatment, and who were potentially eligible for retreatment with durvalumab. Participants received durvalumab monotherapy 1500 mg via IV infusion every 4 weeks on Day 1 of each cycle until confirmed PD, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met. | 25 |
| Cohort 3: No Restart of Durvalumab Cohort 3 included participants previously treated with durvalumab monotherapy or in combination with any other approved or investigational anticancer agents who were no longer receiving durvalumab and were not eligible to receive retreatment. Participants did not receive any study drug. | 38 |
| Total | 163 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Death | 10 | 2 | 12 |
| Overall Study | Development of study specific withdrawal criteria | 1 | 1 | 0 |
| Overall Study | Other | 83 | 22 | 25 |
| Overall Study | Withdrawal by Subject | 5 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: Durvalumab Continuation | Cohort 2: Durvalumab Restart | Cohort 3: No Restart of Durvalumab | Total |
|---|---|---|---|---|
| Age, Continuous | 65.5 years STANDARD_DEVIATION 10.31 | 66.4 years STANDARD_DEVIATION 9.3 | 66.1 years STANDARD_DEVIATION 9.95 | 65.7 years STANDARD_DEVIATION 10.03 |
| Race/Ethnicity, Customized Asian | 25 Participants | 8 Participants | 16 Participants | 49 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 9 Participants | 0 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 91 Participants | 23 Participants | 37 Participants | 151 Participants |
| Race/Ethnicity, Customized White | 75 Participants | 16 Participants | 21 Participants | 112 Participants |
| Sex: Female, Male Female | 18 Participants | 7 Participants | 16 Participants | 41 Participants |
| Sex: Female, Male Male | 82 Participants | 18 Participants | 22 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 10 / 100 | 2 / 25 | 12 / 38 |
| other Total, other adverse events | 72 / 100 | 1 / 7 | 0 / 2 |
| serious Total, serious adverse events | 23 / 100 | 0 / 7 | 0 / 2 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was the development of any untoward medical occurrence (other than progression of the malignancy under evaluation) in a participant or clinical study participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. A SAE was an AE occurring during any study phase that fulfilled one or more of the following: resulted in death; was immediately life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; was a congenital abnormality or birth defect; was an important medical event that jeopardized the participant or required medical treatment to prevent one of the outcomes listed above.
Time frame: From the time of signing the informed consent form until the follow-up period is completed (90 days after the last dose of durvalumab); approximately 37 months
Population: The Safety analysis set included those participants who received at least 1 dose of durvalumab in this study or enrolled in this study within 90 days of the last dose of durvalumab or durvalumab combination in the respective parent clinical study. The data is from this study only, parent study data is not included in this table.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Durvalumab Continuation | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 85 Participants |
| Cohort 1: Durvalumab Continuation | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 23 Participants |
| Cohort 2: Durvalumab Restart | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 1 Participants |
| Cohort 2: Durvalumab Restart | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| Cohort 3: No Restart of Durvalumab | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 0 Participants |
| Cohort 3: No Restart of Durvalumab | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
Secondary
Cohort 2: Duration of Response (DOR)
The DOR was defined as the time from first documented CR or PR to time of first documented disease progression or death in the absence of disease progression. Tumor assessments were performed according to RECIST v1.1.
Time frame: Tumor assessments as determined by the Investigator (at least every 12 weeks) until withdrawal of consent, progression or death; approximately 30 months
Population: The Response evaluable analysis set included those participants who underwent retreatment with durvalumab in Cohort 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Durvalumab Continuation | Cohort 2: Duration of Response (DOR) | NA months |
Secondary
Cohort 2: Overall Response Rate (ORR)
The ORR was defined as the percentage of participants with a confirmed investigator-assessed response of either complete response (CR) or partial response (PR) from the date of re-initiation of treatment with durvalumab monotherapy. Tumor assessments were performed according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). CR was defined as the disappearance of all target lesions (TLs) since baseline and reduction in short axis diameter to \<10 millimeters (mm) for any pathological lymph nodes selected as TLs. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameter.
Time frame: Tumor assessments as determined by the Investigator (at least every 12 weeks) until withdrawal of consent, progression or death; approximately 30 months
Population: The Response evaluable analysis set included those participants who underwent retreatment with durvalumab in Cohort 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Durvalumab Continuation | Cohort 2: Overall Response Rate (ORR) | 0 percentage of participants |
Secondary
Number of Participants Who Were Alive
Number of participants who were alive are reported in this outcome measure. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.
Time frame: Up to approximately 37 months
Population: The Full analysis set included all participants enrolled in the study, regardless of the treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Durvalumab Continuation | Number of Participants Who Were Alive | 90 Participants |
| Cohort 2: Durvalumab Restart | Number of Participants Who Were Alive | 23 Participants |
| Cohort 3: No Restart of Durvalumab | Number of Participants Who Were Alive | 26 Participants |