Trial Outcomes & Findings for Durvalumab Long-Term Safety and Efficacy Study (NCT NCT04078152)

Last Updated: 2024-12-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

163 participants

Primary outcome timeframe

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

Results posted on

2024-12-20

Participant Flow

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.

A total of 163 participants were enrolled in this study.

Participant milestones

Participant milestones
Measure	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 milligrams (mg) via intravenous (IV) infusion every 4 weeks on Day 1 of each cycle until confirmed progressive disease (PD), unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	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.	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.
Overall Study STARTED	100	25	38
Overall Study Received Treatment in This Study/Within 90 Days Prior Enrolment in This Study(Safety Analysis Set)	100	7	2
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	100	25	38

Reasons for withdrawal

Reasons for withdrawal
Measure	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 milligrams (mg) via intravenous (IV) infusion every 4 weeks on Day 1 of each cycle until confirmed progressive disease (PD), unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.	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.	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.
Overall Study Other	83	22	25
Overall Study Development of study specific withdrawal criteria	1	1	0
Overall Study Withdrawal by Subject	5	0	1
Overall Study Death	10	2	12
Overall Study Adverse Event	1	0	0

Baseline Characteristics

Durvalumab Long-Term Safety and Efficacy Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Durvalumab Continuation n=100 Participants 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.	Cohort 2: Durvalumab Restart n=25 Participants 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.	Cohort 3: No Restart of Durvalumab n=38 Participants 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.	Total n=163 Participants Total of all reporting groups
Age, Continuous	65.5 years STANDARD_DEVIATION 10.31 • n=5 Participants	66.4 years STANDARD_DEVIATION 9.30 • n=7 Participants	66.1 years STANDARD_DEVIATION 9.95 • n=5 Participants	65.7 years STANDARD_DEVIATION 10.03 • n=4 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants	41 Participants n=4 Participants
Sex: Female, Male Male	82 Participants n=5 Participants	18 Participants n=7 Participants	22 Participants n=5 Participants	122 Participants n=4 Participants
Race/Ethnicity, Customized White	75 Participants n=5 Participants	16 Participants n=7 Participants	21 Participants n=5 Participants	112 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Asian	25 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants	49 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	9 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	91 Participants n=5 Participants	23 Participants n=7 Participants	37 Participants n=5 Participants	151 Participants n=4 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Durvalumab Continuation n=100 Participants 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.	Cohort 2: Durvalumab Restart n=7 Participants 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.	Cohort 3: No Restart of Durvalumab n=2 Participants 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.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AEs	85 Participants	1 Participants	0 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAEs	23 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Durvalumab Continuation n=2 Participants 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.	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.	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.
Cohort 2: Overall Response Rate (ORR)	0 percentage of participants Interval 0.0 to 84.0	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Durvalumab Continuation n=2 Participants 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.	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.	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.
Cohort 2: Duration of Response (DOR)	NA months As no participant in the response evaluable analysis set was assessed to have had either CR or PR, the DOR analysis was not applicable.	—	—

SECONDARY outcome

Timeframe: Up to approximately 37 months

Population: The Full analysis set included all participants enrolled in the study, regardless of the treatment received.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Durvalumab Continuation n=100 Participants 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.	Cohort 2: Durvalumab Restart n=25 Participants 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.	Cohort 3: No Restart of Durvalumab n=38 Participants 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.
Number of Participants Who Were Alive	90 Participants	23 Participants	26 Participants

Adverse Events

Cohort 1: Durvalumab Continuation

Serious events: 23 serious events

Other events: 72 other events

Deaths: 10 deaths

Cohort 2: Durvalumab Restart

Serious events: 0 serious events

Other events: 1 other events

Deaths: 2 deaths

Cohort 3: No Restart of Durvalumab

Serious events: 0 serious events

Other events: 0 other events

Deaths: 12 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER