Study of Durvalumab following radiation therapy in patients with stage 3 unresectable NSCLC ineligible for chemotherapy - DUART

Study identifier:D4194C00009

ClinicalTrials.gov identifier:NCT04249362

EudraCT identifier:2019-004336-31

CTIS identifier:N/A

Study Complete

Official Title

A Phase II, Open-label, Multicenter, International Study of Durvalumab Following Radiation Therapy in Patients with Stage III, Unresectable Non-Small Cell Lung Cancer Who Are Ineligible for Chemotherapy

Medical condition

Non-small Cell Lung Cancer

Phase

Phase 2

Healthy volunteers

Study drug

Durvalumab

Sex

All

Actual Enrollment

102

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 26 Nov 2020

Primary Completion Date: 30 Mar 2023

Study Completion Date: 25 Nov 2024

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Capable of giving signed informed consent.
2. Age ≥ 18 years at study entry.
3. Histologically or cytologically documented NSCLC with locally-advanced, unresectable Stage III disease.
4. Deemed ineligible for chemotherapy per Investigator assessment.
5. Receipt of radiation therapy that was completed within 42 days prior to first study drug administration.
6. Must have received a total dose of radiation of 40 to 66 Gy (standard or hypofractionated BED).
7. Must not have progressed following radiation therapy, as per Investigator assessed RECIST 1.1 criteria: a) Patients with measurable disease and/or nonmeasurable and/or no evidence of disease assessed at baseline by computed tomography /magnetic resonance imaging will be eligible for this study. b) Prior irradiated lesions may be considered measurable and selected as target lesions (TLs) providing they fulfill the other criteria for measurability.
8. World Health Organization/ECOG performance status of ≤2.
9. No prior exposure to immune-mediated therapy including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1, and antiprogrammed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
10. Patients must have adequate organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count ≥ 1.0 × 109 /L
• Platelet count ≥ 75 × 109/L
• Serum bilirubin ≤ 1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome.
• Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × ULN
• Measured creatinine clearance > 30 mL/min or calculated CL > 30 mL/min as determined by Cockcroft-Gault
11. Life expectancy of greater than 12 weeks.
12. Body weight greater than 30 kg at study entry and at first study drug administration

Exclusion Criteria

1. Patients with locally-advanced NSCLC whose disease has progressed following radiation therapy.
2. Mixed small cell lung cancer and NSCLC histology.
3. History of allogeneic organ transplantation.
4. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome).
5. Uncontrolled intercurrent illness (e.g., ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris)
6. History of another primary malignancy except for (a) malignancy treated with curative intent and with no known active disease ≥ 5 years before the first study drug administration, (b) adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease, and c) treated carcinoma in situ without evidence of disease.
7. History of leptomeningeal carcinomatosis
8. History of active primary immunodeficiency
9. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
10. Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia, and the laboratory values defined in the inclusion criteria
11. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
12. Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab
13. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of durvalumab.
14. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
15. Participation in another clinical study with an IP administered in the last 4 weeks.
16. Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
17. Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment
18. Patients who refuse chemotherapy by their own decision.
19. Involvement in the planning and/or conduct of the study
20. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control.
21. Judgment by the Investigator that the patient should not participate in the study
22. Genetics research study (optional):
Exclusion criteria for participation in the optional genetics research component of the study include: a) Previous allogeneic bone marrow transplant b)Nonleukocyte-depleted whole blood transfusion within 120 days of genetic sample collection.

Location

Research Site

Pavia, Italy, 27100

Location

Research Site

Ravenna, Italy, 48121

Location

Research Site

Modena, Italy, 41124

Location

Research Site

Monza, Italy, 20900

Location

Research Site

Meldola, Italy, 47014

Location

Research Site

Messina, Italy, 98158

Location

Research Site

Oviedo, Spain, 33011

Location

Research Site

Sabadell(Barcelona), Spain, 08208

Arms	Assigned Interventions
Experimental: Cohort A Patients received standard radiotherapy [60 gray (Gy) ± 10% or hypofractionated BED] prior to study entry.	Drug: Durvalumab All patients will receive 1500 mg durvalumab via IV infusion q4w for up to a maximum of 12 months. Other Name: MEDI4736
Experimental: Cohort B Patients received palliative radiotherapy [40 to < 54 Gy or hypofractionated BED] prior to study entry.	Drug: Durvalumab All patients will receive 1500 mg durvalumab via IV infusion q4w for up to a maximum of 12 months. Other Name: MEDI4736

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were enrolled and received study treatment at 29 sites in 5 countries (France, Italy, Poland, Russian Federation, and Spain). The data in this report are based on study start date (first patient enrolled: 26 November 2020 till final analyses data cut-off date of 06 December 2023.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible patients who met all inclusion criteria were enrolled in the study. However, one patient was later found to have an important protocol deviation, and many other patients had protocol deviations. Study assessments followed scheduled timeline. Enrolled patients had Stage III unresectable Non-Small Cell Lung Cancer (NSCLC), an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, had been treated with radiotherapy, and were ineligible for chemotherapy.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Eligible patients who met all inclusion criteria were enrolled in the study. However, one patient was later found to have an important protocol deviation, and many other patients had protocol deviations. Study assessments followed scheduled timeline. Enrolled patients had Stage III unresectable Non-Small Cell Lung Cancer (NSCLC), an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, had been treated with radiotherapy, and were ineligible for chemotherapy.

Reporting Groups

Description

Durvalumab Cohort A: Standard radiotherapy (RT)

Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Durvaumab Cohort B: Palliative radiotherapy (RT)

Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Participant Flow: Overall Study

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)
STARTED	53	49
COMPLETED	53	49
NOT COMPLETED	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

Description

Durvalumab Cohort A: Standard radiotherapy (RT)

Durvaumab Cohort B: Palliative radiotherapy (RT)

Baseline Measures

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Total
Number of Participants [units: Participants]	53	49	102
Age Continuous [units: Years] Mean ± Standard Deviation	74.7 ± 9.18	78.8 ± 6.71	76.7 ± 8.32
Sex: Female, Male [units: Participants]
Female	15	14	29
Male	38	35	73
Race/Ethnicity, Customized [units: Participants]
White	46	45	91
Other	1	0	1
Unknown	3	1	4
Missing	3	3	6
Race/Ethnicity, Customized [units: Participants]
Hispanic or Latino	2	3	5
Not Hispanic or Latino	45	43	88
Missing	6	3	9

Outcome Measures

1. Primary Outcome Measure: Number of patients with Grade 3 and Grade 4 possibly-related adverse events (PRAEs) [ Time Frame: From first dose of durvalumab treatment until 6 months after initiation of durvalumab treatment ]

Measure Type	Primary
Measure Name	Number of patients with Grade 3 and Grade 4 possibly-related adverse events (PRAEs)
Measure Description	The safety and tolerability profile of durvalumab as defined by Grade 3 and Grade 4 PRAEs within 6 months from the initiation of durvalumab treatment. A PRAE was any TEAE with a possible relatedness to durvalumab, or where the relatedness was missing. If relatedness of a TEAE was missing at the primary DCO (30 March 2023) the TEAE was considered a PRAE.
Time Frame	From first dose of durvalumab treatment until 6 months after initiation of durvalumab treatment
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	53	49	102
Number of patients with Grade 3 and Grade 4 possibly-related adverse events (PRAEs) [units: Participants]	5	5	10

No statistical analysis provided for Number of patients with Grade 3 and Grade 4 possibly-related adverse events (PRAEs)

2. Secondary Outcome Measure: Median Progression-free survival (mPFS) [ Time Frame: From the first date of treatment until the date of objective disease progression or death or data cut-off date (36 months) ]

Measure Type	Secondary
Measure Name	Median Progression-free survival (mPFS)
Measure Description	Progression-free survival is defined as the time from the date of first dose of durvalumab until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient discontinues durvalumab or receives another anticancer therapy prior to progression according to RECIST 1.1 as assessed by the Investigator. Patients who had not progressed or died at the time of analysis were censored at the date of their last evaluable tumor assessment. If a patient progressed or died after two or more missed visits, they were censored at the date of the latest evaluable assessment prior to the missed visits.
Time Frame	From the first date of treatment until the date of objective disease progression or death or data cut-off date (36 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	53	49	102
Median Progression-free survival (mPFS) [units: Months] Median (95% Confidence Interval)	10.3 (7.49 to 16.56)	7.6 (5.55 to 11.04)	9.2 (7.39 to 11.93)

No statistical analysis provided for Median Progression-free survival (mPFS)

3. Secondary Outcome Measure: Progression-free survival at 6 months (PFS6) [ Time Frame: From the first date of treatment until the date of objective disease progression or death (6 months) ]

Measure Type	Secondary
Measure Name	Progression-free survival at 6 months (PFS6)
Measure Description	Progression-free survival is defined as the time from the date of first dose of durvalumab until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient discontinues durvalumab or receives another anticancer therapy prior to progression according to RECIST 1.1 as assessed by the Investigator. Patients who had not progressed or died at the time of analysis were censored at the date of their last evaluable tumor assessment. If a patient progressed or died after two or more missed visits, they were censored at the date of the latest evaluable assessment prior to the missed visits.
Time Frame	From the first date of treatment until the date of objective disease progression or death (6 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	53	49	102
Progression-free survival at 6 months (PFS6) [units: Percentage of patients] Number (95% Confidence Interval)	67.1 (51.96 to 78.43)	59.3 (43.38 to 72.07)	63.3 (52.62 to 72.25)

No statistical analysis provided for Progression-free survival at 6 months (PFS6)

4. Secondary Outcome Measure: Progression-free survival at 12 months (PFS12) [ Time Frame: From the first date of treatment until the date of objective disease progression or death (12 months) ]

Measure Type	Secondary
Measure Name	Progression-free survival at 12 months (PFS12)
Measure Description	Progression-free survival is defined as the time from the date of first dose of durvalumab until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient discontinues durvalumab or receives another anticancer therapy prior to progression according to RECIST 1.1 as assessed by the Investigator. Patients who had not progressed or died at the time of analysis were censored at the date of their last evaluable tumor assessment. If a patient progressed or died after two or more missed visits, they were censored at the date of the latest evaluable assessment prior to the missed visits.
Time Frame	From the first date of treatment until the date of objective disease progression or death (12 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	53	49	102
Progression-free survival at 12 months (PFS12) [units: Percentage of patients] Number (95% Confidence Interval)	46.8 (31.88 to 60.36)	31.8 (18.13 to 46.32)	39.6 (29.28 to 49.76)

No statistical analysis provided for Progression-free survival at 12 months (PFS12)

5. Secondary Outcome Measure: Median overall survival (mOS) [ Time Frame: From the first date of treatment until death or data cut-off due to any cause (36 months) ]

Measure Type	Secondary
Measure Name	Median overall survival (mOS)
Measure Description	The OS is defined as the time from the date of first dose of durvalumab until death due to any cause. Patients who were not known to have died at the time of analysis were censored at the last recorded date when they were known to have been alive.
Time Frame	From the first date of treatment until death or data cut-off due to any cause (36 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	53	49	102
Median overall survival (mOS) [units: Months] Median (95% Confidence Interval)	21.1 (11.60 to NA) ^[1]	16.8 (10.64 to NA) ^[1]	21.1 (14.75 to NA) ^[1]

No statistical analysis provided for Median overall survival (mOS)

6. Secondary Outcome Measure: Overall survival at 12 months (OS12) [ Time Frame: From the first date of treatment until death due to any cause (12 months) ]

Measure Type	Secondary
Measure Name	Overall survival at 12 months (OS12)
Measure Description	The OS is defined as the time from the date of first dose of durvalumab until death due to any cause. Patients who were not known to have died at the time of analysis were censored at the last recorded date when they were known to have been alive.
Time Frame	From the first date of treatment until death due to any cause (12 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	53	49	102
Overall survival at 12 months (OS12) [units: Percentage of patients] Number (95% Confidence Interval)	64.0 (49.01 to 75.58)	65.5 (49.87 to 77.26)	64.7 (54.21 to 73.34)

No statistical analysis provided for Overall survival at 12 months (OS12)

7. Secondary Outcome Measure: Objective response rate (ORR) [ Time Frame: From 8 weeks ±1 week after durvalumab treatment initiation and continue every 8 weeks (q8w) ±1 week through 48 weeks and every 12 weeks (q12w) ±1 week until disease progression or data cut-off (36 months) ]

Measure Type	Secondary
Measure Name	Objective response rate (ORR)
Measure Description	The ORR is the proportion (%) of patients with an overall response of complete response (CR) or partial response (PR) (confirmed by a follow-up scan at least 4 weeks after showing CR or PR) per RECIST 1.1 criteria. CR is disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to < 10 mm. PR is at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Time Frame	From 8 weeks ±1 week after durvalumab treatment initiation and continue every 8 weeks (q8w) ±1 week through 48 weeks and every 12 weeks (q12w) ±1 week until disease progression or data cut-off (36 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	53	49	102
Objective response rate (ORR) [units: Percentage of patients] Number (95% Confidence Interval)	34.0 (21.5 to 48.3)	24.5 (13.3 to 38.9)	29.4 (20.8 to 39.3)

No statistical analysis provided for Objective response rate (ORR)

8. Secondary Outcome Measure: Duration of response (DoR) [ Time Frame: From 8 weeks ±1 week after durvalumab treatment initiation and continue every 8 weeks (q8w) ±1 week through 48 weeks and every 12 weeks (q12w) ±1 week until disease progression or data cut-off (36 months) ]

Measure Type	Secondary
Measure Name	Duration of response (DoR)
Measure Description	The DoR is defined as the time from the date of first documented response (which is subsequently confirmed) until the first date of documented progression per RECIST1.1 or death in the absence of disease progression.
Time Frame	From 8 weeks ±1 week after durvalumab treatment initiation and continue every 8 weeks (q8w) ±1 week through 48 weeks and every 12 weeks (q12w) ±1 week until disease progression or data cut-off (36 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment. Number of participants analyzed and number analyzed here represents number of patients with objective response.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	18	12	30
Duration of response (DoR) [units: Weeks] Median (95% Confidence Interval)	56.9 (31.00 to NA) ^[1]	34.1 (24.29 to NA) ^[1]	56.9 (31.14 to NA) ^[1]

No statistical analysis provided for Duration of response (DoR)

9. Secondary Outcome Measure: Lung cancer mortality [ Time Frame: From date of treatment start until death due to lung cancer (36 months) ]

Measure Type	Secondary
Measure Name	Lung cancer mortality
Measure Description	The lung cancer mortality (NSCLC-related death) is assessed using the deaths which are reported as ‘NSCLC-related’ and is defined as the time (days) from the date of first dose of durvalumab until date of death due to lung cancer.
Time Frame	From date of treatment start until death due to lung cancer (36 months)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	53	49	102
Lung cancer mortality [units: Months] Median (95% Confidence Interval)	30.9 (16.92 to NA) ^[1]	NA (14.75 to NA) ^[1]	30.9 (16.82 to NA) ^[1]

No statistical analysis provided for Lung cancer mortality

10. Secondary Outcome Measure: Number of patients with events (AEs) [ Time Frame: From screening (Day -28) till data cut-off (36 months) ]

Measure Type	Secondary
Measure Name	Number of patients with events (AEs)
Measure Description	The safety and tolerability profile of durvalumab treatment, including all adverse events (AEs) was assessed.
Time Frame	From screening (Day -28) till data cut-off (36 months)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	53	49	102
Number of patients with events (AEs) [units: Participants]
Any AE	50	49	99
Any PRAE (Investigator-assessed [IA])	31	31	62
Any AE of CTCAE Grade 3 or Grade 4	20	21	41
Any AE of CTCAE Grade 3 or Grade 4, possibly related to durvalumab treatment (IA)	6	5	11
Any AE with outcome of death	5	2	7
Any AE with outcome of death, possibly related to treatment (IA)	1	0	1
Any SAE (including events with outcome of death)	23	18	41
Any SAE (including events with outcome of death), possibly related to treatment (IA)	5	3	8
Any AE leading to discontinuation of treatment	13	9	22
Any AE leading to discontinuation of treatment, possibly related to treatment (IA)	7	5	12
Any AE leading to treatment interruption	25	23	48
Any AE leading to treatment interruption, possibly related to treatment	6	7	13
Any AESI (including events with outcome of death) (IA)	25	21	46
Any AESI (including events with outcome of death), possibly related to treatment (IA)	19	14	33
Any Adverse event of potential interest (AEPI) (including events with outcome of death) (IA)	21	22	43
Any AEPI (including events with outcome of death), possibly related to treatment (IA)	14	15	29
Any imAE (IA)	27	24	51
Any imAE, possibly related to treatment (IA)	26	24	50

No statistical analysis provided for Number of patients with events (AEs)

11. Secondary Outcome Measure: Number of patients with adverse events of special interests (AESIs) [ Time Frame: From screening (Day -28) till data cut-off (36 months) ]

Measure Type	Secondary
Measure Name	Number of patients with adverse events of special interests (AESIs)
Measure Description	The safety and tolerability profile of durvalumab treatment, including all adverse events (AEs) was assessed. An AESI is an AE of scientific and medical interest specific to the understanding of durvalumab. AESIs for durvalumab include, but are not limited to, events with a potential inflammatory or immune-mediated mechanism and which may require more frequent monitoring and/or interventions such as steroids, immunosuppressants and/or hormone replacement therapy. Here, number of patients experienced AESIs are presented. Serious adverse event of special interests (SAESIs).
Time Frame	From screening (Day -28) till data cut-off (36 months)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	53	49	102
Number of patients with adverse events of special interests (AESIs) [units: Participants]
Any AESIs	25	21	46
Any AESIs of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4	4	1	5
Any SAESIs [including events with outcome = death])	4	1	5
Any AESIs with outcome = death	1	0	1
Any AESIs, causally related to treatment	19	14	33
Any AESIs of CTCAE Grade 3 or 4, causally related to treatment	4	1	5
Any SAESIs, causally related to treatment	4	1	5
Any AESIs with outcome = death, causally related to treatment	1	0	1
AESIs: Received systemic corticosteroids	5	8	13
AESIs: Received high dose steroids	4	6	10
AESIs: Received endocrine therapy	6	5	11
AESIs: Received other immunosuppressants	0	0	0
Any AESIs leading to discontinuation of durvalumab treatment	4	3	7
AESIs: Event outcome resolved	13	12	25
AESIs: Event outcome not resolved	11	9	20

No statistical analysis provided for Number of patients with adverse events of special interests (AESIs)

12. Secondary Outcome Measure: Number of patients with immune-mediated adverse events (imAEs) [ Time Frame: From screening (Day -28) till data cut-off (36 months) ]

Measure Type	Secondary
Measure Name	Number of patients with immune-mediated adverse events (imAEs)
Measure Description	The safety and tolerability profile of durvalumab treatment, including all adverse events (AEs) was assessed. An imAE is defined as an AESI that is associated with drug exposure and is consistent with an immune-mediated mechanism of action and where there is no clear alternate etiology. Here, number of patients experienced imAEs are presented. Immune-mediated serious adverse events (imSAEs)
Time Frame	From screening (Day -28) till data cut-off (36 months)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all patients who received at least one dose of durvalumab treatment.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Measured Values

	Durvalumab Cohort A: Standard radiotherapy (RT)	Durvaumab Cohort B: Palliative radiotherapy (RT)	Durvalumab total
Number of Participants Analyzed [units:participants]	53	49	102
Number of patients with immune-mediated adverse events (imAEs) [units: Participants]
Any imAEs	11	15	26
Any imAEs of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4	2	3	5
Any imSAEs [including events with outcome = death])	3	2	5
Any imAEs with outcome = death	1	0	1
Any imAEs, causally related to treatment	10	12	22
Any imAEs of CTCAE Grade 3 or 4, causally related to treatment	2	3	5
Any imSAEs, causally related to treatment	3	2	5
Any imAEs with outcome = death, causally related to treatment	1	0	1
imAEs: Received systemic corticosteroids	7	13	20
imAEs: Received high dose steroids	5	7	12
imAEs: Received endocrine therapy	6	5	11
imAEs: Received other immunosuppressants	0	0	0
Any imAEs leading to discontinuation of durvalumab treatment	3	4	7
imAEs: Event outcome resolved	5	8	13
imAEs: Event outcome not resolved	5	7	12

No statistical analysis provided for Number of patients with immune-mediated adverse events (imAEs)

Serious Adverse Events

Time Frame	From screening (Day -28) till data cut-off (36 months)
Additional Description	No text entered.

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Serious Adverse Events

Durvalumab Cohort A: Standard radiotherapy (RT)

Durvaumab Cohort B: Palliative radiotherapy (RT)

Durvalumab total

Total, serious adverse events

# participants affected / at risk

23/53 (43.40%)

18/49 (36.73%)

41/102 (40.20%)

Infections and infestations

COVID-19 pneumonia¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Infections and infestations

Device related infection¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Infections and infestations

Enterobacter sepsis¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Infections and infestations

Pneumonia¹

# participants affected / at risk

3/53 (5.66%)

2/49 (4.08%)

5/102 (4.90%)

# events

Infections and infestations

Pneumonia bacterial¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Infections and infestations

Pneumonia cytomegaloviral¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Infections and infestations

Lower respiratory tract infection¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Transitional cell carcinoma¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Endocrine disorders

Hyperthyroidism¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Nervous system disorders

Cerebral ischaemia¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Nervous system disorders

Ischaemic stroke¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Nervous system disorders

Syncope¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Cardiac disorders

Atrial fibrillation¹

# participants affected / at risk

2/53 (3.77%)

0/49 (0.00%)

2/102 (1.96%)

# events

Cardiac disorders

Cardiac failure¹

# participants affected / at risk

1/53 (1.89%)

4/49 (8.16%)

5/102 (4.90%)

# events

Cardiac disorders

Left ventricular failure¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Cardiac disorders

Myocarditis¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Vascular disorders

Circulatory collapse¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Vascular disorders

Hypotension¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Vascular disorders

Hypovolaemic shock¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Respiratory, thoracic and mediastinal disorders

Aspiration¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹

# participants affected / at risk

1/53 (1.89%)

1/49 (2.04%)

1/102 (0.98%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary haemorrhage¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹

# participants affected / at risk

1/53 (1.89%)

1/49 (2.04%)

2/102 (1.96%)

# events

Gastrointestinal disorders

Dysphagia¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Hepatobiliary disorders

Hepatotoxicity¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Skin and subcutaneous tissue disorders

Dermatomyositis¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Renal and urinary disorders

Immune-mediated nephritis¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

General disorders

Asthenia¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

General disorders

Death¹

# participants affected / at risk

1/53 (1.89%)

1/49 (2.04%)

2/102 (1.96%)

# events

General disorders

General physical health deterioration¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

General disorders

Pyrexia¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Investigations

Aspartate aminotransferase increased¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Injury, poisoning and procedural complications

Injury¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Injury, poisoning and procedural complications

Subdural haemorrhage¹

# participants affected / at risk

1/53 (1.89%)

0/49 (0.00%)

1/102 (0.98%)

# events

Respiratory, thoracic and mediastinal disorders

Organising pneumonia¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹

# participants affected / at risk

0/53 (0.00%)

1/49 (2.04%)

1/102 (0.98%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 26.1

Other Adverse Events

Time Frame	From screening (Day -28) till data cut-off (36 months)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	2.5%

Reporting Groups

	Description
Durvalumab Cohort A: Standard radiotherapy (RT)	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated bioequivalent dose (BED)] before study entry were administered a fixed dose of 1500 mg of durvalumab via intravenous (IV) infusion every 4 weeks (q4w) for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the response evaluation criteria in solid tumors version (RECIST 1.1), unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvaumab Cohort B: Palliative radiotherapy (RT)	Patients who received palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
Durvalumab total	Patients who received standard RT [60 gray (GY) ± 10% or hypofractionated BED)] or palliative RT [40 to < 54 Gy or hypofractionated BED] before study entry were administered a fixed dose of 1500 mg of durvalumab via IV infusion q4w for a duration of 12 months (up to 13 doses/cycles), or until clinical progression or radiological progression defined by the RECIST 1.1, unless there was unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Other Adverse Events

Durvalumab Cohort A: Standard radiotherapy (RT)

Durvaumab Cohort B: Palliative radiotherapy (RT)

Durvalumab total

Total, other (not including serious) adverse events

# participants affected / at risk

47/53 (88.68%)

45/49 (91.84%)

92/102 (90.20%)

Infections and infestations

COVID-19¹

# participants affected / at risk

6/53 (11.32%)

3/49 (6.12%)

9/102 (8.82%)

# events

Infections and infestations

Herpes zoster¹

# participants affected / at risk

2/53 (3.77%)

0/49 (0.00%)

2/102 (1.96%)

# events

Infections and infestations

Pneumonia¹

# participants affected / at risk

3/53 (5.66%)

3/49 (6.12%)

6/102 (5.88%)

# events

Blood and lymphatic system disorders

Anaemia¹

# participants affected / at risk

13/53 (24.53%)

6/49 (12.24%)

19/102 (18.63%)

# events

Blood and lymphatic system disorders

Leukocytosis¹

# participants affected / at risk

3/53 (5.66%)

2/49 (4.08%)

5/102 (4.90%)

# events

Blood and lymphatic system disorders

Lymphopenia¹

# participants affected / at risk

2/53 (3.77%)

2/49 (4.08%)

4/102 (3.92%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹

# participants affected / at risk

2/53 (3.77%)

0/49 (0.00%)

2/102 (1.96%)

# events

Blood and lymphatic system disorders

Thrombocytosis¹

# participants affected / at risk

2/53 (3.77%)

0/49 (0.00%)

2/102 (1.96%)

# events

Endocrine disorders

Hyperthyroidism¹

# participants affected / at risk

6/53 (11.32%)

5/49 (10.20%)

11/102 (10.78%)

# events

Endocrine disorders

Hypothyroidism¹

# participants affected / at risk

9/53 (16.98%)

6/49 (12.24%)

15/102 (14.71%)

# events

Endocrine disorders

Thyroiditis¹

# participants affected / at risk

2/53 (3.77%)

0/49 (0.00%)

2/102 (1.96%)

# events

Metabolism and nutrition disorders

Decreased appetite¹

# participants affected / at risk

8/53 (15.09%)

6/49 (12.24%)

14/102 (13.73%)

# events

Metabolism and nutrition disorders

Hyperkalaemia¹

# participants affected / at risk

2/53 (3.77%)

4/49 (8.16%)

6/102 (5.88%)

# events

Psychiatric disorders

Insomnia¹

# participants affected / at risk

0/53 (0.00%)

2/49 (4.08%)

2/102 (1.96%)

# events

Nervous system disorders

Dizziness¹

# participants affected / at risk

2/53 (3.77%)

1/49 (2.04%)

3/102 (2.94%)

# events

Nervous system disorders

Headache¹

# participants affected / at risk

1/53 (1.89%)

2/49 (4.08%)

3/102 (2.94%)

# events

Eye disorders

Periorbital oedema¹

# participants affected / at risk

0/53 (0.00%)

2/49 (4.08%)

2/102 (1.96%)

# events

Vascular disorders

Hypertension¹

# participants affected / at risk

0/53 (0.00%)

5/49 (10.20%)

5/102 (4.90%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹

# participants affected / at risk

2/53 (3.77%)

4/49 (8.16%)

6/102 (5.88%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹

# participants affected / at risk

9/53 (16.98%)

12/49 (24.49%)

21/102 (20.59%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹

# participants affected / at risk

11/53 (20.75%)

8/49 (16.33%)

19/102 (18.63%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea exertional¹

# participants affected / at risk

3/53 (5.66%)

3/49 (6.12%)

6/102 (5.88%)

# events

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹

# participants affected / at risk

2/53 (3.77%)

3/49 (6.12%)

5/102 (4.90%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹

# participants affected / at risk

3/53 (5.66%)

4/49 (8.16%)

7/102 (6.86%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary fibrosis¹

# participants affected / at risk

2/53 (3.77%)

0/49 (0.00%)

2/102 (1.96%)

# events

Gastrointestinal disorders

Abdominal pain upper¹

# participants affected / at risk

1/53 (1.89%)

2/49 (4.08%)

3/102 (2.94%)

# events

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

3/53 (5.66%)

10/49 (20.41%)

13/102 (12.75%)

# events

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

3/53 (5.66%)

4/49 (8.16%)

7/102 (6.86%)

# events

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

0/53 (0.00%)

4/49 (8.16%)

4/102 (3.92%)

# events

Hepatobiliary disorders

Hepatotoxicity¹

# participants affected / at risk

0/53 (0.00%)

2/49 (4.08%)

2/102 (1.96%)

# events

Skin and subcutaneous tissue disorders

Dry skin¹

# participants affected / at risk

2/53 (3.77%)

0/49 (0.00%)

2/102 (1.96%)

# events

Skin and subcutaneous tissue disorders

Erythema¹

# participants affected / at risk

0/53 (0.00%)

2/49 (4.08%)

2/102 (1.96%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹

# participants affected / at risk

5/53 (9.43%)

8/49 (16.33%)

13/102 (12.75%)

# events

Skin and subcutaneous tissue disorders

Rash¹

# participants affected / at risk

2/53 (3.77%)

1/49 (2.04%)

3/102 (2.94%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹

# participants affected / at risk

8/53 (15.09%)

6/49 (12.24%)

14/102 (13.73%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹

# participants affected / at risk

5/53 (9.43%)

5/49 (10.20%)

10/102 (9.80%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹

# participants affected / at risk

1/53 (1.89%)

2/49 (4.08%)

3/102 (2.94%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹

# participants affected / at risk

1/53 (1.89%)

2/49 (4.08%)

3/102 (2.94%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹

# participants affected / at risk

1/53 (1.89%)

2/49 (4.08%)

3/102 (2.94%)

# events

Musculoskeletal and connective tissue disorders

Spinal pain¹

# participants affected / at risk

0/53 (0.00%)

2/49 (4.08%)

2/102 (1.96%)

# events

Renal and urinary disorders

Acute kidney injury¹

# participants affected / at risk

2/53 (3.77%)

1/49 (2.04%)

3/102 (2.94%)

# events

Renal and urinary disorders

Urinary incontinence¹

# participants affected / at risk

0/53 (0.00%)

2/49 (4.08%)

2/102 (1.96%)

# events

General disorders

Asthenia¹

# participants affected / at risk

13/53 (24.53%)

8/49 (16.33%)

21/102 (20.59%)

# events

General disorders

Fatigue¹

# participants affected / at risk

1/53 (1.89%)

10/49 (20.41%)

11/102 (10.78%)

# events

General disorders

Oedema peripheral¹

# participants affected / at risk

3/53 (5.66%)

5/49 (10.20%)

8/102 (7.84%)

# events

General disorders

Pyrexia¹

# participants affected / at risk

8/53 (15.09%)

8/49 (16.33%)

16/102 (15.69%)

# events

Investigations

Alanine aminotransferase increased¹

# participants affected / at risk

4/53 (7.55%)

3/49 (6.12%)

7/102 (6.86%)

# events

Investigations

Amylase increased¹

# participants affected / at risk

3/53 (5.66%)

2/49 (4.08%)

5/102 (4.90%)

# events

Investigations

Aspartate aminotransferase increased¹

# participants affected / at risk

3/53 (5.66%)

1/49 (2.04%)

4/102 (3.92%)

# events

Investigations

Blood alkaline phosphatase increased¹

# participants affected / at risk

3/53 (5.66%)

2/49 (4.08%)

5/102 (4.90%)

# events

Investigations

Blood creatinine increased¹

# participants affected / at risk

2/53 (3.77%)

4/49 (8.16%)

6/102 (5.88%)

# events

Investigations

Blood lactate dehydrogenase increased¹

# participants affected / at risk

3/53 (5.66%)

1/49 (2.04%)

4/102 (3.92%)

# events

Investigations

Blood thyroid stimulating hormone decreased¹

# participants affected / at risk

2/53 (3.77%)

0/49 (0.00%)

2/102 (1.96%)

# events

Investigations

Blood urea increased¹

# participants affected / at risk

3/53 (5.66%)

1/49 (2.04%)

4/102 (3.92%)

# events

Investigations

Blood uric acid increased¹

# participants affected / at risk

2/53 (3.77%)

1/49 (2.04%)

3/102 (2.94%)

# events

Investigations

C-reactive protein increased¹

# participants affected / at risk

4/53 (7.55%)

1/49 (2.04%)

5/102 (4.90%)

# events

Investigations

Gamma-glutamyltransferase increased¹

# participants affected / at risk

3/53 (5.66%)

2/49 (4.08%)

5/102 (4.90%)

# events

Investigations

Lipase increased¹

# participants affected / at risk

1/53 (1.89%)

2/49 (4.08%)

3/102 (2.94%)

# events

Investigations

Neutrophil count increased¹

# participants affected / at risk

4/53 (7.55%)

0/49 (0.00%)

4/102 (3.92%)

# events

Investigations

Weight decreased¹

# participants affected / at risk

2/53 (3.77%)

0/49 (0.00%)

2/102 (1.96%)

# events

Injury, poisoning and procedural complications

Radiation pneumonitis¹

# participants affected / at risk

1/53 (1.89%)

2/49 (4.08%)

3/102 (2.94%)

# events

Injury, poisoning and procedural complications

Spinal compression fracture¹

# participants affected / at risk

0/53 (0.00%)

2/49 (4.08%)

2/102 (1.96%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹

# participants affected / at risk

2/53 (3.77%)

0/49 (0.00%)

2/102 (1.96%)

# events

Gastrointestinal disorders

Stomatitis¹

# participants affected / at risk

1/53 (1.89%)

2/49 (4.08%)

3/102 (2.94%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹

# participants affected / at risk

0/53 (0.00%)

2/49 (4.08%)

2/102 (1.96%)

# events

Injury, poisoning and procedural complications

Fall¹

# participants affected / at risk

0/53 (0.00%)

2/49 (4.08%)

2/102 (1.96%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 26.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Download
CSP Redacted
Download
SAP Redacted
Download
CSR synopsis Redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Dr Andrea Riccardo Filippi

Fondazione IRCCS Policlinico San Matteo

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

CSP Redacted

SAP Redacted

CSR synopsis Redacted

Trial Results Summaries