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Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN) (CASPIAN)

Primary Purpose

Small Cell Lung Carcinoma Extensive Disease

Status

Active

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Durvalumab

Tremelimumab

Carboplatin

Cisplatin

Etoposide

About this trial

This is an interventional treatment trial for Small Cell Lung Carcinoma Extensive Disease focused on measuring Carcinoma, Small Cell Lung, Oat Cell Carcinoma of Lung, Oat Cell Lung Cancer, Small Cell Cancer Of The Lung, Small Cell Lung Cancer

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Histologically or cytologically documented extensive disease. Brain metastases; must be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment.
Suitable to receive a platinum-based chemotherapy regimen as 1st line treatment.
Life expectancy ≥12 weeks at Day 1.
ECOG 0 or 1 at enrolment.
No prior exposure to immune-mediated therapy excluding therapeutic anticancer vaccines.

Exclusion criteria:

Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy (except paliative care outside of the chest).
Paraneoplastic syndrome of autoimmune nature, requiring systemic treatment or clinical symptomatology suggesting worsening of PNS
Active infection including tuberculosis, HIV, hepatitis B anc C
Active or prior documented autoimmune or inflammatory disorders
Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Arm 1

Arm 2

Arm 3

Arm Description

durvalumab+tremelimumab+EP (carboplatin or cisplatin + etoposide)

durvalumab+EP (carboplatin or cisplatin + etoposide)

EP (carboplatin or cisplatin + etoposide)

Outcomes

Primary Outcome Measures

Overall Survival (OS) in the Global Cohort; Assessed at Global Cohort Interim Analysis; D + EP Compared With EP

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An interim analysis of OS in the global cohort was pre-specified after approximately 318 OS events occurred each between the D + EP and EP groups (60% maturity), and between the D + T + EP and EP groups (60% maturity). At the global cohort interim analysis DCO (11 March 2019), comparison of OS in the D + EP versus (vs) EP groups had crossed the pre-specified boundary. Since these results were considered final in terms of formal statistical testing, they are presented here as a primary outcome measure. Analysis of OS for D + EP vs EP and for D + T + EP vs EP at the time of the global cohort final analysis is presented separately in the subsequent primary outcome measure.

OS in the Global Cohort; Assessed at Global Cohort Final Analysis; D + EP Compared With EP and D + T + EP Compared With EP

OS in the China Cohort; Assessed at China Cohort First Analysis; D + EP Compared With EP

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + EP vs EP in the China cohort was pre-specified at approximately 60% maturity (to ensure a similar maturity to the interim analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP at the China cohort first analysis DCO (06 January 2020), and is comparable in terms of maturity with the interim analysis of OS for D + EP vs EP in the Global cohort. Analysis of OS for D + EP vs EP and for D + T + EP vs EP at the time of the China cohort second analysis is presented separately in the subsequent primary outcome measure.

OS in the China Cohort; Assessed at China Cohort Second Analysis; D + EP Compared With EP and D + T + EP Compared With EP

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + T + EP vs EP in the China cohort was pre-specified at approximately 80% maturity (to ensure a similar maturity to the final analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP and D + T + EP vs EP at the time of the China cohort second analysis DCO (02 November 2020), and is comparable in terms of maturity with the final analysis of OS for D + EP vs EP and D + T + EP vs EP in the Global cohort. Analysis of D + EP vs EP at the China cohort first analysis DCO is presented in the previous primary outcome measure. Analysis of D + T + EP vs D + EP (China cohort second analysis) is presented as a secondary outcome measure.

Secondary Outcome Measures

OS in the Global Cohort; D + T + EP Compared With D + EP

OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This secondary outcome measure presents OS for the analysis of D + T + EP vs D + EP in the global cohort. The alternative treatment comparisons in the global cohort were performed as primary outcome measures.

Progression-Free Survival (PFS) in the Global Cohort

PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1] using Investigator assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (ie, PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir) and an absolute increase of ≥5 millimeters (mm) for the sum from nadir. For evaluation of non-target lesions (NTLs), PD was defined as unequivocal progression of existing NTLs. Median PFS was calculated using the Kaplan-Meier technique.

Objective Response Rate (ORR) in the Global Cohort

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of patients with at least 1 visit response of Complete Response (CR) or Partial Response (PR). CR was defined as disappearance of all TLs since baseline (any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm) or disappearance of all NTLs since baseline (all lymph nodes must be non-pathological in size [<10 mm short axis]). PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters).

Percentage of Patients Alive and Progression Free at 6 Months (APF6) in the Global Cohort

The APF6 was defined as the percentage of patients who were alive and progression free at 6 months from randomization (ie, PFS rate at 6 months). PFS was calculated using the Kaplan-Meier technique.

Percentage of Patients Alive and Progression Free at 12 Months (APF12) in the Global Cohort

The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months). PFS was calculated using the Kaplan-Meier technique.

Percentage of Patients Alive at 18 Months (OS18) in the Global Cohort

OS18 was defined as the percentage of patients who were alive at 18 months after randomization per the Kaplan-Meier estimate of OS at 18 months.

Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations in the Global Cohort

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of durvalumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.

PK of Tremelimumab; Peak and Trough Serum Concentrations in the Global Cohort

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of tremelimumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.

Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab in the Global Cohort

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of neutralizing antibody (nAb) was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to durvalumab for each indicated category.

Number of Patients With ADA Response to Tremelimumab in the Global Cohort

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA (or ADA incidence) was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to tremelimumab for each indicated category.

Time to Deterioration of Health-Related Quality of Life (HRQoL) and Patient Reported Outcome (PRO) Symptoms, Assessed Using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) in the Global Cohort

The EORTC QLQ-Core 30 version 3 (QLQ-C30 v3) was included for assessing HRQoL. It assesses HRQoL/health status through 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), and a global health and QoL scale. 6 single-item symptom measures are also included: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Scores from 0 to 100 were derived for each of the 15 domains, with higher scores representing greater functioning, greater HRQoL, or greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.

Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13) in the Global Cohort

The EORTC QLQ-LC13 is a disease-specific 13-item self-administered questionnaire for lung cancer, to be used in conjunction with the EORTC QLQ-C30. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and side effects from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores from 0 to 100 were derived for each symptom item, with higher scores representing greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (an increase in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.

Change From Baseline in Primary PRO Symptoms as Assessed by EORTC QLQ in the Global Cohort; D + T + EP Compared With EP

A mixed model repeated measures (MMRM) analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + T + EP vs P. Analysis of D + EP vs EP is presented in a separate outcome measure.

Change From Baseline in Primary Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the Global Cohort; D + EP Compared With EP

A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + EP vs EP. Analysis of D + T + EP vs EP is presented in a separate outcome measure.

OS in the China Cohort; D + T + EP Compared With D + EP

OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This secondary outcome measure presents OS for the analysis of D + T + EP vs D + EP at the China cohort second analysis DCO (02 November 2020). The alternative treatment comparisons were performed as primary outcome measures.

PFS in the China Cohort

PFS (per RECIST 1.1 using Investigator assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (ie, PD) was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) and an absolute increase of ≥5 mm for the sum from nadir. For evaluation of NTLs, PD was defined as unequivocal progression of existing NTLs. Median PFS was calculated using the Kaplan-Meier technique.

ORR in the China Cohort

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of patients with at least 1 visit response of CR or PR. CR was defined as disappearance of all TLs since baseline (any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm) or disappearance of all NTLs since baseline (all lymph nodes must be non-pathological in size [<10 mm short axis]). PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters).

APF6 in the China Cohort

The APF6 was defined as the percentage of patients who were alive and progression free at 6 months from randomization (ie, PFS rate at 6 months). PFS was calculated using the Kaplan-Meier technique.

APF12 in the China Cohort

OS18 in the China Cohort

OS18 was defined as the percentage of patients who were alive at 18 months after randomization per the Kaplan-Meier estimate of OS at 18 months.

PK of Durvalumab; Peak and Trough Serum Concentrations in the China Cohort

PK of Tremelimumab; Peak and Trough Serum Concentrations in the China Cohort

Number of Patients With ADA Response to Durvalumab in the China Cohort

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to durvalumab for each indicated category.

Number of Patients With ADA Response to Tremelimumab in the China Cohort

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA (or ADA incidence) was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to tremelimumab for each indicated category.

Time to Deterioration of HRQoL and PRO Symptoms, Assessed Using EORTC QLQ in the China Cohort

The EORTC QLQ-C30 v3 was included for assessing HRQoL. It assesses HRQoL/health status through 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), and a global health and QoL scale. 6 single-item symptom measures are also included: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Scores from 0 to 100 were derived for each of the 15 domains, with higher scores representing greater functioning, greater HRQoL, or greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.

Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-LC13 in the China Cohort

Change From Baseline in Primary PRO Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the China Cohort; D + T + EP Compared With EP

A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + T + EP vs EP. Analysis of D + EP vs EP is presented in a separate outcome measure.

Change From Baseline in Primary Symptoms as Assessed by EORTC QLQ in the China Cohort; D + EP Compared With EP

Full Information

NCT ID

NCT03043872

First Posted

January 18, 2017

Last Updated

October 23, 2023

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT03043872

Brief Title

Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN)

Acronym

CASPIAN

Official Title

A Phase III, Randomized, Multicenter,Open-Label, Comparative Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination With Platinum-Based Chemotherapy for the First-Line Treatment in Patients With Extensive Disease Small-Cell Lung Cancer (SCLC) (CASPIAN)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 27, 2017 (Actual)

Primary Completion Date

January 27, 2020 (Actual)

Study Completion Date

December 29, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a phase III, randomized, open-label, multicenter, global study to determine the efficacy and safety of combining durvalumab ± tremelimumab with platinum based chemotherapy (EP) followed by durvalumab ± tremelimumab maintenance therapy versus EP alone as first-line treatment in patients with extensive-stage small-cell lung cancer

Detailed Description

Primary objective of this study is to assess the efficacy of durvalumab + tremelimumab + EP treatment compared with EP and the efficacy of durvalumab + EP treatment compared with EP in terms of OS. All patients will be randomized in a 1:1:1 ratio in a stratified manner according to the planned platinum-based therapy for Cycle 1 (cisplatin or carboplatin) to receive treatment with durvalumab + tremelimumab + EP (Arm 1), durvalumab + EP (Arm 2), or standard of care- EP (Arm 3). Arm 1 and Arm 2 patients receive the treatment until confirmed disease progression while Arm 3 patients receive up to 6 cycles of EP and prophylactic cranial irradiation if clinically indicated, at the Investigators' discretion.Patients who have discontinued treatment due to toxicity or symptomatic deterioration, clinical progression, or who have commenced subsequent anticancer therapy will be followed up until confirmed disease progression and for survival. Targeted population are adult patients (aged ≥18 years) with histologically or cytologically documented extensive disease (American Joint Committee on Cancer Stage (7th edition) IV SCLC [T any, N any,M1 a/b]), or T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan. Patients must have WHO/ECOG performance status of 0 or 1. Tumor assessments will be performed at Screening as baseline with follow-up at Week 6 ±1 week from the date of randomization, at Week 12 ±1 week from the date of randomization, and then every 8 weeks ±1 week until confirmed objective disease progression. An independent data monitoring committee (IDMC) comprised of independent experts will be convened to confirm the safety and tolerability of the proposed dose and schedule of durvalumab ± tremelimumab in combination with platinum based chemotherapy at two early stages of enrolment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Small Cell Lung Carcinoma Extensive Disease

Keywords

Carcinoma, Small Cell Lung, Oat Cell Carcinoma of Lung, Oat Cell Lung Cancer, Small Cell Cancer Of The Lung, Small Cell Lung Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

987 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Arm Description

durvalumab+tremelimumab+EP (carboplatin or cisplatin + etoposide)

Arm Title

Arm 2

Arm Type

Experimental

Arm Description

durvalumab+EP (carboplatin or cisplatin + etoposide)

Arm Title

Arm 3

Arm Type

Active Comparator

Arm Description

EP (carboplatin or cisplatin + etoposide)

Intervention Type

Drug

Intervention Name(s)

Durvalumab

Intervention Description

IV infusions every 3 weeks for 12 weeks (4 cycles) and every 4 weeks thereafter until PD or other discontinuation criteria.

Intervention Type

Drug

Intervention Name(s)

Tremelimumab

Intervention Description

IV infusions every 3 weeks for 12 weeks(4 cycles). An additional dose of tremelimumab will be administered in the week 16.

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

up to 4 cycles every 3 weeks in Arm 1 and 2, up to 6 cycles every 3 weeks in Arm 3

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

up to 4 cycles every 3 weeks in Arm 1 and 2, up to 6 cycles every 3 weeks in Arm 3

Intervention Type

Drug

Intervention Name(s)

Etoposide

Intervention Description

up to 4 cycles every 3 weeks in Arm 1 and 2, up to 6 cycles every 3 weeks in Arm 3

Primary Outcome Measure Information:

Title

Overall Survival (OS) in the Global Cohort; Assessed at Global Cohort Interim Analysis; D + EP Compared With EP

Description

Time Frame

From baseline until death due to any cause. Assessed until global cohort interim analysis DCO (maximum of approximately 23 months).

Title

OS in the Global Cohort; Assessed at Global Cohort Final Analysis; D + EP Compared With EP and D + T + EP Compared With EP

Description

Time Frame

From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Title

OS in the China Cohort; Assessed at China Cohort First Analysis; D + EP Compared With EP

Description

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + EP vs EP in the China cohort was pre-specified at approximately 60% maturity (to ensure a similar maturity to the interim analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP at the China cohort first analysis DCO (06 January 2020), and is comparable in terms of maturity with the interim analysis of OS for D + EP vs EP in the Global cohort. Analysis of OS for D + EP vs EP and for D + T + EP vs EP at the time of the China cohort second analysis is presented separately in the subsequent primary outcome measure.

Time Frame

From baseline until death due to any cause. Assessed until China cohort first analysis DCO (maximum of approximately 19 months).

Title

OS in the China Cohort; Assessed at China Cohort Second Analysis; D + EP Compared With EP and D + T + EP Compared With EP

Description

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + T + EP vs EP in the China cohort was pre-specified at approximately 80% maturity (to ensure a similar maturity to the final analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP and D + T + EP vs EP at the time of the China cohort second analysis DCO (02 November 2020), and is comparable in terms of maturity with the final analysis of OS for D + EP vs EP and D + T + EP vs EP in the Global cohort. Analysis of D + EP vs EP at the China cohort first analysis DCO is presented in the previous primary outcome measure. Analysis of D + T + EP vs D + EP (China cohort second analysis) is presented as a secondary outcome measure.

Time Frame

From baseline until death due to any cause. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Secondary Outcome Measure Information:

Title

OS in the Global Cohort; D + T + EP Compared With D + EP

Description

Time Frame

From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Title

Progression-Free Survival (PFS) in the Global Cohort

Description

Time Frame

Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Title

Objective Response Rate (ORR) in the Global Cohort

Description

Time Frame

Title

Percentage of Patients Alive and Progression Free at 6 Months (APF6) in the Global Cohort

Description

The APF6 was defined as the percentage of patients who were alive and progression free at 6 months from randomization (ie, PFS rate at 6 months). PFS was calculated using the Kaplan-Meier technique.

Time Frame

Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 6 months post-randomization.

Title

Percentage of Patients Alive and Progression Free at 12 Months (APF12) in the Global Cohort

Description

Time Frame

Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 12 months post-randomization.

Title

Percentage of Patients Alive at 18 Months (OS18) in the Global Cohort

Description

OS18 was defined as the percentage of patients who were alive at 18 months after randomization per the Kaplan-Meier estimate of OS at 18 months.

Time Frame

At 18 months post-randomization. Assessed at the global cohort final analysis DCO (27 January 2020).

Title

Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations in the Global Cohort

Description

Time Frame

Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the global cohort final analysis DCO (27 January 2020).

Title

PK of Tremelimumab; Peak and Trough Serum Concentrations in the Global Cohort

Description

Time Frame

Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the global cohort final analysis DCO (27 January 2020).

Title

Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab in the Global Cohort

Description

Time Frame

Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, durvalumab). Assessed at the global cohort final analysis DCO (27 January 2020).

Title

Number of Patients With ADA Response to Tremelimumab in the Global Cohort

Description

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA (or ADA incidence) was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to tremelimumab for each indicated category.

Time Frame

Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, tremelimumab). Assessed at the global cohort final analysis DCO (27 January 2020).

Title

Description

Time Frame

At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Title

Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13) in the Global Cohort

Description

Time Frame

Title

Change From Baseline in Primary PRO Symptoms as Assessed by EORTC QLQ in the Global Cohort; D + T + EP Compared With EP

Description

Time Frame

At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

Title

Change From Baseline in Primary Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the Global Cohort; D + EP Compared With EP

Description

Time Frame

At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

Title

OS in the China Cohort; D + T + EP Compared With D + EP

Description

OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This secondary outcome measure presents OS for the analysis of D + T + EP vs D + EP at the China cohort second analysis DCO (02 November 2020). The alternative treatment comparisons were performed as primary outcome measures.

Time Frame

From baseline until death due to any cause. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Title

PFS in the China Cohort

Description

Time Frame

Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Title

ORR in the China Cohort

Description

Time Frame

Title

APF6 in the China Cohort

Description

The APF6 was defined as the percentage of patients who were alive and progression free at 6 months from randomization (ie, PFS rate at 6 months). PFS was calculated using the Kaplan-Meier technique.

Time Frame

Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 6 months post-randomization.

Title

APF12 in the China Cohort

Description

Time Frame

Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 12 months post-randomization.

Title

OS18 in the China Cohort

Description

OS18 was defined as the percentage of patients who were alive at 18 months after randomization per the Kaplan-Meier estimate of OS at 18 months.

Time Frame

At 18 months post-randomization. Assessed at the China cohort second analysis DCO (02 November 2020).

Title

PK of Durvalumab; Peak and Trough Serum Concentrations in the China Cohort

Description

Time Frame

Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the China cohort second analysis DCO (02 November 2020).

Title

PK of Tremelimumab; Peak and Trough Serum Concentrations in the China Cohort

Description

Time Frame

Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the China cohort second analysis DCO (02 November 2020).

Title

Number of Patients With ADA Response to Durvalumab in the China Cohort

Description

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to durvalumab for each indicated category.

Time Frame

Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, durvalumab). Assessed at the China cohort second analysis DCO (02 November 2020).

Title

Number of Patients With ADA Response to Tremelimumab in the China Cohort

Description

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA (or ADA incidence) was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to tremelimumab for each indicated category.

Time Frame

Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, tremelimumab). Assessed at the China cohort second analysis DCO (02 November 2020).

Title

Time to Deterioration of HRQoL and PRO Symptoms, Assessed Using EORTC QLQ in the China Cohort

Description

Time Frame

At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Title

Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-LC13 in the China Cohort

Description

Time Frame

At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Title

Change From Baseline in Primary PRO Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the China Cohort; D + T + EP Compared With EP

Description

A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + T + EP vs EP. Analysis of D + EP vs EP is presented in a separate outcome measure.

Time Frame

At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

Title

Change From Baseline in Primary Symptoms as Assessed by EORTC QLQ in the China Cohort; D + EP Compared With EP

Description

Time Frame

At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

130 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Histologically or cytologically documented extensive disease. Brain metastases; must be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment. Suitable to receive a platinum-based chemotherapy regimen as 1st line treatment. Life expectancy ≥12 weeks at Day 1. ECOG 0 or 1 at enrolment. No prior exposure to immune-mediated therapy excluding therapeutic anticancer vaccines. Exclusion criteria: Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy (except paliative care outside of the chest). Paraneoplastic syndrome of autoimmune nature, requiring systemic treatment or clinical symptomatology suggesting worsening of PNS Active infection including tuberculosis, HIV, hepatitis B anc C Active or prior documented autoimmune or inflammatory disorders Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Haiyi Jiang, M.D.

Organizational Affiliation

AstraZeneca

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35235

Country

United States

Facility Name

Research Site

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85259

Country

United States

Facility Name

Research Site

City

Rogers

State/Province

Arkansas

ZIP/Postal Code

72758

Country

United States

Facility Name

Research Site

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Facility Name

Research Site

City

Athens

State/Province

Georgia

ZIP/Postal Code

30607

Country

United States

Facility Name

Research Site

City

Fort Wayne

State/Province

Indiana

ZIP/Postal Code

46804

Country

United States

Facility Name

Research Site

City

Muncie

State/Province

Indiana

ZIP/Postal Code

47303

Country

United States

Facility Name

Research Site

City

Leawood

State/Province

Kansas

ZIP/Postal Code

66209

Country

United States

Facility Name

Research Site

City

Wichita

State/Province

Kansas

ZIP/Postal Code

67214

Country

United States

Facility Name

Research Site

City

Paducah

State/Province

Kentucky

ZIP/Postal Code

42003

Country

United States

Facility Name

Research Site

City

Grand Rapids

State/Province

Michigan

ZIP/Postal Code

49503

Country

United States

Facility Name

Research Site

City

Mineola

State/Province

New York

ZIP/Postal Code

11501

Country

United States

Facility Name

Research Site

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

Facility Name

Research Site

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43219

Country

United States

Facility Name

Research Site

City

Harrisburg

State/Province

Pennsylvania

ZIP/Postal Code

17109

Country

United States

Facility Name

Research Site

City

Sioux Falls

State/Province

South Dakota

ZIP/Postal Code

57104

Country

United States

Facility Name

Research Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Research Site

City

Kennewick

State/Province

Washington

ZIP/Postal Code

99336

Country

United States

Facility Name

Research Site

City

Buenos Aires

ZIP/Postal Code

C1118AAT

Country

Argentina

Facility Name

Research Site

City

Ciudad de Buenos Aires

ZIP/Postal Code

C1426

Country

Argentina

Facility Name

Research Site

City

Mar del Plata

ZIP/Postal Code

7600

Country

Argentina

Facility Name

Research Site

City

Rosario

ZIP/Postal Code

2000

Country

Argentina

Facility Name

Research Site

City

San Miguel de Tucuman

ZIP/Postal Code

T4000IAK

Country

Argentina

Facility Name

Research Site

City

Linz

ZIP/Postal Code

4021

Country

Austria

Facility Name

Research Site

City

Salzburg

ZIP/Postal Code

5020

Country

Austria

Facility Name

Research Site

City

Wien

ZIP/Postal Code

1140

Country

Austria

Facility Name

Research Site

City

Wien

ZIP/Postal Code

1210

Country

Austria

Facility Name

Research Site

City

Barretos

ZIP/Postal Code

14784-400

Country

Brazil

Facility Name

Research Site

City

Curitiba

ZIP/Postal Code

81520-060

Country

Brazil

Facility Name

Research Site

City

Passo Fundo

ZIP/Postal Code

99010 260

Country

Brazil

Facility Name

Research Site

City

Porto Alegre

ZIP/Postal Code

91350-200

Country

Brazil

Facility Name

Research Site

City

Ribeirão Preto

ZIP/Postal Code

14048-900

Country

Brazil

Facility Name

Research Site

City

Rio de Janeiro

ZIP/Postal Code

22793-080

Country

Brazil

Facility Name

Research Site

City

Salvador

ZIP/Postal Code

41.950-610

Country

Brazil

Facility Name

Research Site

City

Santo André

ZIP/Postal Code

09060-650

Country

Brazil

Facility Name

Research Site

City

São José do Rio Preto

ZIP/Postal Code

15090-000

Country

Brazil

Facility Name

Research Site

City

São Paulo

ZIP/Postal Code

03102-002

Country

Brazil

Facility Name

Research Site

City

Panagyurishte

ZIP/Postal Code

4500

Country

Bulgaria

Facility Name

Research Site

City

Plovdiv

ZIP/Postal Code

4000

Country

Bulgaria

Facility Name

Research Site

City

Plovdiv

ZIP/Postal Code

4004

Country

Bulgaria

Facility Name

Research Site

City

Sofia

ZIP/Postal Code

1330

Country

Bulgaria

Facility Name

Research Site

City

Sofia

ZIP/Postal Code

1431

Country

Bulgaria

Facility Name

Research Site

City

Sofia

ZIP/Postal Code

1618

Country

Bulgaria

Facility Name

Research Site

City

Sofia

ZIP/Postal Code

1784

Country

Bulgaria

Facility Name

Research Site

City

Varna

ZIP/Postal Code

9010

Country

Bulgaria

Facility Name

Research Site

City

Beijing

ZIP/Postal Code

100142

Country

China

Facility Name

Research Site

City

Beijing

ZIP/Postal Code

100730

Country

China

Facility Name

Research Site

City

Beijing

ZIP/Postal Code

100853

Country

China

Facility Name

Research Site

City

Bengbu

ZIP/Postal Code

233060

Country

China

Facility Name

Research Site

City

Changchun

ZIP/Postal Code

130021

Country

China

Facility Name

Research Site

City

Changsha

ZIP/Postal Code

410013

Country

China

Facility Name

Research Site

City

Chengdu

ZIP/Postal Code

610041

Country

China

Facility Name

Research Site

City

ChongQing

ZIP/Postal Code

400038

Country

China

Facility Name

Research Site

City

Hangzhou

ZIP/Postal Code

310003

Country

China

Facility Name

Research Site

City

Hangzhou

ZIP/Postal Code

310006

Country

China

Facility Name

Research Site

City

Hangzhou

ZIP/Postal Code

310009

Country

China

Facility Name

Research Site

City

Hefei

ZIP/Postal Code

230601

Country

China

Facility Name

Research Site

City

Nanchang

ZIP/Postal Code

330006

Country

China

Facility Name

Research Site

City

Nanjing

ZIP/Postal Code

210009

Country

China

Facility Name

Research Site

City

Nanjing

ZIP/Postal Code

210029

Country

China

Facility Name

Research Site

City

Shanghai

ZIP/Postal Code

200032

Country

China

Facility Name

Research Site

City

Shanghai

ZIP/Postal Code

200433

Country

China

Facility Name

Research Site

City

Shenyang

ZIP/Postal Code

110042

Country

China

Facility Name

Research Site

City

Wenzhou

ZIP/Postal Code

325000

Country

China

Facility Name

Research Site

City

Wuhan

ZIP/Postal Code

430022

Country

China

Facility Name

Research Site

City

Wuhan

ZIP/Postal Code

430030

Country

China

Facility Name

Research Site

City

Xi'an

ZIP/Postal Code

710038

Country

China

Facility Name

Research Site

City

Xi'an

ZIP/Postal Code

710061

Country

China

Facility Name

Research Site

City

Zhanjiang

ZIP/Postal Code

524001

Country

China

Facility Name

Research Site

City

Zhengzhou

ZIP/Postal Code

450008

Country

China

Facility Name

Research Site

City

Zhuhai

ZIP/Postal Code

519099

Country

China

Facility Name

Research Site

City

Ürümqi

ZIP/Postal Code

830000

Country

China

Facility Name

Research Site

City

Brno

ZIP/Postal Code

639 00

Country

Czechia

Facility Name

Research Site

City

Olomouc

ZIP/Postal Code

775 21

Country

Czechia

Facility Name

Research Site

City

Ostrava - Vitkovice

ZIP/Postal Code

703 84

Country

Czechia

Facility Name

Research Site

City

Praha 2

ZIP/Postal Code

128 08

Country

Czechia

Facility Name

Research Site

City

Praha 5

ZIP/Postal Code

CZ-150 18

Country

Czechia

Facility Name

Research Site

City

Praha

ZIP/Postal Code

140 59

Country

Czechia

Facility Name

Research Site

City

Avignon Cedex 09

ZIP/Postal Code

84918

Country

France

Facility Name

Research Site

City

Brest Cedex

ZIP/Postal Code

29609

Country

France

Facility Name

Research Site

City

Creteil

ZIP/Postal Code

94010

Country

France

Facility Name

Research Site

City

La Tronche

ZIP/Postal Code

38043

Country

France

Facility Name

Research Site

City

Pierre Benite Cedex

ZIP/Postal Code

69310

Country

France

Facility Name

Research Site

City

Rennes Cedex 09

ZIP/Postal Code

35033

Country

France

Facility Name

Research Site

City

Aachen

ZIP/Postal Code

52074

Country

Germany

Facility Name

Research Site

City

Berlin

ZIP/Postal Code

13125

Country

Germany

Facility Name

Research Site

City

Gauting

ZIP/Postal Code

82131

Country

Germany

Facility Name

Research Site

City

Gera

ZIP/Postal Code

07548

Country

Germany

Facility Name

Research Site

City

Hamburg

ZIP/Postal Code

20251

Country

Germany

Facility Name

Research Site

City

Heidelberg

ZIP/Postal Code

69126

Country

Germany

Facility Name

Research Site

City

Mainz

ZIP/Postal Code

55131

Country

Germany

Facility Name

Research Site

City

Regensburg

ZIP/Postal Code

93053

Country

Germany

Facility Name

Research Site

City

Budapest

ZIP/Postal Code

1083

Country

Hungary

Facility Name

Research Site

City

Budapest

ZIP/Postal Code

1106

Country

Hungary

Facility Name

Research Site

City

Budapest

ZIP/Postal Code

1121

Country

Hungary

Facility Name

Research Site

City

Budapest

ZIP/Postal Code

1134

Country

Hungary

Facility Name

Research Site

City

Deszk

ZIP/Postal Code

6772

Country

Hungary

Facility Name

Research Site

City

Gyula

ZIP/Postal Code

5700

Country

Hungary

Facility Name

Research Site

City

Kaposvár

ZIP/Postal Code

7400

Country

Hungary

Facility Name

Research Site

City

Kecskemét

ZIP/Postal Code

6000

Country

Hungary

Facility Name

Research Site

City

Miskolc

ZIP/Postal Code

3529

Country

Hungary

Facility Name

Research Site

City

Pécs

ZIP/Postal Code

7624

Country

Hungary

Facility Name

Research Site

City

Székesfehérvár

ZIP/Postal Code

8000

Country

Hungary

Facility Name

Research Site

City

Jerusalem

ZIP/Postal Code

91031

Country

Israel

Facility Name

Research Site

City

Kfar Saba

ZIP/Postal Code

95847

Country

Israel

Facility Name

Research Site

City

Petah Tikva

ZIP/Postal Code

49100

Country

Israel

Facility Name

Research Site

City

Ramat Gan

ZIP/Postal Code

5265601

Country

Israel

Facility Name

Research Site

City

Bergamo

ZIP/Postal Code

24127

Country

Italy

Facility Name

Research Site

City

Meldola

ZIP/Postal Code

47014

Country

Italy

Facility Name

Research Site

City

Milano

ZIP/Postal Code

20133

Country

Italy

Facility Name

Research Site

City

Palermo

ZIP/Postal Code

90146

Country

Italy

Facility Name

Research Site

City

Roma

ZIP/Postal Code

00100

Country

Italy

Facility Name

Research Site

City

Terni

ZIP/Postal Code

05100

Country

Italy

Facility Name

Research Site

City

Chuo-ku

ZIP/Postal Code

104-0045

Country

Japan

Facility Name

Research Site

City

Fukuoka-shi

ZIP/Postal Code

812-8582

Country

Japan

Facility Name

Research Site

City

Fukushima-shi

ZIP/Postal Code

960-1295

Country

Japan

Facility Name

Research Site

City

Himeji-shi

ZIP/Postal Code

670-8520

Country

Japan

Facility Name

Research Site

City

Iwakuni-shi

ZIP/Postal Code

740-8510

Country

Japan

Facility Name

Research Site

City

Kashiwa

ZIP/Postal Code

227-8577

Country

Japan

Facility Name

Research Site

City

Koto-ku

ZIP/Postal Code

135-8550

Country

Japan

Facility Name

Research Site

City

Kurume-shi

ZIP/Postal Code

830-0011

Country

Japan

Facility Name

Research Site

City

Kyoto

ZIP/Postal Code

606-8507

Country

Japan

Facility Name

Research Site

City

Matsuyama-shi

ZIP/Postal Code

791-0280

Country

Japan

Facility Name

Research Site

City

Nagoya-shi

ZIP/Postal Code

464-8681

Country

Japan

Facility Name

Research Site

City

Nagoya-shi

ZIP/Postal Code

466-8560

Country

Japan

Facility Name

Research Site

City

Okayama-shi

ZIP/Postal Code

700-8558

Country

Japan

Facility Name

Research Site

City

Osakasayama

ZIP/Postal Code

589-8511

Country

Japan

Facility Name

Research Site

City

Sakai-shi

ZIP/Postal Code

591-8555

Country

Japan

Facility Name

Research Site

City

Tokushima-shi

ZIP/Postal Code

770-8503

Country

Japan

Facility Name

Research Site

City

Ube-shi

ZIP/Postal Code

755-0241

Country

Japan

Facility Name

Research Site

City

Yokohama-shi

ZIP/Postal Code

236-0004

Country

Japan

Facility Name

Research Site

City

Yokohama-shi

ZIP/Postal Code

241-8515

Country

Japan

Facility Name

Research Site

City

Changwon

ZIP/Postal Code

51353

Country

Korea, Republic of

Facility Name

Research Site

City

Cheongju-si

ZIP/Postal Code

28644

Country

Korea, Republic of

Facility Name

Research Site

City

Daegu

ZIP/Postal Code

42415

Country

Korea, Republic of

Facility Name

Research Site

City

Incheon

ZIP/Postal Code

21565

Country

Korea, Republic of

Facility Name

Research Site

City

Jinju-si

ZIP/Postal Code

660-702

Country

Korea, Republic of

Facility Name

Research Site

City

Seongnam-si

ZIP/Postal Code

13620

Country

Korea, Republic of

Facility Name

Research Site

City

Seongnam-Si

ZIP/Postal Code

463-712

Country

Korea, Republic of

Facility Name

Research Site

City

Seoul

ZIP/Postal Code

05505

Country

Korea, Republic of

Facility Name

Research Site

City

Seoul

ZIP/Postal Code

110746

Country

Korea, Republic of

Facility Name

Research Site

City

Amsterdam

ZIP/Postal Code

1066 CX

Country

Netherlands

Facility Name

Research Site

City

Arnhem

ZIP/Postal Code

6815 AD

Country

Netherlands

Facility Name

Research Site

City

Groningen

ZIP/Postal Code

9713 GZ

Country

Netherlands

Facility Name

Research Site

City

Hengelo

ZIP/Postal Code

7555 DL

Country

Netherlands

Facility Name

Research Site

City

Maastricht

ZIP/Postal Code

6202 AZ

Country

Netherlands

Facility Name

Research Site

City

Rotterdam

ZIP/Postal Code

3015 GD

Country

Netherlands

Facility Name

Research Site

City

Bialystok

ZIP/Postal Code

15-027

Country

Poland

Facility Name

Research Site

City

Białystok

ZIP/Postal Code

15-540

Country

Poland

Facility Name

Research Site

City

Lublin

ZIP/Postal Code

20-954

Country

Poland

Facility Name

Research Site

City

Olsztyn

ZIP/Postal Code

10-357

Country

Poland

Facility Name

Research Site

City

Warszawa

ZIP/Postal Code

02-781

Country

Poland

Facility Name

Research Site

City

Cluj Napoca

ZIP/Postal Code

400015

Country

Romania

Facility Name

Research Site

City

Floresti

ZIP/Postal Code

407280

Country

Romania

Facility Name

Research Site

City

Suceava

ZIP/Postal Code

720237

Country

Romania

Facility Name

Research Site

City

Moscow

ZIP/Postal Code

105229

Country

Russian Federation

Facility Name

Research Site

City

Omsk

ZIP/Postal Code

644013

Country

Russian Federation

Facility Name

Research Site

City

Rostov-on-Don

ZIP/Postal Code

344037

Country

Russian Federation

Facility Name

Research Site

City

Saint Petersburg

ZIP/Postal Code

195271

Country

Russian Federation

Facility Name

Research Site

City

Saint-Petersburg

ZIP/Postal Code

194291

Country

Russian Federation

Facility Name

Research Site

City

Sankt-Peterburg

ZIP/Postal Code

196603

Country

Russian Federation

Facility Name

Research Site

City

St. Petersburg

ZIP/Postal Code

197758

Country

Russian Federation

Facility Name

Research Site

City

Ufa

ZIP/Postal Code

450054

Country

Russian Federation

Facility Name

Research Site

City

Banska Bystrica

ZIP/Postal Code

97517

Country

Slovakia

Facility Name

Research Site

City

Bardejov

ZIP/Postal Code

085 01

Country

Slovakia

Facility Name

Research Site

City

Bratislava

ZIP/Postal Code

82606

Country

Slovakia

Facility Name

Research Site

City

Bratislava

ZIP/Postal Code

833 01

Country

Slovakia

Facility Name

Research Site

City

Kosice

ZIP/Postal Code

041 91

Country

Slovakia

Facility Name

Research Site

City

Nove Zamky

ZIP/Postal Code

940 01

Country

Slovakia

Facility Name

Research Site

City

Trnava

ZIP/Postal Code

91708

Country

Slovakia

Facility Name

Research Site

City

A Coruña

ZIP/Postal Code

15006

Country

Spain

Facility Name

Research Site

City

Badajoz

ZIP/Postal Code

06008

Country

Spain

Facility Name

Research Site

City

Badalona

ZIP/Postal Code

08916

Country

Spain

Facility Name

Research Site

City

Barcelona

ZIP/Postal Code

08041

Country

Spain

Facility Name

Research Site

City

Madrid

ZIP/Postal Code

08035

Country

Spain

Facility Name

Research Site

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Research Site

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

Research Site

City

Santander

ZIP/Postal Code

39008

Country

Spain

Facility Name

Research Site

City

Valencia

ZIP/Postal Code

46010

Country

Spain

Facility Name

Research Site

City

Zaragoza

ZIP/Postal Code

50009

Country

Spain

Facility Name

Research Site

City

Changhua

ZIP/Postal Code

50006

Country

Taiwan

Facility Name

Research Site

City

Kaohsiung City

ZIP/Postal Code

83301

Country

Taiwan

Facility Name

Research Site

City

Kaohsiung

ZIP/Postal Code

82445

Country

Taiwan

Facility Name

Research Site

City

Taichung

ZIP/Postal Code

40447

Country

Taiwan

Facility Name

Research Site

City

Taichung

ZIP/Postal Code

40705

Country

Taiwan

Facility Name

Research Site

City

Tainan

ZIP/Postal Code

704

Country

Taiwan

Facility Name

Research Site

City

Tainan

ZIP/Postal Code

736

Country

Taiwan

Facility Name

Research Site

City

Taipei

ZIP/Postal Code

11217

Country

Taiwan

Facility Name

Research Site

City

Taipei

ZIP/Postal Code

235

Country

Taiwan

Facility Name

Research Site

City

Ankara

ZIP/Postal Code

06230

Country

Turkey

Facility Name

Research Site

City

Ankara

Country

Turkey

Facility Name

Research Site

City

Edirne

ZIP/Postal Code

22030

Country

Turkey

Facility Name

Research Site

City

Istanbul

ZIP/Postal Code

34030

Country

Turkey

Facility Name

Research Site

City

Izmir

ZIP/Postal Code

35100

Country

Turkey

Facility Name

Research Site

City

Izmir

ZIP/Postal Code

35620

Country

Turkey

Facility Name

Research Site

City

Dnipro

ZIP/Postal Code

49102

Country

Ukraine

Facility Name

Research Site

City

Ivano-Frankivsk

ZIP/Postal Code

76018

Country

Ukraine

Facility Name

Research Site

City

Kirovohrad

ZIP/Postal Code

25006

Country

Ukraine

Facility Name

Research Site

City

Kryvyi Rih

ZIP/Postal Code

50048

Country

Ukraine

Facility Name

Research Site

City

Kyiv

ZIP/Postal Code

03022

Country

Ukraine

Facility Name

Research Site

City

Kyiv

ZIP/Postal Code

03115

Country

Ukraine

Facility Name

Research Site

City

Lviv

ZIP/Postal Code

79031

Country

Ukraine

Facility Name

Research Site

City

Odesa

ZIP/Postal Code

65055

Country

Ukraine

Facility Name

Research Site

City

Sumy

ZIP/Postal Code

40022

Country

Ukraine

Facility Name

Research Site

City

Vinnytsia

ZIP/Postal Code

21029

Country

Ukraine

Facility Name

Research Site

City

Zaporizhzhia

ZIP/Postal Code

69040

Country

Ukraine

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing URL

https://astrazenecagroup-dt.pharmacm.com/DT/Home

Citations:

PubMed Identifier

33285097

Citation

Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. doi: 10.1016/S1470-2045(20)30539-8. Epub 2020 Dec 4.

Results Reference

derived

PubMed Identifier

31590988

Citation

Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6. Epub 2019 Oct 4.

Results Reference

derived

Links:

URL

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D419QC00001&attachmentIdentifier=042de696-9399-4abc-8643-673f1237463a&fileName=d419qc00001-csp-v5_Redacted.pdf&versionIdentifier=

Description

Redacted CSP

URL

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D419QC00001&attachmentIdentifier=dafb894c-0f08-4319-a2fe-7389ae3ba87f&fileName=D419qc00001_SAP_Redacted.pdf&versionIdentifier=

Description

Redacted SAP

URL

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D419QC00001&attachmentIdentifier=11d0f58c-9d10-4c9a-95c3-000528295c1c&fileName=d419qc00001-csp-v5_Redacted.pdf&versionIdentifier=

Description

CSPv5_redacted

Learn more about this trial

Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN)

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Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN) (CASPIAN)

Small Cell Lung Carcinoma Extensive Disease

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial