Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy
- Conditions
- Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03703297
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients with LS-SCLC Who Have Not Progressed Following Concurrent Chemoradiation Therapy
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 730
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Placebo Placebo Placebo: Placebo saline solution (IV) q4w in combination with a second placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by a single placebo saline solution q4w. The first placebo saline solution monotherapy dose q4w will be 4 weeks after the final dose of the 2 placebo saline solutions in combination. Durvalumab + Placebo Placebo Durvalumab monotherapy: Durvalumab (1500 mg intravenous \[IV\]) q4w in combination with placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with placebo saline solution. Durvalumab + Placebo Durvalumab Durvalumab monotherapy: Durvalumab (1500 mg intravenous \[IV\]) q4w in combination with placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with placebo saline solution. Durvalumab + Tremelimumab Durvalumab Durvalumab in combination with tremelimumab: Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with tremelimumab. Durvalumab + Tremelimumab Tremelimumab Durvalumab in combination with tremelimumab: Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with tremelimumab.
- Primary Outcome Measures
Name Time Method Durvalumab Versus Placebo: Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 Response evaluations performed every 8 weeks (q8w) ± 1 week up to 72 weeks, then every 12 weeks (q12w) ± 1 week up to 96 weeks, and then every 24 weeks (q24w) thereafter until PD, up to DCO date 15 January 2024 (a maximum of approximately 1936 days) PFS per RECIST 1.1 assessed by BICR was defined as the time from the date of randomization until the date of objective disease progression (PD) or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anticancer therapy prior to progression. 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) - this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm) from nadir. Median PFS was calculated using Kaplan-Meier method and its confidence interval (CI) using Brookmeyer-Crowley method.
Durvalumab Versus Placebo: Overall Survival (OS) From date of randomization until death due to any cause, up to DCO date 15 January 2024 (a maximum of approximately 1936 days) OS was defined as the time from the date of randomization until death due to any cause. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
- Secondary Outcome Measures
Name Time Method Durvalumab Plus Tremelimumab Combination Versus Placebo: Progression-Free Survival Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1 Response evaluations performed q8w ± 1 week up to 72 weeks, then q12w ± 1 week up to 96 weeks, and then q24w thereafter until PD, up to approximately 89 months PFS per RECIST 1.1 assessed by BICR is defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to progression. PD is defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir.
Durvalumab Plus Tremelimumab Combination Versus Placebo: Overall Survival From date of randomization until death due to any cause, up to approximately 89 months OS is defined as the time from the date of randomization until death due to any cause.
Durvalumab Versus Placebo: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1 Response evaluations performed q8w ± 1 week up to 72 weeks, then q12w ± 1 week up to 96 weeks, and then q24w thereafter until PD, up to DCO date 15 January 2024 (a maximum of approximately 1936 days) ORR per RECIST 1.1 assessed by BICR was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) (i.e., unconfirmed response). 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. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Durvalumab Plus Tremelimumab Combination Versus Placebo: Objective Response Rate Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1 From date of randomization until death due to any cause, up to approximately 89 months ORR per RECIST 1.1 assessed by BICR is defined as the percentage of participants with at least 1 visit response of CR or PR (i.e., unconfirmed response). CR is 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. PR is defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Durvalumab Plus Tremelimumab Combination Versus Placebo: Time to Death or Distant Metastasis (TTDM) Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1 Response evaluations performed q8w ± 1 week up to 72 weeks, then q12w ± 1 week up to 96 weeks, and then q24w thereafter until PD, up to approximately 89 months TTDM per RECIST 1.1 is defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the radiation field according to RECIST 1.1 or proven by biopsy.
Durvalumab Versus Placebo: Percentage of Participants Progression-Free at 18 Months Following Randomization (PFS18) Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1 Month 18 PFS per RECIST 1.1 assessed by BICR was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anticancer therapy prior to progression. 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) - this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir. The PFS18 was defined as the Kaplan-Meier estimate of PFS per RECIST 1.1 as assessed by BICR at 18 months following randomization.
Durvalumab Plus Tremelimumab Combination Versus Placebo: Percentage of Participants Progression-Free at 18 Months Following Randomization Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1 Month 18 PFS per RECIST 1.1 assessed by BICR is defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to progression. PD is defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir. The PFS18 is defined as the Kaplan-Meier estimate of PFS per RECIST 1.1 as assessed by BICR at 18 months following randomization.
Durvalumab Versus Placebo: Percentage of Participants Progression-Free at 24 Months Following Randomization (PFS24) Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1 Month 24 PFS per RECIST 1.1 assessed by BICR was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anticancer therapy prior to progression. 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) - this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir. The PFS24 was defined as the Kaplan-Meier estimate of PFS per RECIST 1.1 as assessed by BICR at 24 months following randomization.
Durvalumab Plus Tremelimumab Combination Versus Placebo: Percentage of Participants Progression-Free at 24 Months Following Randomization Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1 Month 24 PFS per RECIST 1.1 assessed by BICR is defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to progression. PD is defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this included the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir. The PFS24 is defined as the Kaplan-Meier estimate of PFS per RECIST 1.1 as assessed by BICR at 24 months following randomization.
Durvalumab Versus Placebo: Percentage of Participants Alive at 24 Months From Randomization (OS24) Month 24 OS was defined as the time from the date of randomization until death due to any cause. The OS24 was defined as the Kaplan-Meier estimate of OS at 24 months after randomization.
Durvalumab Plus Tremelimumab Combination Versus Placebo: Percentage of Participants Alive at 24 Months From Randomization Month 24 OS is defined as the time from the date of randomization until death due to any cause. The OS24 is defined as the Kaplan-Meier estimate of OS at 24 months after randomization.
Durvalumab Versus Placebo: Percentage of Participants Alive at 36 Months From Randomization (OS36) Month 36 OS was defined as the time from the date of randomization until death due to any cause. The OS36 was defined as the Kaplan-Meier estimate of OS at 36 months after randomization.
Durvalumab Plus Tremelimumab Combination Versus Placebo: Percentage of Participants Alive at 36 Months From Randomization Month 36 OS is defined as the time from the date of randomization until death due to any cause. The OS36 is defined as the Kaplan-Meier estimate of OS at 36 months after randomization.
Durvalumab Plus Tremelimumab Combination Versus Placebo: Time From Randomization to Second Progression (PFS2) Response evaluations performed q8w ± 1 week up to 72 weeks, then q12w ± 1 week up to 96 weeks, and then q24w thereafter until PD, up to approximately 89 months PFS2 is defined as the time from the date of randomization to the earliest of the progression event subsequent to the first subsequent anticancer therapy (excluding radiotherapy) or death. The date of second progression is recorded by the Investigator in the eCRF at each assessment and defined according to local standard clinical practice and might involve any of the following: objective radiological imaging, symptomatic progression, or death.
Durvalumab Versus Durvalumab Plus Tremelimumab: Progression-Free Survival Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1 Response evaluations performed q8w ± 1 week up to 72 weeks, then q12w ± 1 week up to 96 weeks, and then q24w thereafter until PD, up to approximately 89 months PFS per RECIST 1.1 assessed by BICR is defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to progression. PD is defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir.
Durvalumab Versus Durvalumab Plus Tremelimumab: Objective Response Rate Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1 From date of randomization until death due to any cause, up to approximately 89 months ORR per RECIST 1.1 assessed by BICR is defined as the percentage of participants with at least 1 visit response of CR or PR (i.e., unconfirmed response). CR is 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. PR is defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Durvalumab Versus Durvalumab Plus Tremelimumab: Overall Survival From date of randomization until death due to any cause, up to approximately 89 months OS is defined as the time from the date of randomization until death due to any cause.
Durvalumab Plus Tremelimumab Versus Placebo: Change From Baseline in Patient-Reported Symptoms as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) Baseline (Day 1) and up to approximately 89 months Patient-reported outcomes for 5 disease related symptoms will be assessed using EORTC QLQ-Core 30 (C30) items questionnaire (fatigue, appetite loss) and EORTC QLQ-Lung Cancer module 13 (LC13) (dyspnea, cough and pain in chest). An outcome variable consisting of a score from 0 to 100 will be derived for each of the symptom scales/symptom items, functional scales, and global health status (GHS) scale with higher scores on GHS/QoL and functioning scales representing better health status/function, but higher scores on symptom scales/items representing greater symptom severity.
Durvalumab: Serum Concentration of Durvalumab End of infusion on Cycle 1 Day 1, pre-infusion on Cycle 2 (Week 4), Cycle 5 (Week 16) and Cycle 26 (Week 100) and Month 3 post last dose of study treatment (Week 119) (each treatment cycle is 28 days) Blood samples were collected to determine the concentration of durvalumab.
Durvalumab Plus Tremelimumab: Serum Concentration of Tremelimumab Up to approximately 27 months Blood samples will be collected to determine the concentration of tremelimumab.
Durvalumab: Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab From first dose of study drug (Day 1) up to DCO date 15 January 2024 (a maximum of approximately 1936 days) Blood samples were collected to determine the presence of ADAs for durvalumab using validated assays. Treatment-emergent ADA-positive was defined as either treatment-induced (post-baseline ADA-positive only) or treatment-boosted ADA (baseline positive ADA titer that was boosted to ≥4 fold during the study period). Treatment-induced ADA was defined as ADA positive post-baseline and not detected at baseline. Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher level (greater than the analytical variance of the assay) following drug administration. Number of participants with treatment-emergent ADA (ADA incidence) are presented.
Durvalumab Plus Tremelimumab: Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab Up to approximately 30 months Blood samples will be collected to determine the presence of ADAs for tremelimumab using validated assays. Treatment-emergent ADA-positive is defined as either treatment-induced (post-baseline ADA-positive only) or treatment-boosted ADA (baseline positive ADA titer that was boosted to ≥4 fold during the study period). Treatment-boosted ADA is defined as a baseline positive ADA titer that was boosted to a 4-fold or higher level (greater than the analytical variance of the assay) following drug administration. Treatment-induced ADA is defined as ADA positive post-baseline and not detected at baseline.
Durvalumab Versus Durvalumab Plus Tremelimumab: Number of Participants With Positive Programmed Death Ligand 1 (PD-L1) Status Based on Progression-Free Survival, Overall Survival, and Objective Response Rate Up to approximately 89 months Blood samples will be collected for clinical biomarker testing and a tumor specimen will be collected as per tumor specimen collection requirements. The specimen will be evaluated by immunohistochemistry to determine the expression of tumor specific antigens and immune markers. The PD-L1 is a biomarker and will be assessed using the VENTANA PD-L1 (SP263) assay.
Trial Locations
- Locations (1)
Research Site
🇻🇳Ho Chi Minh City, Vietnam
Research Site🇻🇳Ho Chi Minh City, Vietnam