Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy

Study Overview
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Brief Summary
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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

Official Title
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A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients With Limited Stage Small Cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC)

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Tremelimumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically or cytologically documented limited-stage small cell lung cancer (stage I-III). Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to randomization and the first dose of IP. Chemotherapy must contain platinum and IV etoposide. Radiotherapy must be either total 60-66 Gy over 6 weeks for the standard QD regimen or total 45 Gy over 3 weeks for hyperfractionated BD schedules. PCI may be delivered at the discretion of investigator and local standard of care, and must be conducted after the end of cCRT and completed between 1 to 42 days to first dose of IP. 4 .Have not progressed following definitive concurrent chemoradiation 5 .Life expectancy ≥ 12 weeks at Day 1. 6. ECOG 0 or 1 at enrolment. Exclusion criteria: Extensive-stage SCLC Active or prior documented autoimmune or inflammatory disorders Uncontrolled intercurrent illness, including but not limited to interstitial lung disease. Active infection including tuberculosis, HIV, hepatitis B and C Patients who received sequential chemotherapy and radiotherapy (no overlap of RT with chemotherapy)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Durvalumab + Placebo<br>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. | Drug: Durvalumab<br>* Durvalumab IV (intravenous infusion)<br>* Other names: MEDI4736;Other: Placebo<br>* Placebo IV (intravenous infusion)<br>|
| Experimental: Durvalumab + Tremelimumab<br>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. | Drug: Durvalumab<br>* Durvalumab IV (intravenous infusion)<br>* Other names: MEDI4736;Drug: Tremelimumab<br>* Tremelimumab IV (intravenous infusion)<br>|
| Placebo Comparator: Placebo + Placebo<br>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. | Other: Placebo<br>* Placebo IV (intravenous infusion)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of PFS | Approximately 6 years | 
| Overall Survival (OS) | To assess the efficacy of Durvalumab monotherapy vs Placebo in terms of OS | Approximately 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | To assess the efficacy of Durvalumab & Tremelimumab combination therapy vs Placebo in terms of OS | Approximately 6 years | 
| Objective Response Rate (ORR) |  | Approximately 6 years | 
| Progression-free survival PFS | To assess the efficacy of durvalumab and tremelimumab combination therapy compared to placebo in terms of PFS | Approximately 6 years | 
| Progression-free survival at 18 months (PFS18) |  | Approximately 6 years | 
| Progression-free survival at 24 months (PFS24) |  | Approximately 6 years | 
| Time to death or distant metastasis (TTDM) |  | Approximately 6 years | 
| Proportion of patients alive at 24 months (OS24) |  | Approximately 6 years | 
| Proportion of patients alive at and 36 months (OS36) |  | Approximately 6 years | 
| Time from randomization to second progression (PFS2) |  | Approximately 6 years | 
| To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-C30 v3 |  | Approximately 6 years | 
| To assess the PK of durvalumab and tremelimumab in blood (peak trough concentration) |  | Approximately 6 years | 
| Presence of anti-drug antibodies (ADA) for durvalumab and tremelimumab (confirmatory results: positive or negative) |  | Approximately 6 years | 
| PD-L1 expression in tumor and/or immune cells relative to response/efficacy outcomes (PFS, OS & ORR). | To investigate the relationship between PDL1 expression & spatial distribution with Durva (mono) therapy & Durva+Treme (combination) therapy | Approximately 6 years | 
| To assess symptoms and health-related QoL in patients treated withdurvalumab or durvalumab and tremelimumab combination therapy compared to placebo using the EORTC QLQ-LC13 |  | Approximately 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Small Cell Lung Cancer, SCLC, LS-SCLC, Limited Stage, Carcinoma, Lung Cancer