Study of Durvalumab in Combination With Platinum and Etoposide for the First Line Treatment of Patients With Extensive-stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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Study to determine the safety and tolerability profile of durvalumab with platinum (cisplatin or carboplatin) plus etoposide (EP) as first-line treatment in participants with extensive-stage small-cell lung cancer.

Detailed Description
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The study will be conducted in North America, Europe and Turkey. In this single arm study participants will be treated with with durvalumab alone and concurrently with platinum-based chemotherapy and etoposide during the study period until radiological disease progression, unless there is clinical progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met, as per investigator assessment.

Official Title
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A Phase IIIb, Single-arm, Multi-center, International Study of Durvalumab in Combination With Platinum and Etoposide for the First Line Treatment of Patients With Extensive-stage Small Cell Lung Cancer (LUMINANCE)

Conditions
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Extensive-stage Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: Etoposide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically- or cytologically-documented ES-SCLC (stage IV [T any, N any, M1 a/b], or with 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 (Brain metastases; must be asymptomatic or treated and stable off steroids and anticonvulsants for at least 1 month prior to study treatment) Participants must be considered suitable to receive a platinum-based chemotherapy regimen as 1st line treatment for the ES-SCLC. Chemotherapy must contain either cisplatin or carboplatin in combination with etoposide World Health Organization/ Eastern Cooperative Oncology Group performance status of 0 to 2 at enrollment Baseline computed tomography/ magnetic resonance imaging results of the brain, chest and abdomen (including liver and adrenal glands) within 28 days prior to the treatment initiation No prior exposure to immune-mediated therapy including, but not limited to, other anti- CTLA-4, anti-Programmed cell death-1 (PD-1), anti- Programmed cell death ligand-1 (PD-L1), and anti-PD-L2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines Adequate organ and marrow function Body weight > 30 kg Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal participants Exclusion Criteria: History of allogeneic organ transplantation Active or prior documented autoimmune or inflammatory disorders, systemic lupus erythematosus, sarcoidosis syndrome, or wegener syndrome Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of Investigational medicinal product (IMP) and of low potential risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease History of leptomeningeal carcinomatosis and active primary immunodeficiency Active infection including tuberculosis, hepatitis B, hepatitis C, human immunodeficiency virus Any unresolved toxicity Common Terminology Criteria for Adverse Events Grade ≥ 2 from previous anticancer therapy Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients Received prior systemic therapy for ES-SCLC Medical contraindication to platinum (cisplatin or carboplatin)-etoposide-based chemotherapy Any concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable Planned consolidation chest radiation therapy. Radiation therapy outside of the chest for palliative care is allowed but must be completed before first dose of the study medication Receipt of live attenuated vaccine within 30 days prior to the first dose of in IMP Major surgical procedure within 28 days prior to the first dose of IMP Participants who have received prior immunotherapy agents including anti-PD-1 or anti PD-L1 Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab Participation in another clinical study with an investigational product administered in the last 4 weeks Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab and 180 days after the last dose of etoposide

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Durvalumab - (cisplatin or carboplatin) - Etoposide<br>Participants will receive durvalumab dose A administered via intravenous (IV) infusion concurrently with platinum-based chemotherapy and etoposide every 3 weeks (q3w). Thereafter, durvalumab monotherapy will be continued every 4 weeks post-chemotherapy unless specific treatment discontinuation criteria are met. | Drug: Durvalumab<br>* Participants will receive durvalumab via IV infusion on Day 1 of each cycle.<br>Drug: Cisplatin<br>* Participants will receive cisplatin via IV administration on Day 1 of each cycle.<br>Drug: Carboplatin<br>* Participants will receive carboplatin via IV administration Day 1 of each cycle.<br>Drug: Etoposide<br>* Participants will receive etoposide via IV administration on days 1 to 3 of each cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with incidence of Grade 3 and higher adverse events (AEs) | Assessment of incidence of Grade 3 and higher adverse events to evaluate safety and tolerability profile of durvalumab + EP treatment. | Until disease progression (Approximately upto 1.6 Years) | 
| Number of participants with incidence of Immune mediated adverse events (imAEs) | Assessment of imAEs to evaluate safety and tolerability profile of durvalumab + EP treatment. | Until disease progression (Approximately upto 1.6 Years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Assessment of efficacy of durvalumab + EP treatment by evaluating PFS according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The PFS is the time from the first date of treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraws from Investigational medicinal product (IMP) or receives another anticancer therapy prior to progression. | From screening until disease progression (Approximately 2 Years) | 
| Objective response rate (ORR) | Assessment of the efficacy of durvalumab + EP treatment by evaluating ORR according to RECIST 1.1. The ORR will be assessed based on Investigator-assessed response to treatment of complete response (CR) and partial response (PR), per RECIST1.1. | From screening until disease progression (Approximately 2 Years) | 
| Duration of response (DoR) | Assessment of the efficacy of durvalumab + EP treatment by evaluating DoR according to RECIST 1.1. The DoR is time from the date of first documented response per RECIST1.1 until the first date of documented progression per RECIST1.1 or death in the absence of disease progression. | From screening until disease progression (Approximately 2 Years) | 
| Percentage of participants remaining in response, 12 months from the time of first documented objective response (DoR12) | Assessment of the efficacy of durvalumab + EP treatment by evaluating DoR12 according to RECIST 1.1. | From screening until disease progression (Approximately 2 Years) | 
| Percentage of participants alive and progression-free at 12 months from first date of treatment (PFS12) | Assessment of the efficacy of durvalumab + EP treatment by evaluating PFS12 according to RECIST 1.1. | From screening until disease progression (Approximately 2 Years) | 
| Overall (OS) | Assessment of the efficacy of durvalumab + EP treatment by evaluating OS according to RECIST 1.1. The OS is the time from the first date of treatment until death due to any cause. | From screening until death due to any cause (Approximately 2 Years) | 
| Percentage of participants alive at 12 months from first date of treatment (OS12) | Assessment of the efficacy of durvalumab + EP treatment by evaluating OS12 according to RECIST 1.1. | From screening until disease progression (Approximately 2 Years) | 
| Number of participants with adverse events and serious adverse events | Assessment of adverse events and serious adverse events to evaluate safety and tolerability profile of durvalumab + EP treatment. | From Cycle 1 (3 weeks [21 days]) until disease progression (Approximately 2 Years) | 
| Number of participants with adverse events of special interests | Assessment of adverse events of special interests to evaluate safety and tolerability profile of durvalumab + EP treatment. | From Cycle 1 (3 weeks [21 days]) until disease progression (Approximately 2 Years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy, Aggressive malignancy, Programmed cell death ligand-1, Platinum-based chemotherapy