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

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)

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.

Study Overview

• Status: Completed
• Conditions: Extensive-stage Small Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Etoposide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Panagyurishte, Bulgaria, 4500
    • Research Site
  • Ruse, Bulgaria, 7002
    • Research Site
  • Sofia, Bulgaria, 1407
    • Research Site
  • Sofia, Bulgaria, 1330
    • Research Site
  • Sofia, Bulgaria, 1303
    • Research Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Research Site
• Czechia
  • Burgas, Czechia, 180 81
    • Research Site
  • Olomouc, Czechia, 779 00
    • Research Site
  • Ostrava, Czechia, 703 00
    • Research Site
• Germany
  • Berlin, Germany, 13125
    • Research Site
  • Berlin, Germany, 12351
    • Research Site
  • Gauting, Germany, 82131
    • Research Site
  • Hamburg, Germany, 20251
    • Research Site
  • Jena, Germany, 07747
    • Research Site
  • Kassel, Germany, 34125
    • Research Site
  • Köln, Germany, 51109
    • Research Site
• Italy
  • Ancona, Italy, 60126
    • Research Site
  • Bari, Italy, 70124
    • Research Site
  • Milano, Italy, 20141
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Orbassano, Italy, 10043
    • Research Site
  • Palermo, Italy, 90146
    • Research Site
  • Roma, Italy, 00168
    • Research Site
• Turkey
  • Adapazari, Turkey, 54290
    • Research Site
  • Ankara, Turkey, 06800
    • Research Site
  • Ankara, Turkey, 06100
    • Research Site
  • Ankara, Turkey, 06010
    • Research Site
  • Antalya, Turkey, 07070
    • Research Site
  • Bursa, Turkey, 16059
    • Research Site
  • Edirne, Turkey, 22030
    • Research Site
  • Istanbul, Turkey, 34098
    • Research Site
  • Istanbul, Turkey, 34722
    • Research Site
  • Izmir, Turkey, 35100
    • Research Site
  • Malatya, Turkey, 44280
    • Research Site
  • Pamukkale, Turkey, 20070
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Durvalumab - (cisplatin or carboplatin) - Etoposide; 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; Participants will receive durvalumab via IV infusion on Day 1 of each cycle.; Drug: Cisplatin; Participants will receive cisplatin via IV administration on Day 1 of each cycle.; Drug: Carboplatin; Participants will receive carboplatin via IV administration Day 1 of each cycle.; Drug: Etoposide; Participants will receive etoposide via IV administration on days 1 to 3 of each cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Incidence of Grade 3 or Higher Adverse Events (AEs)	Incidence of Grade 3 or higher adverse events to evaluate safety and tolerability profile of durvalumab + Platinum (cisplatin or carboplatin) plus etoposide (EP) treatment was assessed.	From first dose of study treatment until 90 days after treatment discontinuation, up to 2.5 years.
Number of Participants With Incidence of Immune Mediated Adverse Events (imAEs)	Immune mediated adverse events (imAEs) were assessed to evaluate safety and tolerability profile of durvalumab + EP treatment. An imAE is defined as an AESI that is associated with drug exposure and is consistent with an immune-mediated mechanism of action (MOA) and where there is no clear alternate etiology.	From first dose of study treatment until 90 days after treatment discontinuation, up to 2.5 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Efficacy of durvalumab + EP treatment by evaluating PFS according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) was assessed. 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 withdrew from Investigational medicinal product (IMP) or received another anticancer therapy prior to progression.	From first dose of study treatment until disease progression or death, up to 2.5 years.
Percentage of Participants Alive and Progression-free at 12 Months From First Date of Treatment (PFS12)	The efficacy of durvalumab + EP treatment by evaluating PFS12 according to RECIST 1.1 was assessed.	From first date of study treatment until 12 months.
Objective Response Rate (ORR)	The efficacy of durvalumab + EP treatment by evaluating ORR according to RECIST 1.1 was assessed. 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 or the last evaluable assessment in the absence of progression, up to 2.5 years.
Duration of Response (DoR)	The efficacy of durvalumab + EP treatment by evaluating DoR according to RECIST 1.1 was assessed. 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 the date of first documented response until the first date of documented progression or death in the absence of disease progression, up to 2.5 years.
Percentage of Participants Remaining in Response, 12 Months After First Documented Objective Response (DoR12)	The efficacy of durvalumab + EP treatment by evaluating DoR12 according to RECIST 1.1 was assessed.	From the date of first documented response until the first date of documented progression or death in the absence of disease progression, up to 2.5 years.
Overall Survival (OS)	Assessment of the efficacy of durvalumab + EP treatment by evaluating OS. The OS is the time from the first date of treatment until death due to any cause.	From first dose of study treatment to death, up to 2.5 years.
Percentage of Participants Alive at 12 Months From First Date of Treatment (OS12)	The efficacy of durvalumab + EP treatment by evaluating OS12 was assessed.	From first dose of study treatment till 12 months.
Number of Participants With Adverse Events and Serious Adverse Events	To evaluate safety and tolerability profile of durvalumab + EP treatment, adverse events and serious adverse events were assessed.	From first dose of study treatment until 90 days after discontinuation, up to 2.5 years.
Number of Participants With Adverse Events of Special Interests	To evaluate safety and tolerability profile of durvalumab + EP treatment, adverse events of special interests were assessed. An AESI is an AE of scientific and medical interest specific to understanding of the IMP. AESIs for durvalumab include, but are not limited to, events with a potential inflammatory or immune-mediated mechanism and which may require more frequent monitoring and/or interventions such as steroids, immunosuppressants, and/or hormone replacement therapy. This includes adverse events of special/ possible interest.	From first dose of study treatment until 90 days after discontinuation, up to 2.5 years.

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Redacted CSP
• Redacted CSR Synopsis
• Redacted SAP

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Actual): June 12, 2023
• Study Completion (Actual): January 2, 2025

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): May 23, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Chemotherapy; Platinum-based chemotherapy; Aggressive malignancy; Programmed cell death ligand-1
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Durvalumab; Etoposide; Carboplatin
• Other Study ID Numbers: D419QC00007; 2020-005537-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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 requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

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 Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No