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

NCT04774380 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: D419QC000072020-005537-32
• Study Type: interventional
• Target: 152
• Locations: 6 countries
• Sites: 35

Brief Summary

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.

Conditions

Extensive-stage Small Cell Lung Cancer

Keywords

Chemotherapy; Aggressive malignancy; Programmed cell death ligand-1; Platinum-based chemotherapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Progression-free Survival (PFS)

  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)

  From first date of study treatment until 12 months.

• Objective Response Rate (ORR)

  From screening until disease progression or the last evaluable assessment in the absence of progression, up to 2.5 years.

• Duration of Response (DoR)

  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)

  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.

Study Arms (1)

Durvalumab - (cisplatin or carboplatin) - Etoposide

EXPERIMENTAL

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; Drug: Cisplatin; Drug: Carboplatin; Drug: Etoposide

Interventions

Durvalumab DRUG

Participants will receive durvalumab via IV infusion on Day 1 of each cycle.

Durvalumab - (cisplatin or carboplatin) - Etoposide

Cisplatin DRUG

Participants will receive cisplatin via IV administration on Day 1 of each cycle.

Durvalumab - (cisplatin or carboplatin) - Etoposide

Carboplatin DRUG

Participants will receive carboplatin via IV administration Day 1 of each cycle.

Durvalumab - (cisplatin or carboplatin) - Etoposide

Etoposide DRUG

Participants will receive etoposide via IV administration on days 1 to 3 of each cycle.

Durvalumab - (cisplatin or carboplatin) - Etoposide

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (35)

Research Site

Panagyurishte, 4500, Bulgaria

Location

Research Site

Rousse, 7002, Bulgaria

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Sofia, 1303, Bulgaria

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Sofia, 1330, Bulgaria

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Sofia, 1407, Bulgaria

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Montreal, Quebec, H4A 3J1, Canada

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Burgas, 180 81, Czechia

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Olomouc, 779 00, Czechia

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Ostrava, 703 00, Czechia

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Berlin, 12351, Germany

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Berlin, 13125, Germany

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Cologne, 51109, Germany

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Gauting, 82131, Germany

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Hamburg, 20251, Germany

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Jena, 07747, Germany

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Kassel, 34125, Germany

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Ancona, 60126, Italy

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Bari, 70124, Italy

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Milan, 20141, Italy

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Napoli, 80131, Italy

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Orbassano, 10043, Italy

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Palermo, 90146, Italy

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Roma, 00168, Italy

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Adapazarı, 54290, Turkey (Türkiye)

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Ankara, 06010, Turkey (Türkiye)

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Ankara, 06100, Turkey (Türkiye)

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Ankara, 06800, Turkey (Türkiye)

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Antalya, 07070, Turkey (Türkiye)

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Bursa, 16059, Turkey (Türkiye)

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Edirne, 22030, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Research Site

Istanbul, 34722, Turkey (Türkiye)

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Research Site

Izmir, 35100, Turkey (Türkiye)

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Research Site

Malatya, 44280, Turkey (Türkiye)

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Research Site

Pamukkale, 20070, Turkey (Türkiye)

Location

Related Links

• Redacted CSP
• Redacted CSR Synopsis
• Redacted SAP

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

durvalumab; Cisplatin; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Limitations and Caveats

The study results are presented as of the final data cut-off dated April 21, 2024. After final DCO, no additional data was collected for the purpose of the analysis. The participants were allowed to continue the study drug until other drug supply options were available. The last subject's last visit was declared once all participants were transferred to a rollover study or a marketed product, which occurred on January 2, 2025 and was reported as the study completion date.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: March 1, 2021
• Study Start: November 11, 2021
• Primary Completion: June 12, 2023
• Study Completion: January 2, 2025
• Last Updated: May 23, 2025
• Results First Posted: August 20, 2024

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

IT (7); CA (1); BU (5); CZ (3); DE (7); TU (12)