Atezolizumab in Large Cell Neuroendocrine Carcinoma

NCT06049966 | Completed Phase 1 FDA Drug

• 1 other identifier: UPI-2023-2304
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a rare and aggressive malignancy with limited prospective evidence to guide systemic treatment. This prospective, non-randomized, real-world study evaluated the effectiveness and safety of atezolizumab in combination with platinum-etoposide chemotherapy in treatment-naïve patients with metastatic lung-derived LCNEC. Patients who received atezolizumab were treated with carboplatin, etoposide, and atezolizumab, followed by atezolizumab maintenance in patients without disease progression for up to 24 months, or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision, whichever occurred first. Patients in the control cohort received carboplatin and etoposide alone. The main clinical outcomes were progression-free survival, overall survival, overall response rate, and duration of response. Exploratory translational analyses included plasma microRNA assessment, including miR-375 and miR-21, in available blood samples.

Conditions

Large Cell Neuroendocrine Carcinoma of the Lung

Keywords

Atezolizumab; Immunotherapy; LCNEC; Large Cell Neuroendocrine Carcinoma; Immune Checkpoint Inhibitors; miR375

Outcome Measures

Primary Outcomes (2)

• Progression-free survival

  Progression-free survival was defined as the time from treatment initiation to radiographic disease progression according to RECIST v1.1 or death from any cause, whichever occurred first. Patients without documented disease progression or death were censored at the date of last disease assessment or last follow-up.

  From treatment initiation through study completion/data cut-off, assessed up to 70 months.

• Overall survival

  Overall survival was defined as the time from treatment initiation to death from any cause. Patients alive at the time of data cut-off were censored at the date of last confirmed survival follow-up.

  From treatment initiation through study completion/data cut-off, assessed up to 70 months.

Secondary Outcomes (2)

• Overall Response Rate

  From treatment initiation through study completion/data cut-off, assessed up to 70 months.

• Duration of Response

  From treatment initiation through study completion/data cut-off, assessed up to 70 months.

Other Outcomes (3)

• Safety and tolerability

  From treatment initiation through study completion/data cut-off, assessed up to 70 months.

• Treatment-free interval

  From atezolizumab discontinuation through progression, death, or data cut-off, assessed up to 46 months.

• Exploratory plasma microRNA analysis

  Blood samples collected at predefined study time points during treatment and follow-up, assessed up to 70 months.

Study Arms (2)

Arm A

EXPERIMENTAL

Carboplatin AUC 5 on day 1 plus etoposide 100 mg/m² on days 1-3 every 21 days for 4-6 cycles, with atezolizumab 1200 mg every 21 days. Patients without disease progression after induction therapy continued atezolizumab maintenance for a maximum duration of 24 months, or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision, whichever occurred first.

Drug: Atezolizumab; Drug: Carboplatin; Drug: Etoposide

Arm B

ACTIVE COMPARATOR

Carboplatin AUC 5 on day 1 plus etoposide 100 mg/m² on days 1-3 every 21 days for 4-6 cycles, followed by observation. Subsequent treatment at disease progression was administered according to standard-of-care practice and physician judgment.

Drug: Carboplatin; Drug: Etoposide

Interventions

Atezolizumab DRUG

Atezolizumab 1200 mg intravenously every 21 days, administered with platinum-etoposide induction and continued as maintenance in non-progressing patients for up to 24 months, or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision, whichever occurred first.

Also known as: Tecentriq

Arm A

Carboplatin DRUG

SOL.INF 450MG/45ML VIAL ΒΤx1VIALx45ML

Also known as: CARBOPLATIN/HOSPIRA

Arm A; Arm B

Etoposide DRUG

ETOPOSIDE/PHARMACHEMIE SOL.INF 100MG/5ML VIAL BT x 10 VIALS x 5 ML

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed Stage IV (metastatic) or unresectable locally advanced LCNEC
• No prior treatment
• With or without brain metastasis, if symptomatic patients should be treated with WBRT first
• Performance Status ≤ 2
• Life expectancy \> 3 months
• Written informed consent
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

You may not qualify if:

• Prior treatment with chemotherapy, immunotherapy, targeted small molecule therapy, or radiation therapy (except WBRT for brain metastasis from LCNEC)
• Active or history of autoimmune disease or immune deficiency
• Treatment with systemic immunosuppressive medications with the following exceptions:
• Patients who have received acute, low-dose systemic immunosuppressant medication (≤ 10 mg/day oral prednisone or equivalent) or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor approval has been obtained.
• Major surgical procedure other than for diagnosis within 4 weeks before initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• Active malignancy or malignancy within 3 years
• Active tuberculosis
• Current severe, uncontrolled systemic disease other than cancer
• Known clinically significant liver disease
• Treatment with any other investigational agent or participation in another clinical study with therapeutic intent

Sponsors & Collaborators

• Oncology Center of Biochemical Education And Research: lead

Study Sites (3)

OCEBER

Athens, Athens, 11527, Greece

Location

Sotiria Thoracic Diseases General Hospital of Athens

Athens, 115 27, Greece

Location

National and Kapodistrian University of Athens

Athens, 11527, Greece

Location

MeSH Terms

Interventions

atezolizumab; Carboplatin; Etoposide

Intervention Hierarchy (Ancestors)

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

Study Officials

• Konstantinos N Syrigos

  National and Kapodistrian University of Athens

  STUDY CHAIR

• Georgios Evangelou

  National and Kapodistrian University of Athens

  PRINCIPAL INVESTIGATOR

• Konstantinos N Syrigos

  Konstantinos

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2023
• First Posted: September 22, 2023
• Study Start: November 1, 2019
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: July 8, 2026

Record last verified: 2026-07

Data Sharing

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

Locations

GR (3)