A Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung

Study Overview
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Brief Summary
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This phase II clinical trial evaluates the efficacy, safety and tolerability of Atezolizumab in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC.

Official Title
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A Phase II, Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung

Conditions
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Large Cell Neuroendocrine Carcinoma of the Lung

Intervention / Treatment
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* Drug: Atezolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Patients with locally advanced or metastatic large-cell neuroendocrine carcinoma of the lung (LCNEC) without curative treatment options (patients with mixed histology are eligible if LCNEC is the predominant histology i.e. ≥50%) Previously untreated with systemic therapy (note: patients relapsing after curative radio chemotherapy or adjuvant chemotherapy are eligible if relapse occurs ≥6 months after discontinuation of curative treatment) Planned treatment with Carboplatin or Cisplatin and Etoposide (SoC) ECOG performance status: 0-2 age ≥18 years measurable disease according to RECIST v1.1 adequate organ function defined as: ALAT/ASAT ≤2.5x ULN or ≤3.5x ULN in case of liver metastases Bilirubin ≤1.5x ULN or ≤2.5x ULN in case of liver metastases Creatinine ≤1.5x ULN or Creatinine clearance according to Cockroft-Gault >60 ml/min Neutrophils ≥1 Gpt/l, Platelets >50 Gpt/l unless caused by bone marrow carcinosis Exclusion Criteria: Symptomatic brain metastases (patients with asymptomatic brain metastases are allowed provided they are stable without steroid treatment for at least 3 weeks) Severe autoimmune disease (patients with endocrine autoimmune disorders are allowed as long as they are on stable substitution treatment) Severe uncontrolled infection Prior treatment with either Atezolizumab or other immune checkpoint inhibitor Any prior treatment for metastatic disease

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atezolizumab/Platinum/Etoposide<br>Atezolizumab/Platinum/Etoposide Platinum will be cisplatin or carboplatin at the investigators discretion. | Drug: Atezolizumab<br>* Atezolizumab (IMP) will be added to Platinum/Etoposide (Standard-of-Care). Four cycles of combined immunochemotherapy 3qw will be follows by maintenance with atezolizumab monotherapy until progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | To assess the efficacy of Atezolizumab in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC as measured by overall survival. | appr. 72 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | According to RECIST v1.1 as assessed by local investigator. | appr. 72 months | 
| Immune Objective Response Rate (iORR) | According to iRECIST as assessed by local investigator. | appr. 72 months | 
| Disease Control Rate (DCR) | According to RECIST v1.1 as assessed by local investigator. | appr. 72 months | 
| Progression Free Survival (PFS) |  | appr. 72 months | 
| Immune Progression Free Survival (iPFS) |  | appr. 72 months | 
| Duration of Response (DoR) |  | appr. 72 months | 
| Progression Free Survival (PFS) rate at one year |  | 1 year | 
| Immune Progression Free Survival (iPFS) rate at one year |  | 1 year | 
| Overall survival at one year |  | 1 year | 
| Incidence, intensity, seriousness, relationship to Atezolizumab, and outcome of adverse events graded according to NCI CTCAE (v5.0). |  | appr. 72 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer, LCNEC, Neuroendocrine Carcinoma