Non-Small Cell Lung Cancer
Conditions
Keywords
Advanced Non-Small Cell Lung Cancer, NSCLC Rare Histological Subtypes
Brief summary
This study is aimed to explore the antitumor activity and the safety profile of atezolizumab in pretreated advanced NSCLC patients with rare histological subtypes.
Interventions
DRUGAtezolizumab
Atezolizumab will be administered on Day 1 every 21 days (+/- 3 days).
Sponsors
AOU S.Orsola Malpighi-Unit of Oncologic Molecular and Transplantations Pathology
Istituto Toscano Tumori
YGHEA, CRO Division of Ecol Studio spa
Iqvia Pty Ltd
AOU S. Orsola Malpighi - Clinical Trial Office
Silvano Chiapparoli Logistica SpA
Roche SpA
Gruppo Oncologico Italiano di Ricerca Clinica
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, open label clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Locally advanced, relapsed or metastatic non-small cell lung cancer (NSCLC) - stage IIIB/IV according to 7th International Association for the Study of Lung Cancer (IASLC) classification * Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) with rare histological subtype, according to World Health Organization (WHO) 2015 classification. Histologic subtype variants to be enrolled into the study include: colloid adenocarcinoma (or adenocarcinoma with colloid features); fetal adenocarcinoma (or adenocarcinoma with fetal features); large cell carcinoma (LCC); sarcomatoid carcinoma (pleomorphic, spindle cell, and/or giant cell carcinoma, carcinosarcoma, pulmonary blastoma); salivary gland-type tumors (mucoepidermoid carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma), other and unclassified carcinomas (lymphoepithelioma-like carcinoma, NUT-nuclear protein in testis-carcinoma) * Availability of tumor sample (material obtained from core-biopsy or surgical specimen) for central pathology revision is mandatory * Availability of a formalin-fixed, paraffin-embedded (FFPE) tumor block or 7-10 unstained tumor slides suitable for PD-L1 expression assessment is mandatory. The assessment of PD-L1 expression will be performed by using both SP-142 and SP-263 antibody assays. The collection of tumor sample should be performed before patients are enrolled into the study * Male and female and ≥ 18 years of age * Life expectancy ≥ 12 weeks * Progressive disease after or during at least one previous standard chemotherapy line * Measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1); clear radiological evidence of disease progression after previous treatment has to be documented * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 * Patients with treated brain metastases with stable lesions for at least 2 weeks either off steroids or on a stable dose or decreasing dose of steroids (≤ 10 mg prednisone or equivalent daily) will be enrolled. Radiotherapy must have been completed a minimum of 14 days prior to registration, and patients must have recovered from adverse events (AEs) related to radiotherapy to \< grade 1 (except alopecia) * For Females: must be postmenopausal for at least 1 year before the screening visit, or are surgically sterile or not sexually active. Women of childbearing potential (WOCBP) must use 2 effective methods of contraception with a failure rate of less than 1% per year, during the entire study treatment period and for a period of 5 months after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. WOCBP must have a negative serum pregnancy test during the screening period * Adequate haematological function defined by white blood cell (WBC) count ≥2,500/mm3 with absolute neutrophil count (ANC) ≥1,500/mm3, platelet count - Adequate hepatic function defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN) range (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL), serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 if liver function test elevations are due to liver metastases) * Adequate renal function defined by a serum creatinine ≤ 1.5 x ULN or an estimated creatinine clearance of ≥ 30 mL/minute for patients with creatinine levels above institutional limits (if using the Cockcroft-Gault formula) * Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/
Exclusion criteria
* Recovered (i.e., ≤ Grade 1 toxicity) from effects of prior anticancer therapy, except alopecia * Ability to comply with protocol requirements * The patient is able to provide written informed consent. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that the patient may withdraw consent at any time without prejudice to future medical care.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | From the start of treatment (baseline) to the progression of disease (PD) or trial discontinuation whichever occurs first, assessed up to 24 months. | Proportion of patients presenting Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) based on the Investigator's assessment according to standard RECIST criteria v.1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Safety based on Adverse Events Frequency and Safety | From the treatment start to 90 days after the administration of the last treatment dose. The outcome is assessed up to a maximum of 27 months. | Frequency and Severity of Adverse Events, the latter measured by each Investigator according to NCI Common Terminology Criteria for Adverse Events, version 4.03 |
| Objective Response Rate (ORR) | From the start of treatment (baseline) to the progression or stability of disease assessed up to 24 months. | Proportion of patients presenting Complete Response (CR) or Partial Response (PR) based on Investigator's assessment according to standard RECIST criteria v.1.1. |
| Overall Survival (OS) | From the date of enrollment to the date of death from any cause. The survival follow-up will continue until 6 months after the last subject receives the last dose of atezolizumab | Time from enrollment until death from any cause |
| Time To Progression (Time To Progression) | From the date of enrollment to the date of objective tumor progression assessed up to 24 months. | Time from enrollment until objective tumor progression assessed by the Investigators according to standard RECIST criteria v.1.1. |
| Progression Free Survival (PFS) | From the date of enrollment to the date of objective disease progression or death assessed up to 24 months. | Time from enrollment until objective tumor progression or death from any cause or the last date the patient was known-to be progression free or alive |
Other
| Measure | Time frame | Description |
|---|---|---|
| Predictable value of PD-L1 TILs expression on tumor response | Up to 48 months from the treatment start | Statistical analysis will be performed to evaluate the role of PD-L1 expression on immune cells as predictive biomarker of tumor response |
| Duration of Response (DoR) | From the time of documentation of tumor response to the time of disease progression assessed up to 24 months after baseline | Time from documentation of tumor response (CR or PR) to tumor progression assessed by the Investigators according to standard RECIST 1.1 criteria |
| Accuracy of antibody assays SP-142 and SP-263 | Up to 48 months from the treatment start | It will be evaluated the accuracy of both antibody assays and statistical analysis will be performed to investigate their predictive value of response |
| Correlation between PD-L1 expression both on tumor cells and on immune cells | Up to 48 months from the treatment start | Correlation analysis will be performed with the aim to evaluate PD-L1 expression on both tumor cells and immune cells |
| Time to Response | The occurrence of a response will be assessed from baseline up to 24 months | Time from the baseline to a documented tumor response (CR or PR) assessed by the Investigators according to standard RECIST criteria v.1.1. |
| Tumor shrinkage in target lesions | Up to 36 months from the treatment start | Tumor shrinkage will be determined based on the change in the sum of the longest diameter of target lesions at each time point |
| PD-L1 marker expression on tumor tissue | Up to 48 months from the treatment start | Archival tumor tissue (FFPE tumor block or 7-10 unstained slides) will be assessed for determination of PD-L1 status on tumor cells by using both SP-142 and SP-263 antibody assays |
| Predictable value of PD-L1 tumor expression on tumor response | Up to 48 months from the treatment start | Statistical analysis will be performed to evaluate the role of PD-L1 expression on tumor cells as predictive biomarker of tumor response |
| PD-L1 marker expression on Tumor Infiltrating Lymphocytes (TILs) | Up to 48 months from the treatment start | Archival tumor tissue (FFPE tumor block or 7-10 unstained slides) will be assessed for determination of PD-L1 status on immune cells by using both SP-142 and SP-263 antibody assays |
Countries
Italy
Outcome results
None listed