Related Experiment Video
Updated: Jul 19, 2025
Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
Phase I Study of Entinostat, Atezolizumab, Carboplatin, and Etoposide in Previously Untreated Extensive-Stage Small
Ryan D Gentzler1, Liza C Villaruz2, John C Rhee2
1Division of Hematology/Oncology, Department of Medicine, University of Virginia Cancer Center, Charlottesville, VA, USA.
Background:
CREBBP and EP300 mutations occur at a frequency of 15% and 13%, respectively, in small cell lung cancer (SCLC), and preclinical models demonstrated susceptibility to targeting with HDAC inhibitors.
Methods:
Patients with treatment-naïve extensive-stage SCLC, ECOG ≤2 were enrolled and treated with entinostat orally weekly (4 dose levels, DL) in combination with standard dose carboplatin, etoposide, and atezolizumab. Cohort allocation was determined by Bayesian optimal interval (BOIN) design targeting an MTD with a DLT rate of 20%.
Results:
Three patients were enrolled and treated at DL1 with entinostat 2 mg. Patients were aged 69-83; 2 male, 1 female; 2 were ECOG 1, and 1 was ECOG 0. The most common adverse events (AEs) were anemia (3), neutropenia (3), thrombocytopenia (2), leukopenia (2), and hypocalcemia (2). Two experienced DLTs during cycle 1: (1) grade (Gr) 4 febrile neutropenia, and (1) Gr 5 sepsis. BOIN design required stopping accrual to DL1, and the trial was closed to further accrual. Entinostat and atezolizumab pharmacokinetics were both comparable to historical controls.
Conclusion:
Addition of entinostat to atezolizumab, carboplatin, and etoposide is unsafe and resulted in early onset and severe neutropenia, thrombocytopenia. Further exploration of entinostat with carboplatin, etoposide, and atezolizumab should not be explored. (ClinicalTrials.gov Identifier: NCT04631029).
Insights
This study found that adding entinostat to standard SCLC chemotherapy and atezolizumab was unsafe, causing severe neutropenia and thrombocytopenia. Further trials with this combination are not recommended due to toxicity concerns.
Area of Science:
- Oncology
- Pharmacology
Background:
- Small cell lung cancer (SCLC) exhibits frequent CREBBP and EP300 mutations.
- Preclinical data suggest HDAC inhibitors may be effective in SCLC.
Purpose of the Study:
- To evaluate the safety and tolerability of entinostat in combination with carboplatin, etoposide, and atezolizumab in treatment-naïve extensive-stage SCLC patients.
- To determine the maximum tolerated dose (MTD) of entinostat in this combination regimen.
Main Methods:
- A Phase I clinical trial using a Bayesian optimal interval (BOIN) design enrolled patients with treatment-naïve extensive-stage SCLC.
- Patients received escalating doses of entinostat weekly in combination with standard carboplatin, etoposide, and atezolizumab.
- Dose-limiting toxicities (DLTs) were monitored to identify the MTD.
Main Results:
- Three patients were enrolled at the lowest dose level (2 mg entinostat).
- Two patients experienced dose-limiting toxicities: grade 4 febrile neutropenia and grade 5 sepsis.
- The trial was stopped due to unacceptable toxicity, with common adverse events including anemia and neutropenia.
Conclusions:
- The combination of entinostat with carboplatin, etoposide, and atezolizumab is not safe for extensive-stage SCLC.
- Severe and early-onset neutropenia and thrombocytopenia were observed.
- Further investigation of this specific combination regimen is not recommended.
More Related Videos
05:11Author Spotlight: Establishing a Murine Non-Small Cell Lung Cancer Model for Developing Nanoformulations of Anticancer Drugs
Published on: May 10, 2024
07:42Patient-Derived Tumor Explants As a "Live" Preclinical Platform for Predicting Drug Resistance in Patients
Published on: February 7, 2021
