Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease - a randomized, open-label, multicenter phase II trial

Farastuk Bozorgmehr, Petros Christopoulos, Inn Chung, Jelena Cvetkovic, Manuel Feißt, Johannes Krisam, Marc A Schneider, Claus Peter Heußel, Michael Kreuter, Daniel W Müller, Michael Thomas, Stefan Rieken, Farastuk Bozorgmehr, Petros Christopoulos, Inn Chung, Jelena Cvetkovic, Manuel Feißt, Johannes Krisam, Marc A Schneider, Claus Peter Heußel, Michael Kreuter, Daniel W Müller, Michael Thomas, Stefan Rieken

Abstract

Background: Recently, the combination of the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab with first-line chemotherapy has demonstrated to improve outcome for patients with advanced small cell lung cancer (SCLC), leading to approval of this regimen. At the same time, accumulating (pre-)clinical data suggest synergisms of radiotherapy and immunotherapy via the radiation-mediated induction of anti-tumor immunogenicity. Combining the recent findings, the TREASURE trial aims at further enhancing response to upfront chemo-immunotherapy by the addition of thoracic radiotherapy (TRT).

Methods/design: The TREASURE trial is a randomized, multicenter, phase II clinical trial ( ClinicalTrials.gov identifier, NCT04462276). One hundred four patients suffering from extensive disease (ED) SCLC, with any response to the standard of care induction chemo-immunotherapy will be randomized to receive atezolizumab maintenance therapy with or without TRT. The primary endpoint of this study is overall survival (OS). Secondary endpoints include further measures of efficacy, safety, and the collection of biomarker samples. A safety interim analysis will take place after n = 23 patients receiving TRT have been observed for three months after the end of TRT.

Discussion: This trial will investigate whether treatment efficacy can be improved by adding TRT to atezolizumab maintenance therapy in ED SCLC patients with any response after chemo-immunotherapy. Safety and feasibility of such a regimen will be evaluated, and biomaterials for a translational research project will be collected. Together, the results of this trial will deepen our comprehension of how checkpoint inhibition and radiotherapy interact and contribute to the evolving landscape of SCLC therapy.

Trial registration: Clinicaltrials.gov identifier: NCT04462276 (Date of initial registration: 8th July 2020), https://ichgcp.net/clinical-trials-registry/NCT04462276 Eudra-CT Number: 2019-003916-29 (Date of initial registration: 30th March 2020), https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-003916-29/DE.

Keywords: Anti-PD-L1 monoclonal antibody; Atezolizumab; Extensive disease small cell lung cancer; First-line therapy; Radioimmuntherapy; SCLC; Thoracic radiotherapy.

Conflict of interest statement

There has been no financial support for this work that could have influenced its outcome. The TREASURE trial receives funding from Roche Pharma AG. However, Roche Pharma AG has not been involved in study design, data collection, management, data analysis and interpretation, or in the decision to submit this protocol for publication. All authors declare that there are no competing conflicts of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
TREASURE study design. ED SCLC patients with any response (defined as CR/PR or thoracic SD with CR/PR of extrathoracic lesions) after four cycles of standard chemo-immunotherapy consisting of carboplatin/etoposide and atezolizumab will be randomized to either receive thoracic radiotherapy or not. All patients will receive maintenance atezolizumab therapy until disease progression or occurrence of intolerable toxicities

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