A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer

BMC Cancer · 26 authors, 8 centres

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TL;DR

No patient results have been reported; the study is ongoing with first patient inclusion on December 5th, 2022.

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629 CHARS

This is a phase I/II clinical trial protocol (NCT05259319) evaluating the combination of atezolizumab (anti-PD-L1), tiragolumab (anti-TIGIT monoclonal antibody), and SBRT in patients with metastatic NSCLC, renal cell cancer, bladder cancer, and head and neck cancer who have been previously treated with ICIs. The phase I portion investigates two different SBRT scheduling schemes with a fixed dose of both immunotherapy agents in NSCLC patients only. The primary phase I endpoint is safety; the primary phase II endpoint is 6-month PFS. The study is ongoing; no efficacy or safety data from enrolled patients have been reported.

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other

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clinical trial

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AI pipeline

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ORIGINAL PAPER

PMC10633948

A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer

BMC Cancer

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ABSTRACT

Abstract Background Immunotherapy targeting the PD-1/PD-L1 pathway is a standard of care in a number of metastatic malignancies, but less than a fifth of patients are expected to respond to ICIs (Immune Checkpoint Inhibitors). In a clinical trial, combining the anti-TIGIT ( T cell immunoreceptor with Ig and ITIM domains ) Mab (monoclonal antibody) tiragolumab with atezolizumab improved outcomes in non-small cell lung cancer. In preclinical models, SBRT (Stereotactic Body Radiation Therapy) could increase expression levels of the inhibitory co-receptors TIGIT and PD-L1. We aim to assess the combination of tiragolumab with atezolizumab and SBRT in metastatic, previously treated by ICIs, non-small cell lung cancer, head and neck cancer, bladder cancer, and renal cell cancer. Methods This phase I study (ClinicalTrials.gov NCT05259319) will assess the efficacy and safety of the combination of atezolizumab with tiragolumab and stereotactic body radiation therapy in patients with histologically proven metastatic non-small cell lung cancer, renal cell cancer, bladder cancer, and head and neck cancer previously treated. First part: 2 different schedules of SBRT in association with a fixed dose of atezolizumab and tiragolumab will be investigated only with metastatic non-small cell lung cancer patients (cohort 1). The expansion cohorts phase will be a multicentric, open-label study at the recommended scheme of administration and enroll additional patients with metastatic bladder cancer, renal cell cancer, and head and neck cancer (cohort 2, 3 and 4). Patients will be treated until disease progression, unacceptable toxicity, intercurrent conditions that preclude continuation of treatment, or patient refusal in the absence of progression or intolerance. The primary endpoint of the first phase is the safety of the combination in a sequential or concomitant scheme and to determine the expansion cohorts phase recommended scheme of administration. The primary endpoint of phase II is to evaluate the efficacy of tiragolumab + atezolizumab + SBRT in terms of 6-month PFS (Progression-Free Survival). Ancillary analyses will be performed with peripheral and intratumoral immune biomarker assessments. Trial registration This study is registered on ClinicalTrials.gov: NCT05259319, since February 28th, 2022. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-023-11534-6. Keywords: Non-small cell lung cancer, Renal cell cancer, Bladder cancer, Head and neck cancer, PDL-1, TIGIT, Atezolizumab, Tiragolumab, Stereotactic body radiation therapy, SBRT, Immunotherapy

CITATION EXPORT

Nicolas Roussot, Jean-David Fumet, Emeric Limagne et al.. A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer. BMC Cancer. (2023). https://doi.org/10.1186/s12885-023-11534-6

AUTHORS

26 · 8 CENTRES

Nicolas Roussot, Jean-David Fumet, Emeric Limagne, Marion Thibaudin, Alice Hervieu, Audrey Hennequin, Sylvie Zanetta, Lorraine Dalens, Théo Fourrier, Loick Galland, Pierre Jacob, Aurélie Bertaut, Emilie Rederstorff, Cédric Chevalier, Sarah Ghirardi, Elodie Gilbert, Azzat Khoukaz, Etienne Martin, Constance Nicolet, Magali Quivrin, David Thibouw, Noémie Vulquin, Gilles Truc, Magali Rouffiac, Francois Ghiringhelli, Céline Mirjolet

1Department of Medical Oncology, Center Georges François Leclerc, 1 rue du Professeur Marion, Dijon, 21000 France
2Department of Radiotherapy, Center GF Leclerc, Dijon, France
3Cancer Biology Transfer Platform, Dijon, France
4GIMI Genetic and Immunology Medical Institute, Dijon, France
5University of Burgundy-Franche Comté, Dijon, France
6UMR INSERM 1231, Dijon, France
7Department of Epidemiology and Biostatistics, Center GF Leclerc, Dijon, France
8Radiation Oncology Department, Preclinical Radiation Therapy and Radiobiology Unit, Center GF Leclerc, Unicancer, Dijon, France