PMID- 37946136
OWN - NLM
STAT- MEDLINE
DCOM- 20231113
LR  - 20231113
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 23
IP  - 1
DP  - 2023 Nov 9
TI  - A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic 
      body radiation therapy in patients with metastatic multiorgan cancer.
PG  - 1080
LID - 10.1186/s12885-023-11534-6 [doi]
LID - 1080
AB  - 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.
CI  - (c) 2023. The Author(s).
FAU - Roussot, Nicolas
AU  - Roussot N
AD  - Department of Medical Oncology, Center Georges Francois Leclerc, 1 rue du 
      Professeur Marion, Dijon, 21000, France.
AD  - Cancer Biology Transfer Platform, Dijon, France.
AD  - University of Burgundy-Franche Comte, Dijon, France.
AD  - UMR INSERM 1231, Dijon, France.
FAU - Fumet, Jean-David
AU  - Fumet JD
AD  - Department of Medical Oncology, Center Georges Francois Leclerc, 1 rue du 
      Professeur Marion, Dijon, 21000, France. jdfumet@cgfl.fr.
AD  - Cancer Biology Transfer Platform, Dijon, France. jdfumet@cgfl.fr.
FAU - Limagne, Emeric
AU  - Limagne E
AD  - Cancer Biology Transfer Platform, Dijon, France.
AD  - GIMI Genetic and Immunology Medical Institute, Dijon, France.
AD  - University of Burgundy-Franche Comte, Dijon, France.
AD  - UMR INSERM 1231, Dijon, France.
FAU - Thibaudin, Marion
AU  - Thibaudin M
AD  - Cancer Biology Transfer Platform, Dijon, France.
AD  - GIMI Genetic and Immunology Medical Institute, Dijon, France.
AD  - UMR INSERM 1231, Dijon, France.
FAU - Hervieu, Alice
AU  - Hervieu A
AD  - Department of Medical Oncology, Center Georges Francois Leclerc, 1 rue du 
      Professeur Marion, Dijon, 21000, France.
FAU - Hennequin, Audrey
AU  - Hennequin A
AD  - Department of Medical Oncology, Center Georges Francois Leclerc, 1 rue du 
      Professeur Marion, Dijon, 21000, France.
FAU - Zanetta, Sylvie
AU  - Zanetta S
AD  - Department of Medical Oncology, Center Georges Francois Leclerc, 1 rue du 
      Professeur Marion, Dijon, 21000, France.
FAU - Dalens, Lorraine
AU  - Dalens L
AD  - Department of Medical Oncology, Center Georges Francois Leclerc, 1 rue du 
      Professeur Marion, Dijon, 21000, France.
FAU - Fourrier, Theo
AU  - Fourrier T
AD  - Department of Medical Oncology, Center Georges Francois Leclerc, 1 rue du 
      Professeur Marion, Dijon, 21000, France.
FAU - Galland, Loick
AU  - Galland L
AD  - Department of Medical Oncology, Center Georges Francois Leclerc, 1 rue du 
      Professeur Marion, Dijon, 21000, France.
FAU - Jacob, Pierre
AU  - Jacob P
AD  - Department of Medical Oncology, Center Georges Francois Leclerc, 1 rue du 
      Professeur Marion, Dijon, 21000, France.
FAU - Bertaut, Aurelie
AU  - Bertaut A
AD  - Department of Epidemiology and Biostatistics, Center GF Leclerc, Dijon, France.
FAU - Rederstorff, Emilie
AU  - Rederstorff E
AD  - Department of Epidemiology and Biostatistics, Center GF Leclerc, Dijon, France.
FAU - Chevalier, Cedric
AU  - Chevalier C
AD  - Department of Radiotherapy, Center GF Leclerc, Dijon, France.
FAU - Ghirardi, Sarah
AU  - Ghirardi S
AD  - Department of Radiotherapy, Center GF Leclerc, Dijon, France.
FAU - Gilbert, Elodie
AU  - Gilbert E
AD  - Department of Radiotherapy, Center GF Leclerc, Dijon, France.
FAU - Khoukaz, Azzat
AU  - Khoukaz A
AD  - Department of Radiotherapy, Center GF Leclerc, Dijon, France.
FAU - Martin, Etienne
AU  - Martin E
AD  - Department of Radiotherapy, Center GF Leclerc, Dijon, France.
FAU - Nicolet, Constance
AU  - Nicolet C
AD  - Department of Radiotherapy, Center GF Leclerc, Dijon, France.
FAU - Quivrin, Magali
AU  - Quivrin M
AD  - Department of Radiotherapy, Center GF Leclerc, Dijon, France.
FAU - Thibouw, David
AU  - Thibouw D
AD  - Department of Radiotherapy, Center GF Leclerc, Dijon, France.
FAU - Vulquin, Noemie
AU  - Vulquin N
AD  - Department of Radiotherapy, Center GF Leclerc, Dijon, France.
FAU - Truc, Gilles
AU  - Truc G
AD  - Department of Radiotherapy, Center GF Leclerc, Dijon, France.
FAU - Rouffiac, Magali
AU  - Rouffiac M
AD  - Department of Radiotherapy, Center GF Leclerc, Dijon, France.
FAU - Ghiringhelli, Francois
AU  - Ghiringhelli F
AD  - Department of Medical Oncology, Center Georges Francois Leclerc, 1 rue du 
      Professeur Marion, Dijon, 21000, France.
AD  - Cancer Biology Transfer Platform, Dijon, France.
AD  - GIMI Genetic and Immunology Medical Institute, Dijon, France.
AD  - University of Burgundy-Franche Comte, Dijon, France.
AD  - UMR INSERM 1231, Dijon, France.
FAU - Mirjolet, Celine
AU  - Mirjolet C
AD  - UMR INSERM 1231, Dijon, France.
AD  - Radiation Oncology Department, Preclinical Radiation Therapy and Radiobiology 
      Unit, Center GF Leclerc, Unicancer, Dijon, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT05259319
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20231109
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 52CMI0WC3Y (atezolizumab)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antibodies, Monoclonal)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Non-Small-Cell Lung/radiotherapy/drug therapy
MH  - B7-H1 Antigen
MH  - *Carcinoma, Renal Cell/drug therapy
MH  - *Radiosurgery/adverse effects
MH  - *Lung Neoplasms/radiotherapy/drug therapy
MH  - *Antineoplastic Agents/therapeutic use
MH  - Antibodies, Monoclonal/adverse effects
MH  - *Kidney Neoplasms/drug therapy
MH  - *Head and Neck Neoplasms/drug therapy
MH  - *Urinary Bladder Neoplasms/drug therapy
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
PMC - PMC10633948
OTO - NOTNLM
OT  - Atezolizumab
OT  - Bladder cancer
OT  - Head and neck cancer
OT  - Immunotherapy
OT  - Non-small cell lung cancer
OT  - PDL-1
OT  - Renal cell cancer
OT  - SBRT
OT  - Stereotactic body radiation therapy
OT  - TIGIT
OT  - Tiragolumab
COIS- The authors declare no competing interests.
EDAT- 2023/11/10 06:45
MHDA- 2023/11/13 06:42
PMCR- 2023/11/09
CRDT- 2023/11/10 00:01
PHST- 2023/02/24 00:00 [received]
PHST- 2023/10/16 00:00 [accepted]
PHST- 2023/11/13 06:42 [medline]
PHST- 2023/11/10 06:45 [pubmed]
PHST- 2023/11/10 00:01 [entrez]
PHST- 2023/11/09 00:00 [pmc-release]
AID - 10.1186/s12885-023-11534-6 [pii]
AID - 11534 [pii]
AID - 10.1186/s12885-023-11534-6 [doi]
PST - epublish
SO  - BMC Cancer. 2023 Nov 9;23(1):1080. doi: 10.1186/s12885-023-11534-6.