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Peer-reviewedCC BYESMO open

A randomised, open-label, phase II study of tobemstomig combinations in patients with previously untreated advanced clear-cell renal cell carcinoma.

  • B I Rini1
  • T Powles2
  • P Tomczak3
  • S J Shin4
  • J Guo5
  • J Molina-Cerrillo6
  • X Ren7
  • J L Lee8
  • P J Wysocki9
  • J Puente10
  • A Basu11
  • N Mar12
6 more authors
  • S Bernhard13
  • O Khan13
  • J Ha13
  • L Colley14
  • H Prizant15
  • L Albiges16
16 affiliations
  1. 1Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, USA. Electronic address: [email protected].
  2. 2Barts Cancer Centre, Barts Health NHS Trust, Queen Mary University of London, London, UK.
  3. 3Department of Medical Oncology, Poznań University of Medical Sciences, Poznań, Poland.
  4. 4Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
  5. 5Department of Neurology and Melanoma, Peking University Cancer Hospital and Institute, Beijung, China.
  6. 6Medical Oncology Department, Ramón y Cajal Health Research Institute (IRYCIS), CIBERONC, Alcalá University, University Hospital Ramon y Cajal, Madrid, Spain.
  7. 7Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
  8. 8Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  9. 9Department of Oncology, Jagiellonian University Medical College, Cracow, Poland.
  10. 10Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain.
  11. 11Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, USA.
  12. 12Division of Hematology and Oncology, University of California at Irvine, Irvine, USA.
  13. 13Roche Products Limited, Welwyn Garden City, UK.
  14. 14Hoffmann-La Roche, Mississauga, Canada.
  15. 15Genentech, Inc. South San Francisco, San Francisco, USA.
  16. 16Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France.
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Abstract

Background

Immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted tyrosine kinase inhibitors (TKIs) have improved advanced renal cell carcinoma (RCC) outcomes, yet median progression-free survival (PFS) remains <2 years.Patients and methods

This randomised (1 : 1 : 1), open-label, phase II study (NCT05805501) evaluated tobemstomig [bispecific anti-programmed cell death protein 1 (PD-1)/lymphocyte-activation gene 3] plus axitinib (VEGF-TKI) and tobemstomig plus tiragolumab (anti-T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains) plus axitinib versus pembrolizumab (anti-PD-1) plus axitinib (control) in patients with untreated, locally advanced unresectable/metastatic clear-cell RCC with intermediate/poor International Metastatic Renal Cell Carcinoma Database Consortium risk. Following a protocol-specified interim futility analysis that led to study termination, the primary endpoint was amended from PFS and incidence/severity of adverse events (AEs) to the latter only. Efficacy was evaluated descriptively.Results

In the safety population (198 patients: tobemstomig-axitinib, n = 66; tobemstomig-tiragolumab-axitinib, n = 65; control, n = 67), grade 3-4 AEs occurred in 62.1%, 67.7% and 56.7% of patients in the respective arms and treatment-related serious AEs occurred in 22.7%, 29.2% and 13.4%. Confirmed overall response rates were 51.5%, 53.8% and 51.5%; median PFS was 12.4 [95% confidence interval (CI) 8.4-16.3], 12.5 (95% CI 7.3-17.2) and 12.5 months (95% CI 9.5 to not estimable).Conclusions

Tobemstomig-containing regimens were associated with increased toxicity and did not demonstrate meaningful efficacy improvement relative to control.

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Cite

BibTeXRIS
BibTeX
@article{rini2026randomised,
  title = {{A randomised, open-label, phase II study of tobemstomig combinations in patients with previously untreated advanced clear-cell renal cell carcinoma.}},
  author = {B I Rini and T Powles and P Tomczak and S J Shin and J Guo and J Molina-Cerrillo and X Ren and J L Lee and P J Wysocki and J Puente and A Basu and N Mar and S Bernhard and O Khan and J Ha and L Colley and H Prizant and L Albiges},
  journal = {ESMO open},
  year = {2026},
  month = oct,
  doi = {10.1016/j.esmoop.2026.108587},
  url = {https://europepmc.org/article/MED/42849355},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - A randomised, open-label, phase II study of tobemstomig combinations in patients with previously untreated advanced clear-cell renal cell carcinoma.
AU  - B I Rini
AU  - T Powles
AU  - P Tomczak
AU  - S J Shin
AU  - J Guo
AU  - J Molina-Cerrillo
AU  - X Ren
AU  - J L Lee
AU  - P J Wysocki
AU  - J Puente
AU  - A Basu
AU  - N Mar
AU  - S Bernhard
AU  - O Khan
AU  - J Ha
AU  - L Colley
AU  - H Prizant
AU  - L Albiges
PY  - 2026
DA  - 2026/10/09
JO  - ESMO open
DO  - 10.1016/j.esmoop.2026.108587
UR  - https://europepmc.org/article/MED/42849355
AB  - Background  Immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted tyrosine kinase inhibitors (TKIs) have improved advanced renal cell carcinoma (RCC) outcomes, yet median progression-free survival (PFS) remains <2 years.Patients and methods  This randomised (1 : 1 : 1), open-label, phase II study (NCT05805501) evaluated tobemstomig [bispecific anti-programmed cell death protein 1 (PD-1)/lymphocyte-activation gene 3] plus axitinib (VEGF-TKI) and tobemstomig plus tiragolumab (anti-T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains) plus axitinib versus pembrolizumab (anti-PD-1) plus axitinib (control) in patients with untreated, locally advanced unresectable/metastatic clear-cell RCC with intermediate/poor International Metastatic Renal Cell Carcinoma Database Consortium risk. Following a protocol-specified interim futility analysis that led to study termination, the primary endpoint was amended from PFS and incidence/severity of adverse events (AEs) to the latter only. Efficacy was evaluated descriptively.Results  In the safety population (198 patients: tobemstomig-axitinib, n = 66; tobemstomig-tiragolumab-axitinib, n = 65; control, n = 67), grade 3-4 AEs occurred in 62.1%, 67.7% and 56.7% of patients in the respective arms and treatment-related serious AEs occurred in 22.7%, 29.2% and 13.4%. Confirmed overall response rates were 51.5%, 53.8% and 51.5%; median PFS was 12.4 [95% confidence interval (CI) 8.4-16.3], 12.5 (95% CI 7.3-17.2) and 12.5 months (95% CI 9.5 to not estimable).Conclusions  Tobemstomig-containing regimens were associated with increased toxicity and did not demonstrate meaningful efficacy improvement relative to control.
SN  - 2059-7029
ER  -