Professor David Goldstein has presented results from the Australasian Gastro-Intestinal Trials Group’s INTEGRATE IIb study at the 2025 European Society for Medical Oncology (ESMO) Congress.
This global phase 3 intergroup trial tested whether combining the immunotherapy drug nivolumab with the oral multi-kinase inhibitor regorafenib, could improve overall survival for patients with advanced gastric and gastro-oesophageal junction cancer that had progressed after at least two lines of chemotherapy.
About the trial:
- Design: A randomised, international phase 3 trial.
- Population: Participants with refractory advanced gastric or gastro-oesophageal junction cancer who had received ≥2 prior lines of chemotherapy, including a platinum agent and fluoropyrimidine.
- Intervention: Regorafenib plus nivolumab (RegoNivo) compared with investigator’s choice chemotherapy (taxane, irinotecan, or trifluridine/tipiracil).
- Endpoints: The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), objective response rate (ORR), quality of life, and safety.
Background
Gastric and gastro-oesophageal junction cancers remain highly aggressive diseases with limited effective treatment options once standard chemotherapy is no longer effective. Early-phase data suggested that the RegoNivo combination had antitumour activity and manageable safety, warranting investigation in a definitive trial.
Results
While progression-free survival in both groups was similar (1.9 v 1.9 months), the results show that the combination of regorafenib and nivolumab did not improve median overall survival when compared to currently used chemotherapies (median 5.9 v 6.3 months, hazard ratio [HR] 0.88, 95% CI 0.71–1.09, P = 0.23). ORR was higher in RegoNivo (7.4%) compared to CT (2.6%), as was median duration of response (9.5 v 5.6 months). Other results showed that disease control rate (DCR) was higher in RegoNivo overall (39% v 26%) and at 12-months (14% v 0%), and that deterioration-free survival based global QoL or death was prolonged with RegoNivo (HR 0.74, 95% CI 0.60–0.91).
The INTEGRATE IIb study results mark an important step forward in understanding how to treat this aggressive disease and encourage the search for more effective non-chemotherapy combinations with regorafenib.
Acknowledgements
INTEGRATE IIb was led by Professors David Goldstein, Nick Pavlakis and Kohei Shitara. The study was sponsored by the Australasian Gastro-Intestinal Trials Group (AGITG) and conducted in collaboration with the NHMRC Clinical Trial Centre, University of Sydney, Australia. Regional coordinating centres included: Syneos Health UK Limited in Korea and Japan; The Frankfurt Institute of Clinical Cancer Research IKF and Arbeitsgemeinschaft Internistische Onkologie (AIO) in Germany, Austria, Spain and Italy; Mayo Clinic – Academic and Community Cancer Research United in the United States of America; and Taiwan Cooperative Oncology Group, and the National Health Research Institutes in Taiwan. Bayer Healthcare Pharmaceuticals provided the study drug, regorafenib, and Bristol Myers Squibb provided the study drug, nivolumab.