LAUSR

The multikinase inhibitor regorafenib has shown immunomodulatory activity when combined with immunecheckpoint inhibition (ICI) in mouse models of colorectal cancer (CRC); in humans, this synergistic activity could help to overcome lack of response to ICI. Now, data from a phase I trial provide early evidence of the efficacy of regorafenib in combination with nivolumab in patients with advancedstage gastric cancer or CRC. All patients (25 with gastric cancer and 25 with CRC) had previously received ≥2 lines of treatment (96% of them with anti-angiogenic agents other than regorafenib), and all had microsatellite stable or mismatch repairproficient tumours, except one with microsatellite instability (mSI)high CRC. These patients received regorafenib 80–160 mg plus nivolumab 3 mg/kg. The maximumtolerated and optimal doses of regorafenib were established as 120 mg and 80 mg, respectively. The incidence of grade ≥3 adverse events was 44% and 27% at these dose levels, respectively, including rash in 20% and 0% of patients. One patient with gastric cancer died from treatmentrelated diabetic ketoacidosis. The objective response rate was 44% in patients with gastric cancer and 36% in those with CRC (including the patient with mSIhigh CRC). median progressionfree survival and overall survival durations were 5.6 months and 12.3 months, respectively, for patients with gastric cancer, and 7.9 months and not reached in those with CRC. The survival durations with combination therapy in this trial are longer than those reported with nivolumab or regorafenib monotherapy for gastric cancer or CRC in other trials. Nevertheless, direct comparisons can only be made in large randomized controlled trials, the results of which are awaited to determine whether regorafenib plus nivolumab could be a new treatment option for patients with advancedstage gastric cancer or CRC.