Dr Lombardi on Phase 1 Data With Regorafenib Plus Temozolomide and CRT for Newly Diagnosed Glioblastoma

"The safety of regorafenib combination with temozolomide and radiation therapy was very good, with no unexpected toxicity due to regorafenib. We [also] reported very interesting [preliminary efficacy] results, and the next step will be to [evaluate the regimen in] a phase 2 randomized study."

Giuseppe Lombardi, MD, PhD, the head of the Neuro-Oncology Unit at Veneto Institute of Oncology IOV-IRCCS, discussed early safety and efficacy results from the phase 1, first-in-human REGOMA-2 trial (NCT06095375). This study evaluated the combination of regorafenib plus temozolomide with or without radiotherapy in patients presenting with newly diagnosed, MGMT-methylated, IDH wild-type glioblastoma.

Lombardi explained that the trial enrolled 21 patients: 9 in cohort A and 12 in cohort B. Patients in cohort A received regorafenib plus maintenance temozolomide after standard chemoradiotherapy, while those in cohort B received regorafenib concurrently with chemoradiotherapy and continued treatment with temozolomide.

Data presented at the 2025 Society of Neuro-Oncology Annual Meeting indicated that the regimen was safe and demonstrated good pharmacokinetics, Lombardi reported. In cohort A, no dose-limiting toxicities (DLTs) were observed. Consequently, the maximum tolerated dosage (MTD) of regorafenib was determined to be the standard dose of 160 mg per day.

After the MTD was determined in the adjuvant dose-escalation cohort, cohort B examined escalating doses of regorafenib in combination with temozolomide and radiotherapy, with regorafenib given for a total of 2 cycles from the beginning of the concomitant phase.

In cohort B, two patients experienced DLTs: one case of grade 3 hypertransaminasemia and one case of grade 4 thrombocytopenia. As a result, the MTD of regorafenib in cohort B was set at 120 mg, and this was the recommended dose for further exploration in phase 2 research.