Safety and preliminary efficacy of AZD1390 + radiation therapy (RT) for glioblastoma (GBM)

As per the data presented at the AACR 2024 conference, of the 21 patients who received AZD1390 in conjunction with radiation therapy at manageable doses, the median overall survival (OS) stood at 12.7 months.

In arm A, comprising 75 patients with recurrent glioblastoma, the combination therapy of AZD1390 and IMRT was well-tolerated, primarily resulting in low-grade and reversible adverse effects. Fatigue, nausea, and headache were among the common treatment-emergent adverse effects (TEAEs). In addition, the dose-limiting toxicities included skeletal muscle issues, with a maximum tolerated dose of 400 mg once daily identified for AZD1390. Overall, 9.3% of patients stopped AZD1390 and/or radiotherapy due to toxicity, and 6.7% discontinued AZD1390 alone due to adverse events. No patients ceased IMRT treatment due to therapy-related adverse effects.

In arm C, which encompassed 40 patients with unmethylated MGMT primary glioblastoma, common TEAEs consisted of fatigue, radiation-induced skin injury, headache, and nausea. Dose-limiting toxicities involved radiation-induced skin injury, leading to the determination of 300 mg once daily as the maximum tolerated dose of AZD1390 for this subgroup. Moreover, 10.0% of patients discontinued AZD1390 and/or radiation therapy due to adverse events; however, none of the patients (0%) discontinued AZD1390 solely due to toxicity. Investigators underscored the absence of treatment-related radiotherapy discontinuations in arm C.

KOL insight

“The data from this first-in-patient study demonstrated the potential for AZD1390 to act as a radiosensitizer for the treatment of glioblastoma.”–Expert Opinion

“Concurrent AZD1390 and IMRT was well tolerated with a manageable safety profile for both patients with recurrent glioblastoma as well as primary glioblastoma.”–Expert Opinion

Conclusion

The combination of AZD1390 and IMRT was well tolerated, demonstrating a manageable safety profile in patients with both recurrent and primary glioblastoma. Lastly, the early safety and efficacy data from this groundbreaking Phase I study suggest that AZD1390 holds promise as a radiosensitizing therapy for glioblastoma.