Avasopasem Minimizes Radiation-Induced Esophagitis in Patients with Lung Cancer

Use of avasopasem manganese (GC4419) reduced the incidence of radiation-induced, severe esophagitis in patients with lung cancer undergoing chemoradiotherapy, according to results from the 6-week, phase 2a, open-label, single-arm AESEOP trial (NCT04225026), announced in a press release by Galera Therapeutics, Inc.¹

“These encouraging results demonstrate avasopasem’s potential to meaningfully reduce radiotherapy-induced grade 3 or worse esophagitis,” said Mel Sorensen, MD, president, and chief executive officer of Galera Therapeutics.

Results showed 35 patients completed treatment with 60 gray of intensity-modulated radiation therapy (IMRT) plus chemotherapy over the course of the 6 weeks. Of these patients, 29 patients received 5 weeks or more of the avospasem dose on the days the underwent IMRT. These 29 patients were evaluated as the pre-specified per protocol population.

Two of the 29 patients (7%) experienced grade 3 esophagitis at any time.Neither of these patients experienced grade 3 esophagitis for more than 1 week. Grade 4 or 5 esophagitis was not reported at any time during the AESOP trial. Previous data saw a 20% to 30% of patients experiencing grade 3 or 4 esophagitis. These results support that the use of avasopasem in this case is generally well tolerated. The adverse events experienced are comparable to those expected with chemoradiotherapy.

The rate of grade 2 AEs increased as the weeks on treatment continued. At week 2, there were grade 2 AEs observed in 10% of patients. At week 3, 17% of patients experienced grade 2 AEs and 3% had grade 3 AEs. At week 4, 38% of patients experienced grade 2 AEs, and at week 5, grade 2 AEs were observed in 48%. In the final week, 45% of patients had grade 2 AEs and 3% had grade 3 AEs.

Investigators in this trial screened 62 patients, then enrolled 32 patients with stage IIIA, stage IIIB, or postoperative stage IIB non-small cell lung cancer or limited-stage small cell lung cancer. Patients enrolled in this trial were identified as high risk for developing esophagitis because of the planned radiation which was to be delivered to the esophagus. Patients received 90 mg of avasopasem intravenously for 1 hour before each chemoradiotherapy treatment.² Eligible patients were required to have an ECOG performance score of 2 or higher, have adequate hematologic, renal, and liver function, and use highly effective contraception.² Assessment and classification of patients were performed under the National Cancer Institute Common Terminology for Adverse Events.³

“Patients with lung cancer undergoing chemoradiotherapy are at high risk of severe and potentially life-threatening esophagitis, including an inability to eat or swallow, severe pain, ulceration, infection, bleeding and weight loss, and there are no established drug therapies. Following the positive Phase 3 results of avasopasem in radiotherapy-induced severe oral mucositis, we believe these results in esophagitis support the safety and efficacy of avasopasem as a potential therapy to prevent the most severe forms of radiotherapy-induced toxicities,” Sorensen stated.

_References

_{1. Galera announces topline results from phase 2a aesop trial of avasopasem for chemoradiotherapy-induced esophagitis. Press release. Galera Therapeutics, Inc; May 2, 2022. Accessed May 2, 2022. https://bit.ly/3802BHl}

_{2. Effects of intravenous GC4419 on the incidence and severity of esophagitis due to chemoradiotherapy for lung cancer. ClinicalTrials.gov. Updated January 6, 2022. Accessed May 2, 2022. https://clinicaltrials.gov/ct2/show/NCT04225026?term=avasopasem+manganese&draw=2&rank=5}

_{3. Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13(3):176-181. doi:10.1016/S1053-4296(03)00031-6}