1068 - Results of a Randomized Phase 2 Study of a Novel Superoxide Dismutase Mimetic in Patients with Multiple Brain Metastases undergoing Whole-Brain Radiotherapy
Presenter(s)
J. P. Kirkpatrick1, J. Villano2, T. Walbert3, L. M. Halasz4, D. A. Macleod5, I. Batinic-Haberle1, I. Spasojevic6, S. R. Floyd1, Z. J. Reitman1, S. Penchev7, and J. Crapo7; 1Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 2University of Kentucky/Markey Cancer Center, Lexington, KY, 3Henry Ford Cancer Institute, Detroit, MI, United States, 4Department of Radiation Oncology, University of Washington/ Fred Hutchinson Cancer Center, Seattle, WA, 5Biomimetix, Denver, CO, 6Department of Medicine, Duke University Medical Center, Durham, NC, 7Biomimetix, Inc., Greenwood Village, CO
Purpose/Objective(s): While whole-brain radiotherapy (WBRT) offers good control of brain metastases (BM), patients often experience impaired neurocognition, adversely affecting quality of life (QOL) and survival. Strategies to reduce the volume of normal brain irradiated, such as stereotactic radiosurgery (SRS) and hippocampal avoiding (HA) WBRT, may limit neurocognitive decline, but are of limited utility for patients with numerous, extensive BM. We hypothesized that the addition of BMX-001, a novel Mn porphyrin superoxide dismutase mimetic with blood-brain barrier penetrance, would reduce neurocognitive decline and improve survival in patients undergoing WBRT.
Materials/Methods: Adult patients with 5 or more BM slated to undergo WBRT (3 Gy x 10 fractions) at four institutions were screened for enrollment on this IRB-approved protocol. The initial phase consisted of a 5-patient safety lead-in with all patients receiving BMX-001 and WBRT. In the second phase, patients were randomized 1:1 to BMX-001 and WBRT vs WBRT alone, with a target enrollment of 64 patients. Patient response to treatment was assessed by neurocognitive (HVLT, COWAT, Trailmaking) and QOL testing, as well as brain MRI. BMX-001 was administered by subcutaneous injection 4 days before and after the start of WBRT and on days 1, 4, 6 and 9 of WBRT.
Results: 5 patients were enrolled in the safety lead-in phase, followed by 30 (15 in each arm) in the randomized phase 2 study from January 2019 through November 2022. The trial was closed in 2023 due to lack of accrual. In the combined two phases, the average age was 59.5 years, 77% were female, and KPS was 70-80 and 90-100 in 20 and 15 patients, respectively. The majority of patients had non-small cell lung cancer primary (51.4%), followed by 25.7% with breast cancer, 11.4% with small-cell lung cancer and 11.4% with other malignancies. One patient withdrew consent before starting treatment and of the remaining 34 patients all completed WBRT and all 20 patients on BMX-001 received drug per protocol. The most common adverse effect was mild reaction at the injection site. Twelve grade 3 (2 fatigue, 1 each nausea, weight loss, anorexia, pleural effusion, dyspnea, hypoxia, transient blindness, stroke, hypotension, hyperkalemia) and no grade 4/5 adverse events were observed . The overall survival did not differ between the two arms (13.4 vs 10.9 months median OS for BMX-001+WBRT vs WBRT alone, p=.62). Neurocognition vs baseline, assessed at 1, 3, 6 and 12 months post WBRT in 21, 18, 9 and 8 patients, respectively, did not differ significantly between the two arms.
Conclusion: BMX-001 was well-tolerated in combination with WBRT. While lack of accrual – in part due to the negative perception of WBRT versus other techniques – limited our ability to judge the efficacy of BMX-001 in this setting, future trials of this agent in appropriate brain metastases populations should be considered, particularly where SRS and HA-WBRT are not indicated.