American Association for Cancer Research (AACR 2024) April 5-10, 2024 - part 2

Dr. Aminur Rahman

Dr. Aminur Rahman presented the results from interim analysis of the Phase IB/II clinical trial, (BORTEM-17 ClinicalTrials.gov Identifier: NCT03643549). The abstract entitled ‘Biological mechanisms underlying objective responses in recurrent GBM patients treated with sequential bortezomib and temozolomide: An interim analysis of NCT03643549 Phase IB/II trial’ was accepted as an oral presentation in a clinical trials plenary Session: Biomarkers: Quantifying Pharmacodynamic Modulation.

The study investigated sequential bortezomib (BTZ) and temozolomide (TMZ) therapy for recurrent glioblastoma (GBM) patients with unmethylated MGMT promoter. Preliminary findings from the interim analysis of the first 15 patients revealed that 27% attained objective radiological responses of stable disease or better, wherein amplified EGFR appeared predictive biomarker for response. Augmented EGFR, in absence of other mutations, may preferentially result in NFκB activation that is the target for Bortezomib. NFκB  transcription factor activated MGMT protein transcription, so its inhibition by BTZ might lead to reduce MGMT protein and sensitize to temozolomide chemotherapy. Responders showed increased markers of cell death apoptosis and activated immune responses. The trial is open and recruiting the few remaining patients in Phase II.

Abstract: https://aacrjournals.org/cancerres/article/84/7_Supplement/CT019/742223

This work attracted attention.  We were interviewed and our work featured amongst the highlighted presentations at  the conference by the  AACR organizers.