On June 3, 2022 OncXerna Therapeutics, Inc. ("OncXerna"), a precision medicine company using an innovative RNA-expression based biomarker platform to predict patient responses to its targeted oncology therapeutic candidates, reported new clinical data from an investigator-sponsored Phase 2 trial evaluating bavituximab combined with chemoradiation and adjuvant temozolomide in newly diagnosed glioblastoma (GBM) patients (Press release, OncXerna Therapeutics, JUN 3, 2022, View Source [SID1234615518]). The data, which show that the trial met its primary endpoint, will be featured in a poster at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place both virtually and in-person at the McCormick Place Convention Center in Chicago, Illinois.

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Bavituximab is a potentially first-in-class phosphatidylserine (PS) inhibitor designed to reverse immune suppression. The National Comprehensive Cancer Network (NCCN) Oncology Research Program (ORP)-funded Phase 2 investigator-sponsored trial that will be featured in the ASCO (Free ASCO Whitepaper) poster was an open-label, single-arm study in newly diagnosed IDH wild-type GBM patients that was designed to evaluate the safety and efficacy of bavituximab combined with chemoradiation and adjuvant temozolomide. Per the trial protocol, success on the primary endpoint was defined as a twelve-month overall survival rate (OS-12) of greater than or equal to 72% in evaluable patients.

"Novel approaches are needed to treat GBM, as the current standard-of-care of chemoradiation and temozolomide has historically provided an OS-12 of only 60%," said Elizabeth Gerstner, M.D., Mass General Cancer Center, the study’s lead investigator. "The Phase 2 results being presented at ASCO (Free ASCO Whitepaper) suggest bavituximab modulates the immunosuppressive GBM microenvironment, demonstrating its on-target effects. The OS-12 of evaluable patients exceeded both the study’s pre-specified criteria and the historical benchmark. Improved survival also correlated with positive changes in tumor immune cell gene expression and reductions in cerebral blood flow, which indicates that bavituximab was a contributor to treatment response and supports continued clinical evaluation in GBM."

Key data and conclusions from the ASCO (Free ASCO Whitepaper) poster include:

Efficacy data in evaluable patients (N = 33, median age of 59)

OS-12: 73% (95% confidence interval: 59% – 90%)
Median progression-free survival (PFS): 6.9 months (95% confidence interval: 6.2 – 9.7 months)
Median overall survival (OS): 15.4 months (95% confidence interval: 13.3 – 23.6 months)
Disease control rate: 91% (30/33)
Overall response rate: 12% (4/33)
Safety findings:

The studied combination was generally well tolerated. There were eight grade 3 or 4 adverse events (AEs) and no grade 5 AEs observed.
Immune profile and MRI assessments:

A statistically significant reduction of pro-tumor, immunosuppressive, myeloid-derived suppressor cells (MDSCs) was observed post-treatment
Tumor samples from patients with longer PFS and OS showed a significantly positive shift in myeloid-related gene expression
The studied combination was shown to have anti-angiogenic effects as evidenced by a post-treatment decrease in relative cerebral blood flow
Laura Benjamin, Ph.D., Chief Executive Officer of OncXerna Therapeutics, commented, "Confirming the on-target effect of bavituximab in modulating the GBM immune microenvironment is a significant finding that suggests combining bavituximab with an immune checkpoint inhibitor is a reasonable potential next step in its development. Incorporating our Xerna TME panel prospectively in a future study may further enable us to understand which patients would most likely benefit from this treatment approach as well as bavituximab’s potential to significantly improve outcomes in a setting where new treatment options are desperately needed. We look forward to discussing these latest Phase 2 data with key thought leaders as we assess next steps for bavituximab in GBM."

The Xerna TME Panel is OncXerna’s novel RNA gene expression-based diagnostic panel. It uses a machine learning-based algorithm to classify patients based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME). By utilizing the Xerna TME Panel, OncXerna aims to match a specific patient’s tumor with the drugs best suited to treat that tumor.

The ASCO (Free ASCO Whitepaper) poster (# 368), entitled, Phase 2 Trial of Bavituximab with Chemoradiation and Adjuvant Temozolomide in Newly Diagnosed Glioblastoma, will be presented during the ASCO (Free ASCO Whitepaper) Annual Meeting’s "Central Nervous System Tumors" poster session, which is taking place on June 5, 2022, beginning at 8:00 a.m. CT (9:00 a.m. ET). Following its presentation at the conference, a copy of the poster will be available on the OncXerna website here.

About the Phase 2 Trial

This study is one of three investigator-sponsored studies funded through a collaboration between the NCCN ORP and OncXerna Therapeutics. The investigator-sponsored study was led by Elizabeth Gerstner, M.D., Mass General Cancer Center. The Phase 2 trial was an open-label, single-arm study designed to evaluate the safety and efficacy of bavituximab with chemoradiation and adjuvant temozolomide in adult patients with newly diagnosed glioblastoma. The trial included 33 evaluable patients who were treated with bavituximab weekly, temozolomide daily, and chemoradiotherapy in accordance with hospital guidance. The primary endpoint of the trial was OS-12, with the trial’s pre-specified statistical analysis plan indicating an OS-12 greater than or equal to 72% would result in the null hypothesis being rejected. Secondary endpoints included progression-free survival, overall survival, radiographic response, and toxicity assessments. Exploratory assessments evaluated the immune profile in tumor tissue and peripheral blood mononuclear cells with treatment and the impact of treatment on relative cerebral flood flow. For more information, see ClinicalTrials.gov Identifier: NCT03139916.

About Bavituximab

Bavituximab is an antibody designed to reverse immune suppression by inhibiting phosphatidylserine (PS) signaling. The mechanism of action of bavituximab is to block tumor immune suppression signaling from PS to multiple immune cell receptor families (e.g., TIMs and TAMs). This biology is relevant across multiple types of solid tumors. A Phase 2 clinical trial is evaluating the combination of bavituximab with KEYTRUDA to test the hypothesis that relieving immunosuppression can enhance responses to checkpoint inhibitors. Bavituximab is an investigational agent that has not been approved, and it has not been demonstrated to be safe or effective for any use, including for the treatment of advanced gastric cancer.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

About the Xerna TME Panel

The Xerna TME Panel uses proprietary RNA-based gene expression data and a machine learning-based algorithm to classify patients based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME). The Xerna TME Panel is an investigational assay that has not been approved and has not been demonstrated to be safe or effective for any use.