On September 16, 2021 Oncxerna Therapeutics, Inc. ("OncXerna"), a precision medicine company using an innovative RNA-expression based biomarker platform to predict patient responses to its targeted oncology therapies, reported new clinical and biomarker data from its bavituximab program in an electronic poster at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 (Press release, OncXerna Therapeutics, SEP 16, 2021, View Source [SID1234587818]).

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Data presented in the poster are from ONCG100, an open-label Phase 2 clinical trial evaluating bavituximab, a potentially first-in-class phosphatidylserine (PS) inhibitor designed to reverse immune suppression, in combination with the PD-1 inhibitor pembrolizumab (KEYTRUDA) in patients with advanced gastric or gastroesophageal junction (GEJ) cancer. Patients participating in the trial were required to undergo pre-treatment biopsies to allow for pre-specified biomarker analysis using the Xerna TME Panel.

"Predictive biomarkers are an urgent need in gastric cancer where treatment options are limited and only a small fraction of patients’ treatment is biomarker driven," said Dr. Ian Chau, consultant medical oncologist at the Royal Marsden Hospital. "This study used OncXerna’s novel RNA expression-based algorithm to classify the biology of the tumor microenvironment of individual gastric cancer patients and prospectively test the hypothesis that patient tumors classified as having a high immune score by the Xerna TME Panel are more likely to benefit from treatment with bavituximab in combination with pembrolizumab. The results support this hypothesis by showing that the Xerna TME Panel biomarker was predictive of improved treatment response rates. This finding represents a promising new development that warrants further testing."

Key data and conclusions from the ESMO (Free ESMO Whitepaper) poster and corresponding abstract include:

Bavituximab appeared to sensitize cancers to pembrolizumab, suggesting the potential for the use of the combination for patients typically less responsive to immune checkpoint inhibitor monotherapy
Objective response rates (ORR) in:
Patients with PD-L1 combined positive score (CPS) < 1: 18% (3/17)
Patients with CPS ≥ 1: 13% (5/40)
Microsatellite stable (MSS) patients: 14% (6/43)

The Xerna TME Panel biomarker predicted treatment response
ORR in biomarker positive (B+) patients: 22% (7/32)
ORR in biomarker negative (B–) patients: 4% (1/25)
B+ patients had an increased ORR vs. B– patients across MSS, CPS ≥ 1, and CPS < 1 subgroups

The combination of bavituximab and pembrolizumab was well tolerated, with no additional toxicities observed above those expected with pembrolizumab alone
The most common toxicities observed were decreased appetite and fatigue (both, 31%), constipation (29%), and nausea (26%)
No treatment related deaths were reported
Efficacy data presented in the poster are from patients in Group 1 of the ONCG100 study, who were naïve to checkpoint inhibitor therapy. Efficacy data from Group 2 patients, who previously relapsed on checkpoint inhibitor therapy, were not presented as they are not yet mature due to the majority of these patients enrolling within three months of the data cut-off date.

Laura Benjamin, Ph.D., President and Chief Executive Officer at OncXerna, commented, "These results demonstrate the potential of bavituximab to overcome checkpoint inhibitor resistance mechanisms and highlight the predictive power of the Xerna TME Panel. Data showing that patients with CPS less than one had response rates that were similar to those of patients with CPS greater than one are particularly exciting, as patients with low CPS are typically less likely to respond to pembrolizumab monotherapy. We were also thrilled to see that biomarker positive patients had an ORR that was more than five times greater than that of biomarker negative patients. Looking forward, we plan to conduct a prospective study to confirm the anti-tumor activity of bavituximab in combination with an immune checkpoint inhibitor and the ability of the Xerna TME Panel to accurately identify patients most likely to respond. This will be an important step that we expect will further demonstrate the ability of the Xerna platform to drive the development of our precision medicine pipeline."

A link to the on-demand ESMO (Free ESMO Whitepaper) poster (#1386P), entitled: "Phase 2 Study of Bavituximab, a First-in-class Antibody Targeting Phosphatidylserine, Plus Pembrolizumab in Advanced Gastric or Gastroesophageal Junction Cancer," can be found here.

About ONCG100

ONCG100 is a Phase 2, multicenter, open-label, two-cohort global study designed to assess the safety, tolerability, and antitumor activity of bavituximab (3 mg/kg, QW) in combination with pembrolizumab (200 mg, Q3W) in patients with advanced gastric or GEJ cancer regardless of PD-L1 status who have progressed on ≥ 1 prior standard therapy. Patients were either naïve to checkpoint inhibitors (Group 1) or previously relapsed on a checkpoint inhibitor (Group 2). If known, microsatellite instability-high (MSI-H) patients were excluded. Pre-treatment biopsies were required for pre-specified biomarker analysis using the Xerna TME Panel. For more information, see ClinicalTrials.gov Identifier: NCT04099641.

About Bavituximab

Bavituximab is an antibody designed to reverse immune suppression by inhibiting phosphatidylserine (PS) signaling and is currently in Phase 2 clinical trials to treat a specific subset of patients with advanced gastric cancer to improve their response to anti-PD-1 treatment. 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). The dominant biology targeted by bavituximab may be relevant for patients with many types of solid tumors whose immune systems are too suppressed to benefit from currently available immune oncology therapies. 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) and has been developed as a clinical assay. 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.