On September 8, 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 the initiation of dosing in a Phase 2 basket trial evaluating the anti-DLL4/VEGF bispecific antibody navicixizumab, alone or in combination with chemotherapy, in patients with select advanced solid tumors (Press release, OncXerna Therapeutics, SEP 8, 2022, View Source [SID1234619256]).

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The trial is a multicenter, open-label, signal finding study with cohorts in colorectal and triple negative breast cancer currently open for enrollment. The colorectal cancer cohort is evaluating navicixizumab alone and in combination with irinotecan, while the triple negative breast cancer cohort is evaluating navicixizumab alone and in combination with paclitaxel. Per the trial protocol, two additional cohorts designed to enroll patients with ovarian cancer and gastric or gastroesophageal cancer may be opened in the future.

In addition to evaluating the safety and efficacy of the studied treatment regimens, the basket trial also seeks to evaluate the potential of the Xerna TME Panel to predict clinical benefit from navicixizumab. The Xerna TME Panel is a novel RNA gene expression-based diagnostic panel developed by OncXerna. Samples will be tested using Exact Sciences Oncomap ExTra with the Xerna TME Panel to classify patient samples into one of four tumor microenvironment (TME) subtypes based on angiogenic and immune gene expression signatures. The relationship between TME subtypes and the anti-tumor activity of studied regimens will be evaluated as a secondary endpoint in the trial.

"Aberrant Notch expression is associated with poor prognosis and treatment resistance in many solid tumors, including colorectal cancer and triple-negative breast cancer. Navicixizumab simultaneously targets inhibition of DLL4, a ligand of the Notch pathway, and VEGF, making this a very attractive therapeutic strategy to evaluate," said Paul Oberstein, M.D., Director of GI Medical Oncology in the Perlmutter Cancer Center and Associate Professor of Medicine at NYU Langone Health. "We are excited to have this study underway and look forward to evaluating the potential clinical impact of navicixizumab in these settings where patients have limited treatment options and prognosis is poor."

Laura Benjamin, Ph.D., Chief Executive Officer of OncXerna, commented, "This Phase 2 trial is an important milestone for navicixizumab’s development as we seek to build on our promising ovarian cancer data and explore its potential to address unmet needs in other settings where DLL4 plays a key role in treatment resistance. As part of our company’s commitment to expand precision medicine to improve outcomes for patients, we will also evaluate the potential of the Xerna TME Panel to identify patients more likely to respond to treatment with navicixizumab."

About the Phase 2 Trial
The Phase 2 basket trial (ONCX-NAV-G201) is a multicenter, open-label, signal finding study designed to enroll up to 180 patients across four cohorts:

Colorectal Cancer Cohort: Designed to evaluate navicixizumab alone and in combination with irinotecan in patients with colorectal cancer who have failed two lines of prior standard therapy, including treatment with prior bevacizumab or an equivalent antibody. This cohort will enroll up to 60 patients.
Triple Negative Breast Cancer Cohort: Designed to evaluate navicixizumab alone and in combination with paclitaxel in patients with triple negative breast cancer who have received at least two and no more than four prior lines of standard therapy for metastatic disease. Per the trial’s inclusion criteria, prior therapy must include both an immune checkpoint inhibitor in patients with combined positive score > 10, and sacituzumab govitecan. This cohort will enroll up to 60 patients.
Gastric/Gastroesophageal Cancer Cohort: Designed to evaluate navicixizumab plus paclitaxel in patients with second-line gastric or gastroesophageal cancer whose prior therapy included an immune checkpoint inhibitor. This cohort will enroll up to 30 patients.
Ovarian Cancer Cohort: Designed to evaluate navicixizumab monotherapy in patients with relapsed/refractory ovarian cancer who have received at least two and no more than five prior lines of standard therapy. This cohort will enroll up to 30 patients.
The primary endpoints of the trial are objective response rate and progression-free survival. Key secondary endpoints include overall survival, duration of response, safety and tolerability assessments, and the relationship between tumor Xerna TME Panel biomarker subtype and the anti-tumor activity of studied regimens. Xerna TME Panel assessments will be made using formalin-fixed paraffin embedded archive or core tumor samples collected during screening. For more information on the trial, see Clinicaltrials.gov Identifier: NCT05453825.

About Navicixizumab
Navicixizumab is an anti-DLL4/VEGF bispecific antibody product candidate that demonstrated antitumor activity in patients who were previously treated with Avastin (bevacizumab) in a Phase 1b clinical trial. The U.S. Food and Drug Administration granted Fast Track designation to navicixizumab for the treatment of high-grade ovarian, primary peritoneal, or fallopian tube cancer in patients who have received at least three prior therapies and/or prior treatment with Avastin. Navicixizumab 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 ovarian cancer.

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.