On April 21, 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 peer-reviewed publication of results from a Phase 1b trial evaluating navicixizumab, an anti-DLL4/VEGF bispecific antibody, combined with paclitaxel, in patients with platinum-resistant ovarian cancer (PROC) (Press release, OncXerna Therapeutics, APR 21, 2022, View Source [SID1234612760]). The paper, entitled, "Phase Ib Study of Navicixizumab Plus Paclitaxel in Patients With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer," was published in Journal of Clinical Oncology and can be found here.

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Featured in the paper are efficacy and safety data from the trial as well as correlative biomarker results generated with OncXerna’s novel RNA gene expression-based diagnostic panel, the Xerna TME Panel. The Xerna TME Panel uses a machine learning-based algorithm to assign scores based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME). Given navicixizumab’s anti-angiogenic mechanism of action, patients with high Xerna TME Panel angiogenesis scores were classified as biomarker positive (B+), while those with low angiogenesis scores were classified as biomarker negative (B-).

"This prestigious publication highlights the encouraging, durable clinical activity of navicixizumab in a heavily pretreated platinum resistant ovarian cancer patient population where the treatment options are very limited," said Kathleen Moore, M.D., Professor at The Stephenson Cancer Center, The University of Oklahoma. "In addition to seeing activity regardless of prior treatments, this study showed the potential of the Xerna TME panel to address the unmet need for a predictive biomarker for response to anti-angiogenic treatment."

Key data and conclusions from the paper include:

Navicixizumab plus paclitaxel showed promising and durable clinical activity in a heavily pretreated patient population regardless of prior treatment (median of four prior therapies)
Overall response rate (ORR) across all evaluable patients: 43% (19/44)
ORR in patients previously treated with bevacizumab (Avastin): 33% (10/30)
ORR in patients previously treated with a PARP inhibitor: 45% (9/20)
11 of 19 patients with partial or complete response had progressive disease as best response to immediate prior therapy
Median duration of response: 6 months
B+ classification showed enrichment of patients with tumor response
ORR in B+ vs. B- patients: 62% (8/13) vs. 25% (5/20)
Best response of progressive disease in B+ vs. B- patients: 0% (0/13) vs. 30% (6/20)
Median progression-free survival in B+ vs. B- patients: 9.2 months vs. 3.9 months
The safety profile of navicixizumab plus paclitaxel was consistent with known toxicities with no new safety signals or unexpected safety findings. The monitoring and management plan for hypertension and pulmonary hypertension was effective in reducing risk of severe toxicity and showed recovery upon treatment discontinuation. No grade 3 pulmonary hypertension or grade 4 hypertension reported. Treatment related adverse events led to discontinuation in 9% (4/44) of patients.
Laura Benjamin, Ph.D., Chief Executive Officer of OncXerna Therapeutics, commented, "We are thrilled with both the strength of our data and the external validation that comes from its publication in such a high-impact journal. Biomarkers to improve the selection of patients who are more likely to respond to therapy and prevent those less likely to respond from receiving an ineffective late-stage treatment are an important unmet need for cancer patients. This study provides proof of principle for further development of navicixizumab, a drug designed to address resistance to anti-VEGF and chemotherapies, as well as the potential of the Xerna TME panel to provide a predictive biomarker for anti-angiogenic treatment. To confirm this finding, the Xerna TME Panel will be used to stratify patients enrolled in a planned Phase 3 study."

OncXerna’s planned Phase 3 study, REVELARE, is designed as an open-label, randomized study of navicixizumab ± paclitaxel vs. paclitaxel monotherapy in pretreated PROC patients stratified by Xerna TME Panel biomarker status. Additional information on this planned trial can be found using ClinicalTrials.gov identifier NCT05043402.

About the Phase 1b Trial

The Phase 1b trial was an open-label, non-randomized, dose-escalation and expansion study of the safety, tolerability, and efficacy of navicixizumab plus paclitaxel in patients with platinum-resistant ovarian cancer. The trial enrolled patients who previously received Avastin (bevacizumab) and/or more than two prior lines of therapy. Patients were treated with navicixizumab once every two weeks together with weekly paclitaxel. The primary endpoint of the trial was incidence of dose limiting toxicities. Secondary endpoints included response rate assessed by RECIST criteria 1.1 and progression-free survival. For more information, see ClinicalTrials.gov Identifier: NCT03030287.

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 previously received Avastin and/or more than 2 prior lines of therapy. 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.