Introduction/Background*No biomarkers have been established yet to predict response to anti-angiogenic treatment. To test whether the Xerna™ TME Panel, a novel biomarker, is predictive of anti-angiogenic treatment outcome, an exploratory, retrospective analysis of the Phase 1b study of navicixizumab in combination with paclitaxel in platinum resistant ovarian cancer was performed. Navicixizumab is a bispecific anti-angiogenic antibody to vascular endothelial growth factor (VEGF) and delta-like ligand 4. The Xerna™ TME Panel evaluates RNA gene expression data of ~100 genes defining the immune and angiogenic biologies that dominate the tumor microenvironment (TME). This novel diagnostic employs a machine learning model to classify a patient’s TME along immune and angiogenic axes, resulting in classification into one of four TME subtypes—Angiogenic (A), Immune Suppressed (IS), Immune Active (IA) and Immune Desert (ID). We hypothesized that patient TME subtypes classified with angiogenic dominant biology (A/IS) are more likely to benefit from treatment with navicixizimab relative to those in the biomarker negative subgroup (IA/ID).

Methodology The Phase 1b study of navicixizumab (3 mg/kg or 4 mg/k, IV, q2w) in combination with paclitaxel (80 mg/m² IV on D0, D7, and D14 of 28-day cycle) was an open-label, non-randomized study that included 44 patients with platinum-resistant, grade 2/3 ovarian cancer. Patients received a median of 4 prior treatments (63% prior bevacizumab, 45% prior PARP). Pre-treatment tumor tissue was analyzed retrospectively using the Xerna™ TME Panel.

Result(s)*The objective response rate per RECIST 1.1 was 43.2% in the overall patient population (n=44). Responses were durable (median 6 months [95% CI, 5.4 months, not estimable]). Pre-treatment tumor tissue was available for 33 patients. In the B-positive subgroup (A/IS, n=13), 62% of patients had an objective response, compared to 25%, in the B-negative subgroup (IA/ID, n=20). PFS was 9.2 months in the B-positive subgroup vs. 3.9 months in the B-negative subgroup, HR = 0.43 [95% CI 0.188 to 0.999]).

Conclusion*Navicixizumab plus paclitaxel demonstrated promising clinical activity in this heavily pretreated patient population. The Xerna™ TME Panel may identify patients more likely to benefit from treatment with navicixizumab and should be prospectively evaluated in a future study.