This phase Ib study evaluated the safety and efficacy of paclitaxel plus navicixizumab, a bispecific antiangiogenic antibody to vascular endothelial growth factor and delta-like ligand 4, against platinum-resistant ovarian cancer.

This open-label, nonrandomized, dose-escalation and -expansion study included 44 patients with previously treated, recurrent, platinum-resistant grade 2/3 ovarian cancer. Treatment was intravenous navicixizumab (3 mg/kg or 4 mg/kg once every 2 weeks) plus paclitaxel (80 mg/m2 intravenously on days 0, 7, and 14 of 28-day cycles). The primary and secondary objectives were to evaluate the safety and efficacy of navicixizumab plus paclitaxel. An RNA-based diagnostic panel was retrospectively used to test the hypothesis that tumors with high angiogenesis or immune-suppressed tumor microenvironment (TME) subtypes (biomarker-positive) are more likely to respond to navicixizumab than those with immune-active/-desert TME subtypes (biomarker-negative). RNA expression was analyzed in available pretreatment tumor tissue to classify 33 patients’ TME subtypes, and TME panel findings were correlated with tumor response.

The dose-escalation cohorts enrolled patients at navicixizumab doses of 3 mg/kg once every 2 weeks (n = 3) and 4 mg/kg once every 2 weeks (n = 2); 3 mg/kg was selected for expansion (n = 39). No dose-limiting toxicities occurred. The most common grade 3/4 treatment-related adverse events were hypertension (40.9%), neutropenia (6.8%), and thrombocytopenia (4.5%). Pulmonary hypertension occurred in 18.2% (grade 1-2). The overall objective response rate was 43.2% (95% CI, 28.3 to 59.0): 33.3% (95% CI, 17.3 to 52.8) in patients previously treated with bevacizumab, 64.3% (95% CI, 35.1 to 87.2) in bevacizumab-naive patients, and 62% (95% CI, 31.6 to 86.1) in biomarker-positive patients. The median duration of response was 6 months (95% CI, 5.4 months to not estimable).

Navicixizumab plus paclitaxel demonstrated promising clinical activity in bevacizumab-treated and -naive patients with platinum-resistant ovarian cancer, with manageable toxicity.

Published in Journal of Clinical Oncology (April 2022)

Siqing Fu1, Bradley R. Corr2, Kerry Culm-Merdek3, Colleen Mockbee3, Hagop Youssoufian3, Robert Stagg4, R. Wendel Naumann5, Robert M. Wenham6, Rafael D. Rosengarten7, Laura Benjamin3, Erika Paige Hamilton8, Kathleen N. Moore8,9

1 Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
2 University of Colorado Hospital, Aurora, CO
3 OncXerna Therapeutics Inc, Waltham, MA
4 OncoMed Pharmaceuticals Inc, Redwood City, CA
5 Gynecologic Oncology, Levine Cancer Institute, Atrium Health, Charlotte, NC
6 Gynecologic Oncology, Moffitt Cancer Center, Tampa, FL
7 Genialis Inc, Boston, MA
8 Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN
9 Stephenson Cancer Center at the University of Oklahoma Health Sciences, Oklahoma City, OK

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