Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) -mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab. Patients and Methods Patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned at a ratio of two to one to receive seribantumab plus paclitaxel or paclitaxel alone. Patients underwent pretreatment core needle biopsy; archival tumor samples were also obtained to support biomarker analyses. Results A total of 223 patients were randomly assigned (seribantumab plus paclitaxel, n = 140; paclitaxel alone, n = 83). Median PFS in the unselected intent-to-treat population was 3.75 months with seribantumab plus paclitaxel compared with 3.68 months with paclitaxel alone (hazard ratio [HR], 1.027; 95% CI, 0.741 to 1.425; P = .864). Among patients whose tumors had detectable HRG mRNA and low HER2 (n = 57 [38%] of 151 with available biomarker data), increased treatment benefit was observed in those receiving seribantumab plus paclitaxel compared with paclitaxel alone (PFS HR, 0.37; 95% CI, 0.18 to 0.76; P = .007). The HR in patients not meeting these criteria was 1.80 (95% CI, 1.08 to 2.98; P = .023). Conclusion The addition of seribantumab to paclitaxel did not result in improved PFS in unselected patients. Exploratory analyses suggest that detectable HRG and low HER2, biomarkers that link directly to the mechanism of action of seribantumab, identified patients who might benefit from this combination. Future clinical trials are needed to validate this finding and should preselect for HRG expression and focus on cancers with low HER2 levels.

Andrés M Poveda Instituto Valenciano de Oncologia and Grupo Español de Investigación en Cáncer de Ovario Valencia

David Cibula General University Hospital Prague and Charles University Prague Czech Republic

Eric Pujade Lauraine Hôpital Hotel Dieu Université Paris Descartes and GINECO Paris

Felix Hilpert Universitätsklinikum Schleswig Holstein Kiel

Francesco Raspagliesi Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori

Frederic Selle Hôpital Tenon and GINECO

Hal Hirte Hamilton Health Sciences Juravinski Cancer Centre Hamilton Ontario Canada

Ignace Vergote University Hospital Katholieke Universiteit Leuven and Leuven Cancer Institute Leuven Belgium

Isabelle Ray Coquard Centre Léon Bérard University Claude Bernard and Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens Lyon

Isabelle Tabah Fisch and Joseph Pearlberg Sanofi Oncology

Josep Maria del Campo Hospital Universitari Vall d'Hebron and GEICO Barcelona Spain

Joyce F Liu Dana Farber Cancer Institute Boston

Laurence Gladieff Institut Claudius Regaud Institut Universitaire du Cancer de Toulouse Oncopole and GINECO Toulouse France

Philipp Harter Kliniken Essen Mitte and Arbeitsgemeinschaft Gynäkologische Onkologie Essen Germany

R Wendel Naumann Levine Cancer Institute Carolinas Medical Center Charlotte NC

Robert L Coleman MD Anderson Cancer Center Houston TX

Salvatore Siena Niguarda Cancer Center Grande Ospedale Metropolitano Niguarda and Università degli Studi di Milano Milano Italy

Victor Moyo Kaveh Riahi Rachel Nering William Kubasek Bambang Adiwijaya Akos Czibere and Gavin MacBeath Merrimack Pharmaceuticals Cambridge MA

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