TY - JOUR T1 - Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2020-001395 VL - 8 IS - 2 SP - e001395 AU - Julius Strauss AU - Margaret E Gatti-Mays AU - Byoung Chul Cho AU - Andrew Hill AU - Sébastien Salas AU - Edward McClay AU - Jason M Redman AU - Houssein A Sater AU - Renee N Donahue AU - Caroline Jochems AU - Elizabeth Lamping AU - Andrea Burmeister AU - Jennifer L Marté AU - Lisa M Cordes AU - Marijo Bilusic AU - Fatima Karzai AU - Laureen S Ojalvo AU - Genevieve Jehl AU - P Alexander Rolfe AU - Christian S Hinrichs AU - Ravi A Madan AU - Jeffrey Schlom AU - James L Gulley Y1 - 2020/12/01 UR - http://jitc.bmj.com/content/8/2/e001395.abstract N2 - Background Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor (TGF)-βRII (a TGF-β ‘trap’) fused to a human IgG1 mAb blocking programmed cell death ligand 1. This is the largest analysis of patients with advanced, pretreated human papillomavirus (HPV)-associated malignancies treated with bintrafusp alfa.Methods In these phase 1 (NCT02517398) and phase 2 trials (NCT03427411), 59 patients with advanced, pretreated, checkpoint inhibitor-naive HPV-associated cancers received bintrafusp alfa intravenously every 2 weeks until progressive disease, unacceptable toxicity, or withdrawal. Primary endpoint was best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1; other endpoints included safety.Results As of April 17, 2019 (phase 1), and October 4, 2019 (phase 2), the confirmed objective response rate per RECIST V.1.1 in the checkpoint inhibitor-naive, full-analysis population was 30.5% (95% CI, 19.2% to 43.9%; five complete responses); eight patients had stable disease (disease control rate, 44.1% (95% CI, 31.2% to 57.6%)). In addition, three patients experienced a delayed partial response after initial disease progression, for a total clinical response rate of 35.6% (95% CI, 23.6% to 49.1%). An additional patient with vulvar cancer had an unconfirmed response. Forty-nine patients (83.1%) experienced treatment-related adverse events, which were grade 3/4 in 16 patients (27.1%). No treatment-related deaths occurred.Conclusion Bintrafusp alfa showed clinical activity and manageable safety and is a promising treatment in HPV-associated cancers. These findings support further investigation of bintrafusp alfa in patients with advanced, pretreated HPV-associated cancers. ER -