Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, for recurrent/metastatic cervical cancer after platinum failure: primary results from a phase 2 study

Abstract PURPOSE Cervical cancer is a common and lethal cancer worldwide. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the human transforming growth factor β receptor II (TGF-βRII or TGF-β “trap”) fused via a flexible linker to the C-terminus of each heavy chain of an immunoglobulin-G1 antibody blocking programmed death-ligand 1 (PD-L1), was evaluated in women with recurrent/metastatic cervical cancer. PATIENT AND METHODS This phase 2, multicenter, international, single-arm study evaluated bintrafusp alfa monotherapy in patients with recurrent/metastatic cervical cancer with disease progression during or after platinum-based chemotherapy. Patients received 1200 mg bintrafusp alfa intravenously once every 2 weeks. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by Independent Review Committee (IRC). This trial was registered with clinicaltrials.gov (NCT04246489). RESULTS At data cutoff, 146 of 203 screened patients received ≥1 bintrafusp alfa dose. The study met its primary endpoint to have a 95% confidence interval (CI) above the ORR benchmark of 15%, with an ORR of 21.9% (95% CI 15.5-29.5) per the IRC. Of these patients, 59.4% had a durable response of ≥6 months. At data cutoff, responses were ongoing in 13/32 responders (40.6%). The most common treatment-related adverse events were anemia (17.1%), rash (14.4%), hypothyroidism (10.3%), and pruritus (10.3%). Any-cause adverse events of special interest included anemia (56.2%), bleeding events (55.5%), and immune-related adverse events. CONCLUSION This phase 2 study of bintrafusp alfa met its primary endpoint, which may support the potential of a bispecific therapy targeting TGF-β and PD-L1 in recurrent/metastatic cervical cancer.