Strategies for Cancer Immunotherapy Clinical Trials

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Recent accomplishments include the following: BINTRAFUSP ALFA, A BIFUNCTIONAL FUSION PROTEIN TARGETING TGF-BETA AND PD- L1, IN PATIENTS WITH HUMAN PAPILLOMAVIRUS-ASSOCIATED MALIGNANCIES. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor (TGF)-betaRII (a TGF-beta "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. In these phase 1 and phase 2 trials, 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. The confirmed objective response rate per RECIST V.1.1 in the checkpoint inhibitor-naive, full-analysis population was approximately 30% to 40% (including some complete responses); eight patients had stable disease (disease control rate, 44%). In addition, three patients experienced a delayed partial response after initial disease progression, for a total clinical response rate of approximately 35% (95% CI, 23.6% to 49.1%). Approximately 83%of patients experienced treatment-related adverse events, which were grade 3/4 in 16 patients. No treatment-related deaths occurred. 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 HPV-associated cancers. In addition, staff had been involved in the planning and analyses of the followig completed clinical studies: [] Phase 1 trial of CV301 in combination with anti-PD-1 therapy in non-squamous non-small cell lung cancer. [] A randomized phase II trial of mFOLFOX6 + bevacizumab alone or with AdCEA vaccine + avelumab immunotherapy for untreated metastatic colorectal cancer. [] Joint-predominant rheumatic complications of immune checkpoint inhibitor therapy in patients with thymic epithelial tumors. [] Enhanced neoepitope-specific immunity following neoadjuvant PD-L1 and TGF-b blockade in HPV-unrelated head and neck cancer. [] A randomized phase 2 study of bicalutamide with or without metformin for biochemical recurrence in overweight or obese prostate cancer patients (BIMET-1). [] Phase 1 open-label trial of intravenous administration of MVA-BN-brachyury-TRICOM vaccine in patients with advanced cancer. [] Dual PD-L1 and TGF-b blockade in patients with recurrent respiratory papillomatosis.