Utomilumab in Patients With Immune Checkpoint Inhibitor-Refractory Melanoma and Non-Small-Cell Lung Cancer.

Section Head: Clinical/translational cancer immunotherapy.

Background: The goal of this study was to estimate the objective response rate for utomilumab in adults with immune checkpoint inhibitor (ICI)-refractory melanoma and non-small-cell lung cancer (NSCLC).

Methods: Utomilumab was dosed intravenously every 4 weeks (Q4W) and adverse events (AEs) monitored.

Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial.

In a recent phase 3 randomized trial of 700 patients with advanced urothelial cancer (JAVELIN Bladder 100; NCT02603432 ), avelumab/best supportive care (BSC) significantly prolonged overall survival relative to BSC alone as maintenance therapy after first-line chemotherapy. Exploratory biomarker analyses were performed to identify biological pathways that might affect survival benefit. Tumor molecular profiling by immunohistochemistry, whole-exome sequencing and whole-transcriptome sequencing revealed that avelumab survival benefit was positively associated with PD-L1 expression by tumor cells, tumor mutational burden, APOBEC mutation signatures, expression of genes underlying innate and adaptive immune activity and the number of alleles encoding high-affinity variants of activating Fcγ receptors.

Standard machine learning approaches outperform deep representation learning on phenotype prediction from transcriptomics data.

Background: The ability to confidently predict health outcomes from gene expression would catalyze a revolution in molecular diagnostics. Yet, the goal of developing actionable, robust, and reproducible predictive signatures of phenotypes such as clinical outcome has not been attained in almost any disease area. Here, we report a comprehensive analysis spanning prediction tasks from ulcerative colitis, atopic dermatitis, diabetes, to many cancer subtypes for a total of 24 binary and multiclass prediction problems and 26 survival analysis tasks.

First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20 Non-Hodgkin Lymphomas.

Purpose: In this phase I study (NCT01307267), we evaluated safety, pharmacokinetics, clinical activity, and pharmacodynamics of treatment with utomilumab plus rituximab in patients with relapsed/refractory follicular lymphoma (FL) and other CD20 non-Hodgkin lymphomas (NHL).

Patients And Methods: Primary objectives were to assess treatment safety and tolerability for estimating the MTD, using a modified time-to-event continual reassessment method, and selecting the recommended phase II dose (RP2D).

Results: Sixty-seven patients received utomilumab (0.

A phase Ib study of utomilumab (PF-05082566) in combination with mogamulizumab in patients with advanced solid tumors.

Background: Expressed on activated T and natural killer cells, 4-1BB/CD137 is a costimulatory receptor that signals a series of events resulting in cytokine secretion and enhanced effector function. Targeting 4-1BB/CD137 with agonist antibodies has been associated with tumor reduction and antitumor immunity. C-C chemokine receptor 4 (CCR4) is highly expressed in various solid tumor indications and associated with poor prognosis.

Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer.

Utomilumab (PF-05082566) is an agonistic mAb that engages the immune costimulatory molecule 4-1BB/CD137. In this first-in-human, phase I, open-label, multicenter, multiple-dose study (NCT01307267) we evaluated safety, tolerability, pharmacokinetics, preliminary clinical activity, and pharmacodynamics of single-agent utomilumab in patients with advanced malignancies. Dose escalation was based on a standard 3+3 design for doses of utomilumab from 0.

Immunocytokines: amplification of anti-cancer immunity.

Many cancers elicit an anti-tumor immune response, which is nevertheless unable to protect the patient. One approach to boost anti-tumor immunity is to target immunostimulatory cytokines to the tumor. Such targeting can be achieved by generating chimeric proteins (immunocytokines) in which the cytokine in question is fused to the C-terminus of a tumor-specific antibody.