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.

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.

Long-term evaluation of cardiac and vascular toxicity in patients with Philadelphia chromosome-positive leukemias treated with bosutinib.

Vascular and cardiac safety during tyrosine kinase inhibitor (TKI) therapy is an emerging issue. We evaluated vascular/cardiac toxicities associated with long-term bosutinib treatment for Philadelphia chromosome-positive (Ph+) leukemia based on treatment-emergent adverse events (TEAEs) and changes in QTc intervals and ejection fraction in two studies: a phase 1/2 study of second-/third-/fourth-line bosutinib for Ph+ leukemia resistant/intolerant to prior TKIs (N = 570) and a phase 3 study of first-line bosutinib (n = 248) versus imatinib (n = 251) in chronic phase chronic myeloid leukemia. Follow-up time was ≥48 months (both studies).

Correlation of KIT and PDGFRA mutational status with clinical benefit in patients with gastrointestinal stromal tumor treated with sunitinib in a worldwide treatment-use trial.

Background: Several small studies indicated that the genotype of KIT or platelet-derived growth factor receptor-α (PDGFRA) contributes in part to the level of clinical effectiveness of sunitinib in gastrointestinal stromal tumor (GIST) patients. This study aimed to correlate KIT and PDGFRA mutational status with clinical outcome metrics (progression-free survival [PFS], overall survival [OS], objective response rate [ORR]) in a larger international patient population.

Methods: This is a non-interventional, retrospective analysis in patients with imatinib-resistant or intolerant GIST who were treated in a worldwide, open-label treatment-use study (Study 1036; NCT00094029) in which sunitinib was administered at a starting dose of 50 mg/day on a 4-week-on, 2-week-off schedule.

Final results from the large sunitinib global expanded-access trial in metastatic renal cell carcinoma.

Background: We report final results with extended follow-up from a global, expanded-access trial that pre-regulatory approval provided sunitinib to metastatic renal cell carcinoma (mRCC) patients, ineligible for registration-directed trials.

Methods: Patients ⩾18 years received oral sunitinib 50 mg per day on a 4-weeks-on-2-weeks-off schedule. Safety was assessed regularly.