Salah Almokadem

INTRODUCTION: Volociximab is a first-in-class chimeric monoclonal antibody that targets α5β1 integrin. Preclinical studies have shown the ability of volociximab to inhibit tumor neoangiogenesis by blocking the interaction between α5β1 and fibronectin. Volociximab's safety profile, pharmacokinetics and pharmacodynamics have been established. Ongoing clinical trials are evaluating its efficacy in the treatment of different types of solid tumors as a single agent or in combination with chemotherapy. In this review we focus on the biological effect of volociximab and results of completed clinical trials. AREAS COVERED: This review summarizes the structures and functions of integrin α5β1 and its ligand fibronectin, provides an overview of the early development of volociximab, a targeted monoclonal antibody that specifically binds and inhibits activation of integrin α5β1, and discusses the relevant data from pre-clinical and clinical studies. EXPERT OPINION: Volociximab has been well tolerated as monotherapy or in combination with chemotherapy. It has shown promising activity in different types of cancer. Randomized trials are required to validate those early results.

8535 Background: Consolidation PD-1 inhibition after chemoradiation (chemoRT) for unresectable stage IIIA/IIIB NSCLC improves overall survival. The efficacy and safety of combining a CTLA-4 inhibitor with a PD-1 inhibitor in this setting are unknown but may further improve efficacy in this patient population. Methods: In this randomized, multi-center, phase II study, 105 pts with unresectable stage IIIA/IIIB NSCLC will receive chemoRT, then randomize 1:1 to either nivolumab 480mg IV q4 wks (nivo) or nivolumab 3mg/kg IV q2 wks + ipilimumab 1mg/kg IV q6 wks (nivo/ipi), for up to 24 wks. In this interim analysis, we assess the safety of the first 20 patients treated. Results: From 9/2017 to 11/2018, 20 patients were accrued. Characteristics of those treated on the nivo arm (n = 10) were: median age 62 years, stage IIIA/B 7/3; non-squamous/squamous 7/3; and the nivo/ipi arm (n = 10): median age 61 years; stage IIIA/B 6/4; non-squamous/squamous 7/3. Most toxicities were grade 1 or 2 and the most frequently noted grade 2 AEs included fatigue (25%), pneumonia (25%), extremity pain (20%). Adverse events reported in the Nivo only arm included 81 total events with only four grade 3 events and a single grade 4 thromboembolic event. The Nivo/Ipi arm reported 101 total AEs, with only 3 grade 3 events and a single grade 4 toxicity (amylase elevation). With respect to immune-related adverse events (irAEs), in the nivo arm there were two cases of grade 2 pneumonitis and no grade 3/ 4 events. In the nivo/ipi arm, there was one grade 2 pneumonitis, three grade 3 irAEs (pneumonitis, colitis, pancreatitis), and one asympomatic grade 4 amylase elevation. No treatment-related deaths were observed in either arm. Conclusions: There were no unexpected safety signals in the first 20 patients treated on BIG10CRC LUN 16-081. The incidence of grade 3 or higher irAEs was higher in the nivo/ipi arm, as expected, but this was manageable with the use of established guidelines. The study currently remains open to accrual (32 of 105 have been randomized as of 2/8/19). Clinical trial information: NCT03285321.