Phase Ib safety trial of CVX-060, an intravenous humanized monoclonal CovX body inhibiting angiopoietin 2 (Ang-2), with sunitinib.

Abstract

3032 Background: CVX-060 (CVX) is a humanized monoclonal antibody fused to two Ang2 binding peptides. The recommended phase 2 dose (RP2D) is15 mg/kg/wk by intravenous (IV) infusion. Sunitinib (Sun), a kinase with many targets including VEGFR1-3, is dosed 50 mg/day orally x 4/6 wks. Methods: Patients (pts) with solid tumors were to receive CVX at doses of 6, 12, or 15 mg/kg/wk with Sun 50 mg/day x 4/6 wks in successive cohorts. Standard definitions of dose limiting toxicities (DLTs) were used. Serum PK was assessed by ELISA. Results: Thirty-four pts were treated at 5 dose levels (DL) –see table. The median age was 62 years (29-76), ECOG performance status 0-1. The safety of CVX plus lower Sun dose was established in DL 1.1 due to DLTs at the initial cohort. The safety of full dose Sun was further established in 1.2 before further escalating the CVX dose. Overall, DLTs related to CVX and Sun included hemorrhage (DL 1.0), asymptomatic proteinuria (DL 1.2), ischemic colitis/lower GI bleed/recurrent lower GI bleed (DL 3.0) and abdominal pain/microperforation on CT (DL 3.0). The most common adverse events (AEs) related to either agent were fatigue (68%), diarrhea (50%), nausea (47%), hypertension (35%), and dysgeusia (32%). The majority of AEs were Gr 1 to 2. There were no PK interactions between CVX and Sun. Total serum Ang2 (bound plus free) increased with CVX treatment. Of the 34 patients, 24 (71%) remained on study ≥ 8 weeks and 2 patients continue on treatment ≥ 9 months. Anti-drug antibodies were seen in 16 patients at low titers without effects on PK or safety. Conclusions: In pts with advanced disease, CVX is able to be combined at the RP2D with Sun at its labeled dose without exacerbation of Sun-associated toxicities. Combination trials of CVX and other VEGF inhibitors are planned. [Table: see text]