Vorolanib (Cm082) In Chinese Patients With Advanced Solid Tumor: A Phase 1, Open-Label, Dose Escalation Study.

2580 Background: Vorolanib (CM082) is a potent and selective inhibitor of VEGFR and PDGFR, which is well tolerated from 20 to 400 mg without G3/4 treatment-related AEs (TRAEs) in patients in US. Here we present a phase I dose escalation study that assessed vorolanib in Chinese patients with advanced solid tumor. Methods: Patients with advanced solid tumors were enrolled to receive escalating dose of vorolanib once daily from 50 mg to 300 mg following the 3+3 design. Primary endpoints included evaluation of safety, pharmacokinetics, and maximum-tolerated dose (MTD) determination. Results: 19 patients were enrolled and treated, including 12 RCC. Most patients (n = 18) have received at least one prior systemic treatments, in which 10 have been treated with VEGFR TKIs. No DLT was seen, the MTD was not achieved. The most common TRAEs were leukopenia (9/19), fatigue (9/19), diarrhea (8/19), neutropenia (8/19), and hypertension (8/19). G3 or higher events were seen in 7 patients across 100 to 250 mg dose cohort. PK analysis was shown in table 1. Partial response was seen in 1 RCC patients in the 200 mg cohort, and 11 stable disease were seen in all dose cohorts. Conclusions: Vorolanib has an acceptable safety profile and showed preliminary activities in RCC. An expansion of RCC-enriched cohort is ongoing. Clinical trial information: NCT01863485.PK parameters. 50 mg (n = 4) 100 mg (n = 3) 150 mg (n = 3) 200 mg (n = 3) 250 mg (n = 4) Single dose t1/2 hr 3.95 ± 0.56 8.01 ± 1.67 5.78 ± 0.53 5.25 ± 0.40 6.20 ± 1.82 Tmax hr 4.00 2.33 ± 0.58 2.67 ± 0.58 3.67 ± 0.58 2.75 ± 0.96 Cmax ng/mL 239.82 ± 39.24 566.86 ± 253.54 727.75 ± 133.36 857.22 ± 94.49 1003.79 ± 92.73 AUC(0-48 h) hr*ng/mL 1973.24 ± 435.85 5501.26 ± 2972.74 6327.04 ± 654.03 7689.95 ± 1684.58 8435.56 ± 1515.97 AUC (0-inf) hr*ng/mL 1981.85 ± 437.81 5586.84 ± 3011.58 6352.55 ± 669.81 7706.55 ± 1688.32 8481.12 ± 1539.81 Multiple doses t1/2 hr 4.28 ± 0.75 5.03 ± 1.69 6.25 ± 0.81 4.83 ± 0.14 4.46 ± 0.78 Tmax hr 4.00 ± 1.63 2.33 ± 0.58 3.00 ± 1.00 3.00 ± 1.00 2.75 ± 0.05 Cmax ng/mL 254.19 ± 94.23 649.98 ± 147.51 923.83 ± 208.44 811.55 ± 266.45 959.62 ± 431.12 AUC (0-24 h) hr*ng/mL 2168.81 ± 874.37 5910.91 ± 1909.47 9224.53 ± 3153.11 6579.73 ± 2264.7 6968.75 ± 3265.82 AUC (0-inf) hr*ng/mL 2235.38 ± 883.95 6283.97 ± 2337.41 10068.74 ± 3487.21 6823.74 ± 2345.54 7221.1 ± 3439.7