A phase I study to evaluate the safety, tolerability, and pharmacokinetics of MSB0254 in Chinese patients with solid tumors

3023 Background: MSB0254 is a humanized vascular endothelial growth factor receptor 2 (VEGFR-2) monoclonal antibody. MSB0254 inhibits angiogenesis induced by either VEGF-A or –C. This trial is a phase I study to evaluate MSB0254’s safety, tolerability and PK profiles, as well as early anti-cancer activities in Chinese patients with advanced solid tumors. Methods: In this phase I study (NCT04381325), locally advanced or metastatic solid tumor patients failed previous standard treatments were enrolled. In the dose escalation phase, following 3+3 rules, MSB0254 was given intravenously Q2W (every 2 weeks) at 4mg/kg, 8mg/kg, 12mg/kg, 16mg/kg, and Q3W at 20mg/kg. In the dose expansion phase, patients with selected tumor types will be treated with MSB0254 at 16mg/kg Q2W or 20mg/kg Q3W. Primary objectives were to evaluate the safety and tolerability and to identify maximum tolerable dose (MTD) and/or Recommended Phase 2 Dose (RP2D). Secondary objectives included the assessment of pharmacokinetics, immunogenicity, and preliminary efficacy per RECIST1.1. Results: As of 10th Jan, 2022, a total of 22 Chinese patients have been enrolled into the dose escalation phase and treated with MSB0254 at different dose levels from 4-16mg/kg Q2W or 20mg/kg Q3W. MTD was not reached. One DLT was reported in 12mg/kg Q2W dose cohort. A subject with intra-cholangial carcinoma developed G3 (grade 3) upper gastrointestinal hemorrhage on the C1D13. The adverse event was resolved after symptomatic treatment. The most common treatment-emergent adverse events (TEAEs) (>10%) included: hypertension (27.3%), AST increased (27.3%), γ-GGT increased (22.7%), neutrophil count decreased (18.2%), proteinuria (18.2%), WBC count decreased (13.6%), platelet count decreased (13.6%) and anemia (13.6%). Three subjects (13.6%) experienced G3 TEAEs: 1 upper gastrointestinal hemorrhage, 1 anemia and 1 Hypertriglyceridemia. No G4/5 TEAE was observed. And three subjects (13.6%) experienced 3 SAEs: 1 upper gastrointestinal hemorrhage, 1 G2 intestinal obstruction caused hospitalization and 1 G2 fatigue caused hospitalization. MSB0254 displayed a dose proportional pharmacokinetic profile between 4-16 mg/kg Q2W with calculated T1/2 of 6-9 days. Eighteen subjects had at least one tumor assessment per RECIST 1.1 after MSB0254 treatment. Eleven subjects (61.1%) had best response of stable disease (SD). Four of them had stable disease for more than 6 months, including a neuroendocrine tumor (NET), a gastric cancer, an epithelioid hemangioendothelioma (EHE) and a submaxillary gland carcinoma patient. Conclusions: MSB0254 demonstrated a manageable safety profile and preliminary antitumor activity in patients with advanced solid tumors. 16mk/kg Q2W is recommended as RP2D. 20mg/kg Q3W is still under investigation. The study of MSB0254 on the expansion phase in selected tumor patients is ongoing. Clinical trial information: NCT04381325.