In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 3104-3104
Kurzfassung:
3104 Background: It has been demonstrated in vivo that HGF-MET signaling axis is a key molecular determinant in tumor invasion and there is a significant association in HGF expression and mesenchymal phenotype in addition to immune cell recruitment. We have developed a HGF neutralizing humanized monoclonal antibody antibody, YYB-101. The aim of this study was to determine the maximum tolerate dose (MTD), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of YYB101, in patients with refractory solid tumors. Methods: YYB101 was administered intravenously at once every 2 weeks doses of 0.3, 1, 3, 5, 10, 20, 30 mg/kg, according to a 3+3 dose escalation design. Enrolled patients were planned to receive YYB101 until disease progression or intolerable toxicity. The escalation and expansion cohorts (20mg/kg) were completed. Pre-planned biomarker analysis was performed in parallel. Results: 39 heavily pre-treated refractory cancer patients were enrolled and received YYB101. No DLT was observed. YYB101 demonstrated dose proportional PK up to the dose of 30 mg/kg. No patients discontinued treatment because of adverse events. Based on PK analysis and toxicity data, the recommended dose was determined as 20 mg/kg. Of 39 evaluation patients, there was 1 confirmed partial response for 〉 +14months (2.5%, N = 1; 1 (of 2) sebaceous carcinoma) and 17 stable disease as best response (43.5%, N = 17; 7 (of 13) CRC, 3 (of 4) melanoma, 1 (of 2) sebaceous carcinoma, 1 (of 3) gastric, 1 (of 1) basal cell carcinoma, 2 (of 10) ovarian cancer, 1 (of 1) HCC, 1 (of 1) lung cancer). Of note, 1 sebaceous carcinoma patient who have failed to ≥2+ lines of chemotherapy, have been responding to YYB for 14 months. The MET and HGF expressions by immunohistochemistry (IHC) were evaluated in 19 and 17 tumor specimens, respectively. Neither protein expressions were significant predictors for treatment response to anti-HGF antibody. However, we have observed significant reduction in HGF in responders to YYB. Two long-term responders had mesenchymal signature in RNA sequencing. Conclusions: YYB101 has a favorable safety profile in patients with refractory solid tumors and a dose-proportional PK. Efficacy data are encouraging and phase II combination therapy with YYB101 is planned to be open in metastatic CRC patients as salvage treatment. The predictive power of mesenchymal signature in YYB responders will be defined prospectively. Clinical trial information: 02499224.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.15_suppl.3104
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2019
ZDB Id:
2005181-5
