Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Language: English
    In: Investigational New Drugs, 2016, Vol.34(5), pp.584-595
    Description: Background MET is a tyrosine kinase receptor involved in the regulation of cell proliferation and migration. Reported here are the phase I dose-escalation results for LY2875358, a monoclonal antibody against MET, in Japanese patients with advanced malignancies. Methods The study comprised a 3 + 3 dose-escalation part for LY2875358 monotherapy in patients with advanced malignancies (Part A) followed by an assessment of LY2875358 in combination with erlotinib or gefitinib in patients with non-small cell lung cancer (Part B). LY2875358 was administered once every 2 weeks. The primary objective was to evaluate the safety and tolerability of LY2875358; secondary objectives included evaluation of pharmacokinetics, pharmacodynamics, and antitumor activity. Results Eleven patients received LY2875358 monotherapy at 3 dose levels (700 mg, N  = 3; 1400 mg, N  = 3; 2000 mg, N  = 5) and 6 patients received LY2875358 2000 mg in combination with erlotinib ( N  = 3) or gefitinib ( N  = 3). No dose-limiting toxicities or serious adverse events related to LY2875358 were observed. The most frequently reported drug-related adverse events were hypoalbuminemia (2 patients) in Part A and dermatitis acneiform (4 patients) in Part B. LY2875358 area under the curve (AUC) and maximum concentration (C max ) increased with dose over the dose range of 700 mg to 2000 mg. A best response of stable disease was achieved by 2/11 patients in Part A and 4/6 patients in Part B (disease control rate: 35 %). Conclusions LY2875358 at doses up to 2000 mg demonstrated a favorable safety and tolerability profile as monotherapy or in combination with erlotinib or gefitinib in Japanese patients with advanced malignancies.
    Keywords: Antibodies, monoclonal ; Epidermal growth factor receptor ; LY2875358 ; MET ; Pharmacokinetics ; Solid tumors
    ISSN: 0167-6997
    E-ISSN: 1573-0646
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Investigational New Drugs, 2018, Vol.36(4), pp.536-544
    Description: Purpose Approximately 3% of lung cancer bears mutations leading to MET exon 14 skipping, an oncogenic driver which is further evidenced by case reports of patient response to MET kinase inhibitor treatment. Approximately 15% of tumors harboring MET exon14 skipping have concurrent MET amplification. Experimental Design Merestinib is a type II MET kinase inhibitor. Emibetuzumab, a bivalent anti-MET antibody, internalizes MET receptor. Each single agent and the combination were evaluated in the Hs746t gastric cancer line bearing MET exon14 skipping and MET amplification. Results Merestinib inhibited Hs746t cell proliferation (IC 50 =34 nM) and totally eliminated pMET at 100nM. Emibetuzumab showed little anti-proliferative activity against Hs746t cells (IC 50 〉100nM), did not reduce pMET, and slightly reduced cell surface MET. In the Hs746t xenograft model, dose dependent differences in durability of response were seen with merestinib including durable tumor regression (91.8%) at 12 mg/kg qd. Emibetuzumab treatment (10mg/kg qw) provided transient tumor regression (37.7%), but tumors re-grew while on treatment. Concurrent combination of merestinib (6 mg/kg qd) and emibetuzumab resulted in 85% tumor regression, while a sequential combination (initiating merestinib first) resulted in longer duration of treatment response. Conclusions Data in this study support a clinical evaluation of merestinib in patients with MET exon 14 skipping (NCT02920996). As a type II MET kinase inhibitor, merestinib may provide a therapeutic option to treatment naïve patients or to patients who progress on type I MET inhibitor treatment. Data also support clinical evaluation of the sequential combination of merestinib with emibetuzumab when patients progress on single agent merestinib.
    Keywords: Merestinib ; Emibetuzumab ; MET exon 14 skipping ; MET kinase inhibitor ; MET antibody ; LY2801653 ; LY2875358
    ISSN: 0167-6997
    E-ISSN: 1573-0646
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Cancer Chemotherapy and Pharmacology, 2017, Vol.80(6), pp.1197-1207
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00280-017-3445-z Byline: Daisuke Sakai (1), Hyun Cheol Chung (2), Do-Youn Oh (3,4), Se Hoon Park (5), Shigenori Kadowaki (6), Yeul Hong Kim (7), Akihito Tsuji (8), Yoshito Komatsu (9), Yoon-Koo Kang (10), Kazunori Uenaka (11), Sameera R. Wijayawardana (12), Volker Wacheck (12), Xuejing Wang (12), Ayuko Yamamura (11), Toshihiko Doi (13) Keywords: Antibodies, monoclonal, humanized; Clinical trial; Phase II; LY2875358; MET protein, human; Stomach neoplasms Abstract: Purpose Mesenchymal--epithelial transition factor (MET) is expressed in gastric cancer and associated with poor clinical outcomes. We assessed activity, safety, and pharmacokinetics of emibetuzumab, a bivalent monoclonal anti-MET antibody that blocks ligand-dependent and ligand-independent MET signaling. Methods This non-randomized, single-arm, Phase 2 study enrolled Asian patients with MET diagnostic positive advanced gastric adenocarcinoma. Emibetuzumab (2000 mg, intravenous) was given on days 1 and 15 (28-day cycle). The primary endpoint was 8-week progression-free survival rate. Secondary objectives included safety, pharmacokinetics, overall survival, and change in tumor size. Results Tumors from 65 patients were immunohistochemically screened to enroll 15 MET diagnostic positive patients (23% positivity 8 Japanese, 7 Korean 10 male). Eight-week progression-free survival rate was 0.47 (70% CI, 0.33--0.59). Disease control rate was 40% (target lesion decreases, three patients no complete/partial responses according to RECIST). Median overall survival was 17.1 weeks (95% CI, 6.3--not achievable). No serious emibetuzumab-related adverse events or new safety signals emerged. GradeAaAaAeAc[yen]3 possibly drug-related adverse events were hyperkalemi hyponatremia, and hyperuricemia (one each). Emibetuzumab's pharmacokinetics profile was similar to that observed previously. MET expression and clinical outcomes were not obviously associated. Conclusion Emibetuzumab was well tolerated with limited single-agent activity in advanced gastric adenocarcinoma. Author Affiliation: (1) Osaka University Hospital, Osaka, 565-0871, Japan (2) Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 03722, South Korea (3) Seoul National University Hospital, Seoul, 03080, South Korea (4) Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, South Korea (5) Sungkyunkwan University Samsung Medical Center, Seoul, 06351, South Korea (6) Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan (7) Korea University College of Medicine, Seoul, 02841, South Korea (8) Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kita, 761-0793, Japan (9) Cancer Center, Hokkaido University Hospital, Sapporo, 060-8648, Japan (10) Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, South Korea (11) Eli Lilly Japan K.K., Kobe, 651-0086, Japan (12) Eli Lilly and Company, Indianapolis, IN, 46285, USA (13) National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa, Chiba, 277-8577, Japan Article History: Registration Date: 23/09/2017 Received Date: 05/09/2017 Accepted Date: 22/09/2017 Online Date: 25/10/2017
    Keywords: Antibodies, monoclonal, humanized ; Clinical trial ; Phase II ; LY2875358 ; MET protein, human ; Stomach neoplasms
    ISSN: 0344-5704
    E-ISSN: 1432-0843
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages