Stephen Michael Kelsey
Hoffmann-La Roche
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Featured researches published by Stephen Michael Kelsey.
Journal of Clinical Oncology | 2005
David B. Agus; Michael S. Gordon; Charles E. Taylor; Ronald B. Natale; Beth Y. Karlan; David S. Mendelson; Michael F. Press; David Edward Allison; Mark X. Sliwkowski; Gracie Lieberman; Stephen Michael Kelsey; Gwen Fyfe
PURPOSE Pertuzumab, a recombinant humanized monoclonal antibody (2C4), binds to extracellular domain II of the HER-2 receptor and blocks its ability to dimerize with other HER receptors. Pertuzumab represents a new class of targeted therapeutics known as HER dimerization inhibitors. A clinical study was conducted to investigate safety and pharmacokinetics of pertuzumab and to perform a preliminary assessment of HER dimerization inhibition as a treatment strategy. PATIENTS AND METHODS Patients with incurable, locally advanced, recurrent or metastatic solid tumors that had progressed during or after standard therapy were recruited to a dose-escalation study of pertuzumab (0.5 to 15 mg/kg) given intravenously every 3 weeks. RESULTS Twenty-one patients received pertuzumab and 19 completed at least two cycles. Pertuzumab was well tolerated. Overall, 365 adverse events were reported and 122 considered to be possibly drug related. Of these, 116 were of grade 1 to 2 intensity. The pharmacokinetics of pertuzumab were similar to other humanized immunoglobulin G antibodies, supporting a 3-week dosing regimen. Trough plasma concentrations were in excess of target concentrations at doses greater than 5 mg/kg. Two patients, one with ovarian cancer (5.0 mg/kg) and one with pancreatic islet cell carcinoma (15.0 mg/kg), achieved a partial response. Responses were documented by Response Evaluation Criteria in Solid Tumors after 1.5 and 6 months of pertuzumab therapy, and lasted for 11 and 10 months, respectively. Stable disease lasting for more than 2.5 months (range, 2.6 to 5.5 months) was observed in six patients. CONCLUSION These results demonstrate that pertuzumab is well tolerated, has a pharmacokinetic profile which supports 3-week dosing, and is clinically active, suggesting that inhibition of dimerization may be an effective anticancer strategy.
Journal of Clinical Oncology | 2010
Sharmila Makhija; Lukas Amler; Dana Glenn; Frederick R. Ueland; Michael A. Gold; Don S. Dizon; Virginia E. Paton; Chin Yu Lin; Thomas Januario; Kimmie Ng; Andreas Strauss; Stephen Michael Kelsey; Mark X. Sliwkowski; Ursula A. Matulonis
PURPOSE Pertuzumab is a humanized monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization and has single-agent activity in recurrent epithelial ovarian cancer. The primary objective of this phase II study was to characterize the safety and estimate progression-free survival (PFS) of pertuzumab with gemcitabine in patients with platinum-resistant ovarian cancer. PATIENTS AND METHODS Patients with advanced, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received a maximum of one prior treatment for recurrent cancer were randomly assigned to gemcitabine plus either pertuzumab or placebo. Collection of archival tissue was mandatory to permit exploration of biomarkers that would predict benefit from pertuzumab in this setting. RESULTS One hundred thirty patients (65 per arm) were treated. Baseline characteristics were similar between arms. The adjusted hazard ratio (HR) for PFS was 0.66 (95% CI, 0.43 to 1.03; P = .07) in favor of gemcitabine + pertuzumab. The objective response rate was 13.8% in patients who received gemcitabine + pertuzumab compared with 4.6% in patients who received gemcitabine + placebo. In patients whose tumors had low HER3 mRNA expression (< median, n = 61), an increased treatment benefit was observed in the gemcitabine + pertuzumab arm compared with the gemcitabine alone arm (PFS HR = 0.32; 95% CI, 0.17 to 0.59; P = .0002). Grade 3 to 4 neutropenia, diarrhea, and back pain were increased in patients treated with gemcitabine + pertuzumab. Symptomatic congestive heart failure was reported in one patient in the gemcitabine + pertuzumab arm. CONCLUSION Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. Low HER3 mRNA expression may predict pertuzumab clinical benefit and be a valuable prognostic marker.
Archive | 2003
Birgit Bossenmaier; Hans-Joachim Müller; Hans Koll; Mark X. Sliwkowski; Stephen Michael Kelsey
Archive | 2003
Hans Koll; Birgit Bossenmaier; Hans-Joachim Müller; Mark X. Sliwkowski; Stephen Michael Kelsey
Archive | 2012
Hans Koll; Birgit Bossenmaier; Hans-Joachim Müller; Mark X. Sliwkowski; Stephen Michael Kelsey
Archive | 2012
Hans Koll; ハンス コル; Birgit Bossenmaier; ビルギット ボッセンマイヤー; Hans-Joachim Dr Mueller; ハンス−ヨアヒム、ミュラー; Mark X. Sliwkowski; マーク エックス. スリウコウスキー,; Stephen Michael Kelsey; ステファン マイケル ケルシー
Archive | 2006
Mark X. Sliwkowski; Stephen Michael Kelsey
Archive | 2003
Hans Koll; Birgit Bossenmaier; Hans-Joachim Müller; Mark X. Sliwkowski; Stephen Michael Kelsey
Archive | 2003
Hans Koll; Birgit Bossenmaier; Hans-Joachim Müller; Mark X. Sliwkowski; Stephen Michael Kelsey
Archive | 2003
Birgit Bossenmaier; Stephen Michael Kelsey; Hans Koll; Hans-Joachim Müller; Mark X. Sliwkowski