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Hab da mal ein paar Sachen gesammelt: Hier will GPC klinische Daten vorstellen: Annual Meeting
The American Society of Hematology
48th Annual Meeting and Exposition
Meeting Dates: December 9-12, 2006 Exposition Dates: December 9-11, 2006
Friday Satellite Symposia: December 8, 2006
Orange County Convention Center
Orlando, Florida
Each December, the Society's annual meeting provides hematologists from around the world a forum for discussing critical issues in hematology. Nearly 20,000 clinicians, scientists, and others attend the four-day meeting, which consists of a superb educational program and cutting-edge scientific sessions. Oral and poster presentations, which are chosen by peer-reviewers from abstracts submitted prior to the annual meeting, are featured at the annual meeting and contain the latest and most exciting developments in scientific research. Plenary symposia and named lectures on specialized areas of hematology are also presented throughout the meeting program.
During the annual meeting, attendees can also visit the state-of-the-art exposition, which features exhibits from pharmaceutical companies, medical suppliers, clinical diagnostic and research-based companies, publishers, and non-profit organizations.
xxxxxxxxxxxxx Two Phase I Open-Label Studies of the Fully Human HLA-DR-Specific IgG4 Monoclonal Antibody 1D09C3 in Patients with Relapsed and/or Refractory B-Cell Lymphoproliferative Neoplasias on a Weekly and Bi-Weekly Dosing Scheme. Session Type: Poster Session, Board #908-II
Alessandro M. Gianni, Carmelo Carlo-Stella, Anna Guidetti, Michael Hallek, Carmen Schweighofer, Clemens Wendtner, Michele Ghielmini, Erica Lerch, Sabine Sperka, Douglas Greene, Oliver Krieter, Faith Nathan, Michael Petrone Medical Oncology, Istituto Nazionale Tumori, Milan, Italy; Medical Clinic I, University of Cologne, Cologne, Germany; Medical Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; GPC Biotech AG, Munich, Germany; GPC Biotech Inc, Princeton, NJ, USA
Background: Lymphomas are increasing in frequency and represent the fifth most common cancer diagnosis in the United States. 1D09C3 is a fully human anti-HLA-DR monoclonal antibody (mAb) derived from a human combinatorial antibody library (HuCAL) that has consistently demonstrated activity against various lymphoid tumors, both in vitro and in vivo (Nat Med 2002;8:801-7). Therefore 1D09C3 may offer a novel therapy to patients with B-cell lymphoma who have failed therapy. Two phase I studies are ongoing to determine i) the maximum tolerated dose (MTD) and phase II recommended dose (RD), ii) the pharmacodynamic (pd)- and pharmacokinetic (pk)-profile and iii) the immunogenicity of 1D09C3 given within a bi-weekly and weekly schedule in this patient population.
Material and methods: Patients with relapsed/refractory B-cell lymphoproliferative diseases are included in the two studies. 1D09C3 dose escalation is performed using modified Fibonacci increments with a minimum of 3 patients (pts) per dose level. It is administered once every week or every other week by a 2-hour intravenous (iv) infusion at escalating dose levels of 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 and 10 mg/kg/day for either 4 or 8 weeks. All toxicities are assessed according to the NCI CTC version 3.0. Blood samples are collected at different times in the study to determine pd- and pk- parameters and to assess immunogenicity of 1D09C3.
Results: 19 pts have been enrolled into both protocols to date (13M/6F), median age 58 (range 30-76), pts with Hodgkins lymphoma (5), non-Hodgkins lymphoma (8) and chronic lymphocytic leukemia (6). The 4th dose level (2.0mg/kg/day) has been completed within the bi-weekly dosing scheme and accrual is ongoing until the MTD and thus the phase II RD will be determined. The safety profile was positive, with only few and mild treatment-related side-effects such as fatigue noted, although one dose limiting toxicity (DLT) was seen at the bi-weekly dose level 0.5 mg/kg/day.
Pk analysis of intravenous 1D09C3 indicated the drug to be cleared rapidly from blood circulation. 2 pts have been tested positive for human anti-1D09C3 antibodies (HAHA) at the 2nd and 3rd dose level, respectively; no allergic reactions were noticed. Clinical benefit was observed in 3 out of 14 evaluable pts who experienced partial response (PR), whereas 8 had no changes (NC) and 3 progressive disease (PD). After study completion an independent response evaluation team (RET) will review the information provided and determine individual treatment responses for the overall study.
Conclusion: Two phase I dose escalation studies of the anti-HLA-DR mAb 1D09C3 are currently open in three sites for accrual of pts with relapsed/refractory B-cell lymphoproliferative diseases to determine the MTD and phase II RD for a weekly and bi-weekly schedule. Preliminary data suggest that 1D09C3 is well tolerated within this heavily pre-treated patient population. Pd- and pk-data, development of HAHA and clinical responses will continue to be evaluated.
Abstract #2730 appears in Blood, Volume 108, issue 11, November 16, 2006
Keywords: Phase I|Monoclonal antibody|Lymphoproliferative disorder
Sunday, December 10, 2006 9:00 AM
Poster Session: Novel and Targeted Therapy of Non-Hodgkin Disease (NHL) (9:00 AM-8:00 PM xxxxxxxxxxxxxxxxxxxxxxx ville hat noch nachgehakt wegen HAHA-Reaktionen bei einigen Patienten:
Antworten bezüglich der HAHA Reaktionen von Frau GL/MOR und Herrn Brändle/GPC. Von mir inhaltlich zusammen gefasst, damit hier nicht der Originaltext gepostet werden muss (hiergegen hat so manche IR etwas):
Für Frau Gutjahr-Löser ist eine HAHA-Reaktion nicht überraschend und ungewöhnlich. Auch bei anderen, voll humanen Antikörpern wie z. B. Humira, oder auch bei anderen "Biologicals", wie z. B. Insulin, EPO oder Faktor 8, würden Antikörper gegen diese menschlichen Proteine beobachtet. Gründe hierfür sind nicht klar und könnten z.b. sein: Art der Verabreichung, "Reinheit", Formulierung oder Glycolysierung.
Für Herrn Brändle ist die Aussage, dass keine allergischen Reaktionen zu beobachten waren die wichtigste Aussage, die eine Frage zu der Reaktion schon beantworte. Auch er sieht in der HAHA Reaktion nichts ungewöhnliches. Auch bei vollständig humanen AK würden AK gegen diese fremden Proteine gebildet werden können. Es sei völlig normal. Bei Humira, einem vollständig humanen AK von Astra Zeneka seien bei 15% der Patienten HAHA-Reaktionen festgestellt worden. Mögliche Gründe: natürliche Varianz von Patient zu Patient oder Heterogenität im Herstellungsprozess. Kritisch wäre es erst, wenn eine allergische Reaktion ausgelöst würde. Insgesamt bezeichnet Herr Brändle die Daten sehr ermutigend und das Sicherheitsprofil als sehr gut. Zudem seien erste Anzeichen der Wirksamkeit sehr erfreulich. Vor allem wenn man bedenkt dass die Dosierungen noch sehr niedrig waren und dadurch die Sättigung der Rezeptoren mit diesem AK noch gar nicht gegeben war.
(Humane antihumane Antikörper = HAHA )
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx Das hört sich als Zwischenstand der P1 sehr gut an! Ab Sommer oder 2. HJ 2007 geht das in P2!
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