Phase IB study of the EpCAM antibody adecatumumab combined with docetaxel in patients with EpCAM-positive relapsed or refractory advanced-stage breast cancer

1区 · 医学

Article

作者: Schlimok, G ; Schmidt, M ; Baeuerle, P A ; Marschner, N ; Eiermann, W ; Lang, A ; Schuler, M ; Göppel, G ; Wolf, A ; Wolf, C ; Rüttinger, D ; Steger, G G ; Hanusch, C A ; Sebastian, M ; Oruzio, D

BACKGROUNDTargeted therapy options in HER2-negative breast cancer are limited. This open-label, multicenter phase IB dose-escalation trial was conducted to determine safety, tolerability, and antitumor activity of a combination of docetaxel (Taxotere) and increasing doses of adecatumumab, a human IgG1 antibody targeting epithelial cell adhesion molecule (EpCAM), in EpCAM-positive relapsed or primary refractory advanced-stage breast cancer.PATIENTS AND METHODSPatients pretreated with up to four prior chemotherapy regimens received increasing adecatumumab doses either every 3 weeks (q3w) or weekly (qw) combined with docetaxel (100 mg/m² q3w). Primary end points were safety and tolerability. Antitumor activity was evaluated according to RECIST. Clinical benefit was defined as complete or partial response or stable disease for ≥24 weeks.RESULTSThirty-one evaluable patients were treated. Most adverse events were mild to moderate in severity. Neutropenia, leukocytopenia, lymphopenia, and diarrhea (dose-limiting) were the most frequent toxic effects. Maximum tolerated doses of adecatumumab given in combination with docetaxel were 550 mg/m² q3w and 360 mg/m² qw. Clinical benefit was observed in 44% of patients treated with q3w adecatumumab and docetaxel, increasing to 63% in patients with high EpCAM-expressing tumors.CONCLUSIONCombination therapy of adecatumumab and docetaxel is safe, feasible, and potentially active in heavily pretreated advanced-stage breast cancer.

2012-05-20·Journal of Clinical Oncology

Effect of anti-CD19 BiTE blinatumomab on complete remission rate and overall survival in adult patients with relapsed/refractory B-precursor ALL.

作者: Reichle, Albrecht ; Klappers, Petra ; Marks, Reinhard ; Ritgen, Matthias ; Zugmaier, Gerhard ; Hoelzer, Dieter ; Topp, Max ; Einsele, Hermann ; Mergen, Noemi ; Stelljes, Matthias ; Neumann, Svenja ; Goekbuget, Nicola ; Goebeler, Marie-Elisabeth ; Monika, Brueggemann ; Horst, Heinz-August ; Viardot, Andreas ; Bargou, Ralph

6500^ Background: Blinatumomab is a bispecific T-cell engaging (BiTE) antibody that directs cytotoxic T-cells to CD19 expressing target cells. Methods: In adult patients with relapsed/refractory B-precursor ALL, a phase II dose ranging trial is being conducted to evaluate efficacy and safety of blinatumomab. The primary endpoint is the rate of hematological complete remission (CR) or CR with partial hematological recovery (CRh*) within 2 cycles of blinatumomab treatment. Blinatumomab is administered by continuous intravenous infusion for 28-days followed by a 14-day treatment-free interval. Responding patients can receive 3 additional cycles of treatment or proceed to bone marrow transplantation. Three dose levels were explored as shown in the table. Results: In total 36 patients have been enrolled, 25 are currently evaluable. Seventeen out of 25 treated patients (68%) reached a hematological CR/CRh* and a minimal residual disease (MRD) response (MRD level <10-4) within the first 2 cycles. Five out of 17 responders (29%) showed a CRh* due to partial recovery of platelets. For the first 18 patients, response duration is 7.1 months and the median follow-up time for overall survival (OS) is 9.7 months (median not reached). Six cases of relapses have been recorded of which 3 were CD19+, and 3 CD19-. As final dose 5 µg/m²/day in week 1 and 15 µg/m²/day for the remaining treatment (cohort 2a and 3) was selected. In these cohorts (n=12), the most common treatment emergent adverse events (TEAEs, all grade 1-2) were pyrexia (67%), headache (33%) and tremor (33%). TEAEs of grade ≥3 (7 in 5 patients, no grade 4), irrespective of relationship, were infections, confusion, epilepsy, hypertension and thrombocytopenia. Conclusions: The final dose was well-tolerated and produced an exceptionally high complete remission rate. A global phase 2 study to confirm these data is underway. [Table: see text]

2012-04-15·Cancer Research

Abstract 3524: A novel approach to targeting mutated colorectal adenocarcinomas with T cell-engaging CEA/CD3-bispecific BiTE investigational antibody MEDI-565

作者: Hammond, Scott A. ; Coats, Steven ; Cheng, Lily ; Oberst, Michael D. ; Baeuerle, Patrick A. ; Lutterbuese, Petra ; Mulgrew, Kathy ; Amman, Maria ; Richman, Laura ; Fuhrmann, Stacy

AbstractColorectal cancer (CRC) cells can harbor somatic mutations with strong impact on cancer cell signaling that limit the effectiveness of both chemotherapy and targeted therapies including monoclonal antibodies and kinase inhibitors. Therefore, novel therapeutic modalities are needed that are not impacted by the presence of such genetic mutations. We have here evaluated a CEA/ CD3-bispecific BiTE antibody termed MEDI-565 (also known as MT111) for its ability to redirect cytotoxic T cells for lysis in co-cultures and in xenograft models of human CRC lines harboring oncogenic mutations. Redirected lysis of CEA-positive tumor cells by MEDI-565 occurred in a manner dependent on CEA surface antigen density but independent of exogenously added soluble CEA. Importantly, the potency of lysis was independent of the mutational status of genes commonly mutated or lost in colorectal and other cancers, including frequent mutations in KRAS, BRAF, PI3KCA, PTEN and TP53 genes. In mouse xenograft models, the ability of MEDI-565 to inhibit tumor growth was likewise independent of the mutational status of the human tumor xenograft models. Our findings suggest that MEDI-565 warrants further clinical investigation as a potential treatment option for patients with CEA-positive tumors harboring somatic mutations that are less responsive to traditional chemotherapy or targeted agents.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3524. doi:1538-7445.AM2012-3524

100 项与 Micromet, Inc. 相关的药物交易

登录后查看更多信息

100 项与 Micromet, Inc. 相关的转化医学

登录后查看更多信息