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Horst Lindhofer - One of the best experts on this subject based on the ideXlab platform.

  • with
    2016
    Co-Authors: Marion G. Ott, Michael Hennig, Horst Lindhofer, Rolf Linke, Gerhard Moldenhauer, Rolf Spannagl, Mirko M. Essing, Diane Seimetz
    Abstract:

    Humoral response to Catumaxomab correlates with clinica

  • The Role of Relative Lymphocyte Count as a Biomarker for the Effect of Catumaxomab on Survival in Malignant Ascites Patients: Results from a Phase II/III Study
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2014
    Co-Authors: Markus M. Heiss, Carsten Bokemeyer, Michael A. Ströhlein, D. Arnold, Simon L. Parsons, D. Seimetz, Horst Lindhofer, Elisabeth Schulze, Michael Hennig
    Abstract:

    Purpose: We report the role of relative lymphocyte count (RLC) as a potential biomarker with prognostic impact for Catumaxomab efficacy and overall survival (OS) based on a post hoc analysis of the pivotal phase II/III study of intraperitoneal Catumaxomab treatment of malignant ascites. Experimental Design: The impact of treatment and RLC on OS was evaluated using multivariate Cox models. Kaplan–Meier and log-rank tests were used for group comparisons. Survival analyses were performed on the safety population [patients with paracentesis plus ≥1 dose of Catumaxomab ( n = 157) and paracentesis alone ( n = 88)]. Determination of the optimal cutoff value for RLC was based on five optimality criteria. Results: OS was significantly longer with Catumaxomab versus paracentesis alone ( P = 0.0219). The 6-month OS rate with Catumaxomab was 28.9% versus 6.7% with paracentesis alone. RLC had a positive impact on OS and was an independent prognostic factor ( P 13% ( n = 159: Catumaxomab, 100 and control, 59), Catumaxomab was associated with a favorable effect on OS versus paracentesis alone ( P = 0.0072), with a median/mean OS benefit of 41/131 days and an increased 6-month survival rate of 37.0% versus 5.2%, respectively. In patients with RLC ≤ 13% at screening ( n = 74: Catumaxomab, 50 and control, 24), the median (mean) OS difference between the Catumaxomab and the control group was 3 (16) days, respectively ( P = 0.2561). Conclusions: OS was significantly improved after Catumaxomab treatment in patients with malignant ascites. An RLC > 13% at baseline was a significant prognostic biomarker. Clin Cancer Res; 20(12); 3348–57. ©2014 AACR .

  • Humoral response to Catumaxomab correlates with clinical outcome: Results of the pivotal phase II/III study in patients with malignant ascites
    International journal of cancer, 2011
    Co-Authors: Marion G. Ott, Michael Hennig, Horst Lindhofer, Rolf Linke, Frederik Marmé, Gerhard Moldenhauer, Rolf Spannagl, Mirko M. Essing, D. Seimetz
    Abstract:

    The trifunctional antibody Catumaxomab is a targeted immunotherapy for the intraperitoneal treatment of malignant ascites. In a Phase II/III trial in cancer patients (n = 258) with malignant ascites, Catumaxomab showed a clear clinical benefit vs. paracentesis and had an acceptable safety profile. Human antimouse antibodies (HAMAs), which could be associated with beneficial humoral effects and prolonged survival, may develop against Catumaxomab as it is a mouse/rat antibody. This post hoc analysis investigated whether there was a correlation between the detection of HAMAs 8 days after the fourth Catumaxomab infusion and clinical outcome. HAMA-positive and HAMA-negative patients in the Catumaxomab group and patients in the control group were analyzed separately for all three clinical outcome measures (puncture-free survival, time to next puncture and overall survival) and compared to each other. There was a strong correlation between humoral response and clinical outcome: patients who developed HAMAs after Catumaxomab showed significant improvement in all three clinical outcome measures vs. HAMA-negative patients. In the overall population in HAMA-positive vs. HAMA-negative patients, median puncture-free survival was 64 vs. 27 days (p < 0.0001; HR 0.330), median time to next therapeutic puncture was 104 vs. 46 days (p = 0.0002; HR 0.307) and median overall survival was 129 vs. 64 days (p = 0.0003; HR 0.433). Similar differences between HAMA-positive and HAMA-negative patients were seen in the ovarian, nonovarian and gastric cancer subgroups. In conclusion, HAMA development may be a biomarker for Catumaxomab response and patients who developed HAMAs sooner derived greater benefit from Catumaxomab treatment.

  • Effect of Catumaxomab on EpCAM+ tumor cells in vitro in the presence of immune effector cells from ovarian cancer patients treated with chemotherapy.
    Journal of Clinical Oncology, 2011
    Co-Authors: Klaus Pietzner, Jalid Sehouli, D. Seimetz, Horst Lindhofer, Holger Martinius, J Atz, K. Dettmar, R. Spannagl, P. Schroeder, G. Oskay-Özcelik
    Abstract:

    e13043 Background: The trifunctional antibody Catumaxomab (anti-EpCAM x anti-CD3) is approved in the EU for the intraperitoneal treatment of malignant ascites. Since chemotherapy may impair the fun...

  • Humoral tumor-associated immune responses induced by Catumaxomab in patients with malignant ascites.
    Journal of Clinical Oncology, 2011
    Co-Authors: Peter Ruf, Michael Jäger, D. Seimetz, H. Martinius, B. Foerster, Horst Lindhofer
    Abstract:

    2575 Background: Catumaxomab is the first EU approved bispecific (anti-EpCAM x anti-CD3) trifunctional antibody for the intraperitoneal (ip) treatment of malignant ascites (MA) in patients (pts) wi...

M. M. Heiss - One of the best experts on this subject based on the ideXlab platform.

Carsten Bokemeyer - One of the best experts on this subject based on the ideXlab platform.

  • Catumaxomab with and without prednisolone premedication for the treatment of malignant ascites due to epithelial cancer: Results of the randomised phase IIIb CASIMAS study
    Medical oncology (Northwood London England), 2014
    Co-Authors: Jalid Sehouli, Klaus Pietzner, Pauline Wimberger, Ignace Vergote, Per Rosenberg, Andreas Schneeweiss, Carsten Bokemeyer, Christoph Salat, Giovanni Scambia, Dominique Berton-rigaud
    Abstract:

    This two-arm, randomised, multicentre, open-label, phase IIIb study investigated the safety and efficacy of a 3-h Catumaxomab infusion with/without prednisolone premedication to reduce Catumaxomab-related adverse events. Patients with malignant ascites due to epithelial cancer received four 3-h intraperitoneal Catumaxomab infusions with/without intravenous prednisolone (25 mg) premedication before each infusion. The primary safety endpoint was a composite safety score calculated from the incidence and intensity of the most frequent Catumaxomab-related adverse events (pyrexia, nausea, vomiting and abdominal pain). Puncture-free survival (PuFS) was a co-primary endpoint. Time to next puncture (TTPu) and overall survival (OS) were secondary endpoints. Prednisolone premedication did not result in a significant reduction in the main Catumaxomab-related adverse events. The mean composite safety score was comparable in both arms (Catumaxomab plus prednisolone, 4.1; Catumaxomab, 3.8; p = 0.383). Median PuFS (30 vs. 37 days) and TTPu (78 vs. 102 days) were shorter in the Catumaxomab plus prednisolone arm than in the Catumaxomab arm, but the differences were not statistically significant (p = 0.402 and 0.599, respectively). Median OS was longer in the Catumaxomab plus prednisolone arm than in the Catumaxomab arm (124 vs. 86 days), but the difference was not statistically significant (p = 0.186). The superiority of Catumaxomab plus prednisolone versus Catumaxomab alone could not be proven for the primary endpoint. Prednisolone did not result in a significant reduction in the main Catumaxomab-related adverse events. The study confirms the safety and efficacy of Catumaxomab administered as four 3-h intraperitoneal infusions for the treatment of malignant ascites.

  • The Role of Relative Lymphocyte Count as a Biomarker for the Effect of Catumaxomab on Survival in Malignant Ascites Patients: Results from a Phase II/III Study
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2014
    Co-Authors: Markus M. Heiss, Carsten Bokemeyer, Michael A. Ströhlein, D. Arnold, Simon L. Parsons, D. Seimetz, Horst Lindhofer, Elisabeth Schulze, Michael Hennig
    Abstract:

    Purpose: We report the role of relative lymphocyte count (RLC) as a potential biomarker with prognostic impact for Catumaxomab efficacy and overall survival (OS) based on a post hoc analysis of the pivotal phase II/III study of intraperitoneal Catumaxomab treatment of malignant ascites. Experimental Design: The impact of treatment and RLC on OS was evaluated using multivariate Cox models. Kaplan–Meier and log-rank tests were used for group comparisons. Survival analyses were performed on the safety population [patients with paracentesis plus ≥1 dose of Catumaxomab ( n = 157) and paracentesis alone ( n = 88)]. Determination of the optimal cutoff value for RLC was based on five optimality criteria. Results: OS was significantly longer with Catumaxomab versus paracentesis alone ( P = 0.0219). The 6-month OS rate with Catumaxomab was 28.9% versus 6.7% with paracentesis alone. RLC had a positive impact on OS and was an independent prognostic factor ( P 13% ( n = 159: Catumaxomab, 100 and control, 59), Catumaxomab was associated with a favorable effect on OS versus paracentesis alone ( P = 0.0072), with a median/mean OS benefit of 41/131 days and an increased 6-month survival rate of 37.0% versus 5.2%, respectively. In patients with RLC ≤ 13% at screening ( n = 74: Catumaxomab, 50 and control, 24), the median (mean) OS difference between the Catumaxomab and the control group was 3 (16) days, respectively ( P = 0.2561). Conclusions: OS was significantly improved after Catumaxomab treatment in patients with malignant ascites. An RLC > 13% at baseline was a significant prognostic biomarker. Clin Cancer Res; 20(12); 3348–57. ©2014 AACR .

  • Catumaxomab with and without prednisolone in patients with malignant ascites due to epithelial cancer: Results from the phase IIIb CASIMAS study.
    Journal of Clinical Oncology, 2012
    Co-Authors: Jalid Sehouli, Pauline Wimberger, Ignace Vergote, Per Rosenberg, Andreas Schneeweiss, Carsten Bokemeyer, Christoph Salat, Giovanni Scambia, Dominique Berton-rigaud, Salvatore Siena
    Abstract:

    e13097^ Background: The primary objective of this study was to compare Catumaxomab with prednisolone (CP) to Catumaxomab without prednisolone (C) as 3-hour intraperitoneal (i.p.) infusion by demonstrating superiority for safety and non-inferiority for efficacy of the CP arm. Methods: 219 patients were randomized to Catumaxomab plus premedication of 25 mg prednisolone (111 pts) or to Catumaxomab alone (108 pts). The primary endpoint was the composite safety score (CSS) summarizing the worst CTCAE grades for the main TEAEs (pyrexia, nausea, vomiting, and abdominal pain). A potential impact of prednisolone on efficacy was assessed by the co-primary endpoint puncture-free survival (PuFS). Further parameters included overall survival (OS) and time to next therapeutic puncture (TTPu). Results: The superiority of CP for safety was not proven as the mean CSS was comparable in the two groups (CP: 4.1; C: 3.8 for; p= 0.383). The median PuFS was slightly lower in CP (30 days) compared to C (37 days). However the haz...

  • Two-year follow-up of a phase II study on Catumaxomab as part of a multimodal approach in primarily resectable gastric cancer.
    Journal of Clinical Oncology, 2012
    Co-Authors: Carsten Bokemeyer, Djordje Atanackovic, Karsten Ridwelski, Dirk Arnold, Ewald Woell, Markus W. Büchler, Colin Krueger, Christoph Schuhmacher
    Abstract:

    4095^ Background: Perioperative chemotherapy (CT) has demonstrated as survival benefit in locally advanced gastric cancer (GC) in randomized trials. However, the overall cure rate is 30-40% and a significant number of patients are not able to receive the postoperative part of their CT regimen. In Europe, the trifunctional antibody Catumaxomab is approved for the treatment of malignant ascites based on a pivotal trial which also included GC patients. A new multimodal approach combining neoadjuvant CT, followed by gastrectomy and intraperitoneal (i.p.) immunotherapy with Catumaxomab was assessed in a single-arm multicenter phase II study. We here report 2-year follow-up data. Methods: GC pts (T2/T3/T4, N+/–, M0) received 3 cycles of neoadjuvant fluoropyrimidin/platinum-based CT followed by ’en-bloc’ R0-gastrectomy. Catumaxomab was administered i.p. as intraoperative bolus (10 µg) followed by 4 consecutive 3-hour infusions of 10-150 µg. Primary safety endpoint was the rate of predefined postoperative complic...

  • Catumaxomab: Pharmacodynamic and pharmacokinetic data from phase IIIb CASIMAS study in patients with malignant ascites.
    Journal of Clinical Oncology, 2012
    Co-Authors: Per Rosenberg, Ignace Vergote, Carsten Bokemeyer, Christoph Salat, Dominique Berton-rigaud, Alexander Serg Dudnitchenko, Vladimir Bondar, H. Havsteen, Xavier Durando, Pauline Wimberger
    Abstract:

    e13108^ Background: Catumaxomab (anti-EpCAM x anti-CD3) is approved in the EU for the i.p. locoregional treatment of malignant ascites (MA). The peritoneal cavity invaded by epithelial tumor cells ...

Jalid Sehouli - One of the best experts on this subject based on the ideXlab platform.

  • Detection of soluble EpCAM (sEpCAM) in malignant ascites predicts poor overall survival in patients treated with Catumaxomab
    Oncotarget, 2015
    Co-Authors: Andreas Seeber, Ioana Braicu, Gerold Untergasser, Mani Nassir, Dominic Fong, Laura Botta, Guenther Gastl, Heidi Fiegl, Alain G. Zeimet, Jalid Sehouli
    Abstract:

    EpCAM is an attractive target for cancer therapy and the EpCAM-specific antibody Catumaxomab has been used for intraperitoneal treatment of EpCAM-positive cancer patients with malignant ascites. New prognostic markers are necessary to select patients that mostly benefit from Catumaxomab. Recent data showed that soluble EpCAM (sEpCAM) is capable to block the effect of Catumaxomab in vitro. This exploratory retrospective analysis was performed on archived ascites samples to evaluate the predictive role of sEpCAM in Catumaxomab-treated patients. Sixty-six Catumaxomab-treated patients with an available archived ascites sample were included in this study and tested for sEpCAM by sandwich ELISA. All probes were sampled before treatment start and all patients received at least one Catumaxomab infusion. Overall survival, puncture-free survival and time to next puncture were compared between sEpCAM-positive and -negative patients. We detected sEpCAM in ascites samples of 9 patients (13.6%). These patients showed a significantly shorter overall survival. The prognostic significance of sEpCAM in ascites was particularly strong in patients with ovarian cancer. Puncture-free survival and time to next puncture were not significantly different between sEpCAM-positive and -negative patients. We propose sEpCAM in malignant ascites as a potential predictive marker in cancer patients treated with Catumaxomab. Prospective studies with larger patients samples are urgently needed to confirm these findings and studies testing dose-intensified Catumaxomab in patients with sEpCAM-positive ascites should be envisaged.

  • Re-challenge with Catumaxomab in patients with malignant ascites: results from the SECIMAS study
    Medical oncology (Northwood London England), 2014
    Co-Authors: Klaus Pietzner, Ignace Vergote, Per Rosenberg, Radoslav Chekerov, Armando Santoro, Frederik Marmé, Holger Martinius, Hilke Friccius-quecke, Jalid Sehouli
    Abstract:

    Malignant ascites is a common phenomenon in cancer patients. It poses a great challenge to the clinician, because of limited treatment options and strong impairment of the quality of life of the often palliative patients. The SECIMAS study investigated the feasibility of a re-chal- lenge with four Catumaxomab intraperitoneal infusions in patients who had already received a first cycle of four infusions in the phase III CASIMAS study, which com- pared Catumaxomab with and without prednisolone pre- medication. The primary endpoint was the proportion of patients who received at least three Catumaxomab infu- sions. Secondary endpoints included a composite safety score (CSS) summarising the worst grades for the main Catumaxomab-related adverse events (pyrexia, nausea, vomiting and abdominal pain), safety, efficacy and the occurrence of anti-drug antibodies (ADAs). Eight of nine screened patients received a second Catumaxomab cycle. Compliance with a Catumaxomab re-challenge was high: all eight patients (100 %) received all four infusions. The median CSS was 3.0 versus 3.4 in CASIMAS. The toler- ability profile of the second Catumaxomab cycle was comparable to that of the first cycle. Median puncture-free survival (48 days) and overall survival (407 days) were longer than in CASIMAS (35 and 103 days, respectively), although median time to next puncture was shorter (60 vs. 97 days). Of six patients sampled, all were ADA positive at screening and remained ADA positive until the end of the study. The presence of ADAs did not affect catumax- omab's safety or efficacy. The CSS and tolerability profile for Catumaxomab in SECIMAS were comparable to those in CASIMAS. The majority of patients benefitted from a second cycle of Catumaxomab. A re-challenge seems to be feasible and safe for selected patients with recurrent malignant ascites due to carcinoma after a first cycle of Catumaxomab.

  • Intra- and postoperative Catumaxomab in patients with epithelial ovarian cancer: safety and two-year efficacy results from a multicentre, single-arm, phase II study.
    British journal of cancer, 2014
    Co-Authors: Jalid Sehouli, A Reinthaller, C Marth, D Reimer, T Reimer, W Stummvoll, L Angleitner-boubenizek, B Brandt, Radoslav Chekerov
    Abstract:

    Intra- and postoperative Catumaxomab in patients with epithelial ovarian cancer: safety and two-year efficacy results from a multicentre, single-arm, phase II study

  • Catumaxomab with and without prednisolone premedication for the treatment of malignant ascites due to epithelial cancer: Results of the randomised phase IIIb CASIMAS study
    Medical oncology (Northwood London England), 2014
    Co-Authors: Jalid Sehouli, Klaus Pietzner, Pauline Wimberger, Ignace Vergote, Per Rosenberg, Andreas Schneeweiss, Carsten Bokemeyer, Christoph Salat, Giovanni Scambia, Dominique Berton-rigaud
    Abstract:

    This two-arm, randomised, multicentre, open-label, phase IIIb study investigated the safety and efficacy of a 3-h Catumaxomab infusion with/without prednisolone premedication to reduce Catumaxomab-related adverse events. Patients with malignant ascites due to epithelial cancer received four 3-h intraperitoneal Catumaxomab infusions with/without intravenous prednisolone (25 mg) premedication before each infusion. The primary safety endpoint was a composite safety score calculated from the incidence and intensity of the most frequent Catumaxomab-related adverse events (pyrexia, nausea, vomiting and abdominal pain). Puncture-free survival (PuFS) was a co-primary endpoint. Time to next puncture (TTPu) and overall survival (OS) were secondary endpoints. Prednisolone premedication did not result in a significant reduction in the main Catumaxomab-related adverse events. The mean composite safety score was comparable in both arms (Catumaxomab plus prednisolone, 4.1; Catumaxomab, 3.8; p = 0.383). Median PuFS (30 vs. 37 days) and TTPu (78 vs. 102 days) were shorter in the Catumaxomab plus prednisolone arm than in the Catumaxomab arm, but the differences were not statistically significant (p = 0.402 and 0.599, respectively). Median OS was longer in the Catumaxomab plus prednisolone arm than in the Catumaxomab arm (124 vs. 86 days), but the difference was not statistically significant (p = 0.186). The superiority of Catumaxomab plus prednisolone versus Catumaxomab alone could not be proven for the primary endpoint. Prednisolone did not result in a significant reduction in the main Catumaxomab-related adverse events. The study confirms the safety and efficacy of Catumaxomab administered as four 3-h intraperitoneal infusions for the treatment of malignant ascites.

  • Results of a phase II clinical trial to evaluate a re-challenge of intraperitoneal Catumaxomab for treatment of malignant ascites (MA) due to epithelial cancer (SECIMAS).
    Journal of Clinical Oncology, 2013
    Co-Authors: Klaus Pietzner, Ignace Vergote, Per Rosenberg, Armando Santoro, Frederik Marmé, Hilke Friccius-quecke, Jalid Sehouli
    Abstract:

    5582 Background: Catumaxomab is approved in Europe for the i.p. treatment of MA. With a growing number of patients (pts) treated, the question arises, if a re-challenge is feasible and effective despite the immunogenicity of this non-humanised antibody. Methods: Pts were eligible if they received 4 i.p. applications of Catumaxomab in the CASIMAS study and benefitted with a puncture free interval of > 60 days. Primary endpoint was to determine the proportion of pts who were able to receive at least 3 Catumaxomab applications. Secondary endpoints were the development of human anti-drug antibodies (ADA) as well as the safety profile of a second Catumaxomab cycle including a composite safety score (CSS) summarizing the worst CTCAE grades for the main adverse reactions (pyrexia, nausea, vomiting, abdominal pain). Efficacy endpoints were time to puncture (TTPu), overall survival (OS) and puncture-free survival (PuFS). Results: Median age was 59.0 years. 8 out of 9 screened pts were treated with a second cycle o...

D. Seimetz - One of the best experts on this subject based on the ideXlab platform.

  • The Role of Relative Lymphocyte Count as a Biomarker for the Effect of Catumaxomab on Survival in Malignant Ascites Patients: Results from a Phase II/III Study
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2014
    Co-Authors: Markus M. Heiss, Carsten Bokemeyer, Michael A. Ströhlein, D. Arnold, Simon L. Parsons, D. Seimetz, Horst Lindhofer, Elisabeth Schulze, Michael Hennig
    Abstract:

    Purpose: We report the role of relative lymphocyte count (RLC) as a potential biomarker with prognostic impact for Catumaxomab efficacy and overall survival (OS) based on a post hoc analysis of the pivotal phase II/III study of intraperitoneal Catumaxomab treatment of malignant ascites. Experimental Design: The impact of treatment and RLC on OS was evaluated using multivariate Cox models. Kaplan–Meier and log-rank tests were used for group comparisons. Survival analyses were performed on the safety population [patients with paracentesis plus ≥1 dose of Catumaxomab ( n = 157) and paracentesis alone ( n = 88)]. Determination of the optimal cutoff value for RLC was based on five optimality criteria. Results: OS was significantly longer with Catumaxomab versus paracentesis alone ( P = 0.0219). The 6-month OS rate with Catumaxomab was 28.9% versus 6.7% with paracentesis alone. RLC had a positive impact on OS and was an independent prognostic factor ( P 13% ( n = 159: Catumaxomab, 100 and control, 59), Catumaxomab was associated with a favorable effect on OS versus paracentesis alone ( P = 0.0072), with a median/mean OS benefit of 41/131 days and an increased 6-month survival rate of 37.0% versus 5.2%, respectively. In patients with RLC ≤ 13% at screening ( n = 74: Catumaxomab, 50 and control, 24), the median (mean) OS difference between the Catumaxomab and the control group was 3 (16) days, respectively ( P = 0.2561). Conclusions: OS was significantly improved after Catumaxomab treatment in patients with malignant ascites. An RLC > 13% at baseline was a significant prognostic biomarker. Clin Cancer Res; 20(12); 3348–57. ©2014 AACR .

  • Humoral response to Catumaxomab correlates with clinical outcome: Results of the pivotal phase II/III study in patients with malignant ascites
    International journal of cancer, 2011
    Co-Authors: Marion G. Ott, Michael Hennig, Horst Lindhofer, Rolf Linke, Frederik Marmé, Gerhard Moldenhauer, Rolf Spannagl, Mirko M. Essing, D. Seimetz
    Abstract:

    The trifunctional antibody Catumaxomab is a targeted immunotherapy for the intraperitoneal treatment of malignant ascites. In a Phase II/III trial in cancer patients (n = 258) with malignant ascites, Catumaxomab showed a clear clinical benefit vs. paracentesis and had an acceptable safety profile. Human antimouse antibodies (HAMAs), which could be associated with beneficial humoral effects and prolonged survival, may develop against Catumaxomab as it is a mouse/rat antibody. This post hoc analysis investigated whether there was a correlation between the detection of HAMAs 8 days after the fourth Catumaxomab infusion and clinical outcome. HAMA-positive and HAMA-negative patients in the Catumaxomab group and patients in the control group were analyzed separately for all three clinical outcome measures (puncture-free survival, time to next puncture and overall survival) and compared to each other. There was a strong correlation between humoral response and clinical outcome: patients who developed HAMAs after Catumaxomab showed significant improvement in all three clinical outcome measures vs. HAMA-negative patients. In the overall population in HAMA-positive vs. HAMA-negative patients, median puncture-free survival was 64 vs. 27 days (p < 0.0001; HR 0.330), median time to next therapeutic puncture was 104 vs. 46 days (p = 0.0002; HR 0.307) and median overall survival was 129 vs. 64 days (p = 0.0003; HR 0.433). Similar differences between HAMA-positive and HAMA-negative patients were seen in the ovarian, nonovarian and gastric cancer subgroups. In conclusion, HAMA development may be a biomarker for Catumaxomab response and patients who developed HAMAs sooner derived greater benefit from Catumaxomab treatment.

  • The effect of the trifunctional anti-EpCAM antibody Catumaxomab on the development of tumor-specific immune responses in patients with gastric cancer.
    Journal of Clinical Oncology, 2011
    Co-Authors: Henrike Reinhard, Carsten Bokemeyer, D. Seimetz, Sabrina Meyer, Katrin Bartels, R. Fischer, Djordje Atanackovic
    Abstract:

    2601 Background: The abundant expression of the epithelial cell-adhesion molecule EpCAM on the surface of epithelial cancer cells renders it an attractive target for immunotherapy of gastric cancer (GC). The trifunctional antibody (Ab) Catumaxomab targets EpCAM on malignant cells and CD3 on T cells while triggering antigen (Ag)-presenting cells via their Fcγ-receptor. Recently, Catumaxomab has received approval for the treatment of malignant ascites; however, the exact immune mechanisms behind its clinical effects are unknown. Methods: In a phase II study, patients with operable GC received neoadjuvant chemotherapy followed by 1 dose of Catumaxomab during surgery and 4 consecutive doses applied intraperitoneally in the adjuvant setting. We measured the immunomodulatory effects of Catumaxomab in 6 patients at 3 time points: before surgery, after application of the first dose, and 1 month post treatment. Results: None of the patients had evidence of autologous EpCAM-specific Ab responses. However, the major...

  • Catumaxomab administered as a 3-hour intraperitoneal infusion: Results from an integrated safety analysis.
    Journal of Clinical Oncology, 2011
    Co-Authors: Barbara Schmalfeldt, Michael Hennig, D. Seimetz, H. Gamperl, D. Finas, J. Schilling, H. Oettle, T. Ligensa, A. Kainz
    Abstract:

    e13058 Background: Catumaxomab (anti-EpCAM x anti-CD3) is approved in the EU for the intraperitoneal treatment of malignant ascites with an infusion time of 6 hours (h), as used in the pivotal phase II/III clinical study. Experience with a 3-h infusion has grown substantially as all studies conducted thereafter used a reduced 3-h infusion time. Methods: An integrated safety analysis (ISA) comprising 5 completed studies of patients with ovarian or gastric cancer and without malignant ascites treated with a 3-h Catumaxomab infusion was conducted. In 4 of 5 studies, Catumaxomab was administered in a perioperative setting. This 3-h database (ISA-3 h) was compared with the reference database (ISA-6 h) of the 6-h Catumaxomab infusion, which mainly includes patients with malignant ascites. Symptomatic adverse drug reactions (ADRs) of intensity grade ≥3 occurring in ≥1% of patients were used to describe the safety profiles derived from the ISA-6 h (N=258) and ISA-3 h (N=125) databases. Results: The nature of thes...

  • Humoral tumor-associated immune responses induced by Catumaxomab in patients with malignant ascites.
    Journal of Clinical Oncology, 2011
    Co-Authors: Peter Ruf, Michael Jäger, D. Seimetz, H. Martinius, B. Foerster, Horst Lindhofer
    Abstract:

    2575 Background: Catumaxomab is the first EU approved bispecific (anti-EpCAM x anti-CD3) trifunctional antibody for the intraperitoneal (ip) treatment of malignant ascites (MA) in patients (pts) wi...