W Fiedler1, S DeDosso2, S Cresta3, J Weidmann4, A Tessari5, M Salzberg6, B Dietrich7, H Baumeister8, S Goletz9, L Gianni10, C Sessa11. 1. Hubertus-Wald University Cancer Center, Dept. of Medicine II, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: fiedler@uke.uni-hamburg.de. 2. Oncology Institute of Southern Switzerland, Ospedale Regionale Bellinzona e Valli, 6500 Bellinzona, Switzerland. Electronic address: Sara.DeDosso@eoc.ch. 3. Fondazione IRCCS, Istituto Nazionale dei Tumori, Via G. Venezian 1, 20133 Milano, Italy. Electronic address: Sara.Cresta@istitutotumori.mi.it. 4. Hubertus-Wald University Cancer Center, Dept. of Medicine II, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: j.weidmann@uke.de. 5. Fondazione IRCCS, Istituto Nazionale dei Tumori, Via G. Venezian 1, 20133 Milano, Italy. 6. Glycotope GmbH, Robert-Roessle-Str. 10, 13125 Berlin, Germany. Electronic address: marc.salzberg@glycotope.com. 7. Glycotope GmbH, Robert-Roessle-Str. 10, 13125 Berlin, Germany. Electronic address: bruno.dietrich@glycotope.com. 8. Glycotope GmbH, Robert-Roessle-Str. 10, 13125 Berlin, Germany. Electronic address: hans.baumeister@glycotope.com. 9. Glycotope GmbH, Robert-Roessle-Str. 10, 13125 Berlin, Germany. Electronic address: steffen.goletz@glycoytope.com. 10. Department of Medical Oncology, Ospedale San Raffaele, Via Olgettina 60, 20132 Milano, Italy. Electronic address: gianni.luca@hsr.it. 11. Oncology Institute of Southern Switzerland, Ospedale Regionale Bellinzona e Valli, 6500 Bellinzona, Switzerland. Electronic address: cristiana.sessa@eoc.ch.
Abstract
BACKGROUND: A phase I open-label dose-escalation study was conducted to define the safety, tolerability, and pharmacokinetics (PK) of PankoMab-GEX, a glyco-optimised humanised IgG1, with high affinity to a novel tumour-specific glycopeptide epitope of MUC1 (TA-MUC1) with excellent preclinical anti-tumour activity. PATIENTS AND METHODS: Seventy-four patients with advanced TA-MUC1-positive carcinomas received PankoMab-GEX intravenously every 3 (Q3W), 2 (Q2W), or 1 (QW) week in doses of 1-2200 mg in a three-plus-three dose-escalation design until disease progression (NCT01222624). RESULTS: No maximum tolerated dose was reached. Adverse events were mainly mild-to-moderate infusion-related reactions (IRRs) by the first infusion in 45% of patients. Only one dose-limiting toxicity, a grade III IRR, was observed. PankoMab-GEX exhibited linear PK over all doses. Mean terminal half-life was 189 ± 66 h (Q3W), without dose dependency. A target trough level ≥50 μg/mL was reached after one infusion with doses ≥1700 mg Q3W in 80% of patients. Clinical benefit in 60 evaluable patients included one complete response in a patient with ovarian cancer treated 483 d and confirmed disease stabilisation in 19 patients lasting a median (range) of 23 (10-109) weeks. All but two of the patients with clinical benefit had received a compounded total dose ≥700 mg over a 3-week period, including 8 of 12 (67%) patients with ovarian cancer. CONCLUSION: PankoMab-GEX is safe, well tolerated, and showed promising anti-tumour activity in advanced disease. A phase IIb study is ongoing evaluating the efficacy of PankoMab-GEX as a maintenance therapy in advanced ovarian cancer.
BACKGROUND: A phase I open-label dose-escalation study was conducted to define the safety, tolerability, and pharmacokinetics (PK) of PankoMab-GEX, a glyco-optimised humanised IgG1, with high affinity to a novel tumour-specific glycopeptide epitope of MUC1 (TA-MUC1) with excellent preclinical anti-tumour activity. PATIENTS AND METHODS: Seventy-four patients with advanced TA-MUC1-positive carcinomas received PankoMab-GEX intravenously every 3 (Q3W), 2 (Q2W), or 1 (QW) week in doses of 1-2200 mg in a three-plus-three dose-escalation design until disease progression (NCT01222624). RESULTS: No maximum tolerated dose was reached. Adverse events were mainly mild-to-moderate infusion-related reactions (IRRs) by the first infusion in 45% of patients. Only one dose-limiting toxicity, a grade III IRR, was observed. PankoMab-GEX exhibited linear PK over all doses. Mean terminal half-life was 189 ± 66 h (Q3W), without dose dependency. A target trough level ≥50 μg/mL was reached after one infusion with doses ≥1700 mg Q3W in 80% of patients. Clinical benefit in 60 evaluable patients included one complete response in a patient with ovarian cancer treated 483 d and confirmed disease stabilisation in 19 patients lasting a median (range) of 23 (10-109) weeks. All but two of the patients with clinical benefit had received a compounded total dose ≥700 mg over a 3-week period, including 8 of 12 (67%) patients with ovarian cancer. CONCLUSION: PankoMab-GEX is safe, well tolerated, and showed promising anti-tumour activity in advanced disease. A phase IIb study is ongoing evaluating the efficacy of PankoMab-GEX as a maintenance therapy in advanced ovarian cancer.
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