A phase I study of PankoMab-GEX, a humanised glyco-optimised monoclonal antibody to a novel tumour-specific MUC1 glycopeptide epitope in patients with advanced carcinomas.
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.



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).



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.



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.
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.
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Fiedler
Oncology Institute of Southern Switzerland, Ospedale Regionale Bellinzona e Valli, 6500 Bellinzona, Switzerland. Electronic address: Sara.DeDosso@eoc.ch.
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DeDosso
Fondazione IRCCS, Istituto Nazionale dei Tumori, Via G. Venezian 1, 20133 Milano, Italy. Electronic address: Sara.Cresta@istitutotumori.mi.it.
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Cresta
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.
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Weidmann
Fondazione IRCCS, Istituto Nazionale dei Tumori, Via G. Venezian 1, 20133 Milano, Italy.
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Tessari
Glycotope GmbH, Robert-Roessle-Str. 10, 13125 Berlin, Germany. Electronic address: marc.salzberg@glycotope.com.
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Salzberg
Glycotope GmbH, Robert-Roessle-Str. 10, 13125 Berlin, Germany. Electronic address: bruno.dietrich@glycotope.com.
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Dietrich
Glycotope GmbH, Robert-Roessle-Str. 10, 13125 Berlin, Germany. Electronic address: hans.baumeister@glycotope.com.
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Baumeister
Glycotope GmbH, Robert-Roessle-Str. 10, 13125 Berlin, Germany. Electronic address: steffen.goletz@glycoytope.com.
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Goletz
Department of Medical Oncology, Ospedale San Raffaele, Via Olgettina 60, 20132 Milano, Italy. Electronic address: gianni.luca@hsr.it.
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Gianni
Oncology Institute of Southern Switzerland, Ospedale Regionale Bellinzona e Valli, 6500 Bellinzona, Switzerland. Electronic address: cristiana.sessa@eoc.ch.
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Sessa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D000939:Epitopes; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000939:Epitopes; D018396:Mucin-1; C581698:PankoMab-GEX
Glyco-optimised monoclonal antibody; Glycopeptide epitope; MUC1; Phase I; Solid tumours