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.
| Original language | English |
|---|---|
| Pages (from-to) | 55-63 |
| Number of pages | 9 |
| Journal | European Journal of Cancer |
| Volume | 63 |
| DOIs | |
| Publication status | Published - Aug 1 2016 |
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Keywords
- Glyco-optimised monoclonal antibody
- Glycopeptide epitope
- MUC1
- Phase I
- Solid tumours
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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. / Fiedler, W.; Dedosso, S.; Cresta, Sara; Weidmann, J.; Tessari, Anna; Salzberg, M.; Dietrich, B.; Baumeister, H.; Goletz, Steffen; Gianni, Luca; Sessa, C.
In: European Journal of Cancer, Vol. 63, 01.08.2016, p. 55-63.Research output: Contribution to journal › Article
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TY - JOUR
T1 - 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
AU - Fiedler, W.
AU - Dedosso, S.
AU - Cresta, Sara
AU - Weidmann, J.
AU - Tessari, Anna
AU - Salzberg, M.
AU - Dietrich, B.
AU - Baumeister, H.
AU - Goletz, Steffen
AU - Gianni, Luca
AU - Sessa, C.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - Glyco-optimised monoclonal antibody
KW - Glycopeptide epitope
KW - MUC1
KW - Phase I
KW - Solid tumours
UR - http://www.scopus.com/inward/record.url?scp=84974621186&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84974621186&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2016.05.003
DO - 10.1016/j.ejca.2016.05.003
M3 - Article
VL - 63
SP - 55
EP - 63
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -