Abstract
Background: L19-IL2, a tumour-targeting immunocytokine composed of the recombinant human antibody fragment L19 (specific to the alternatively-spliced EDB domain of fibronectin, a well characterised marker of tumour neo-vasculature) and of human IL2, has demonstrated strong therapeutic activity in animal cancer models. This phase I/II trial was performed to evaluate safety, tolerability, recommended phase II dose (RD) and early signs of activity of L19-IL2. Patients and methods: Five cohorts of patients with progressive solid tumours (n = 21) received an intravenous infusion of L19-IL2 (from 5 to 30 Mio IU IL2 equivalent dose) on days 1, 3 and 5 every 3 weeks. This treatment cycle was repeated up to six times. In the following expansion phase, patients with metastatic renal cell carcinoma (RCC) (n = 12) were treated at the RD of L19-IL2. Clinical data and laboratory findings were analysed for safety, tolerability and activity. Results: Preclinical studies in rats and monkeys did not raise any safety concerns. The RD was defined to be 22.5 Mio IU IL2 equivalent. Pharmacokinetics of L19-IL2 was dose proportional over the tested range, with a terminal half-life of 2-3 h. Toxicities were manageable and reversible with no treatment-related deaths. We observed stable disease in 17/33 patients (51%) and 15/18 with mRCC (83%) after two cycles. Median progression-free survival of RCC patients in the expansion phase of the study was 8 months (1.5-30.5). Conclusions: L19-IL2 can be safely and repeatedly administered at the RD of 22.5 Mio IU IL2 equivalent in advanced solid tumours. Preliminary evaluation suggests clinical activity of L19-IL2 in patients with mRCC.
| Original language | English |
|---|---|
| Pages (from-to) | 2926-2935 |
| Number of pages | 10 |
| Journal | European Journal of Cancer |
| Volume | 46 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - Nov 2010 |
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Keywords
- Immunotherapy
- Phase I/II study
- Renal cell carcinoma
- Solid tumours
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
The tumour-targeting human L19-IL2 immunocytokine : Preclinical safety studies, phase i clinical trial in patients with solid tumours and expansion into patients with advanced renal cell carcinoma. / Johannsen, Manfred; Spitaleri, Gianluca; Curigliano, Giuseppe; Roigas, Jan; Weikert, Steffen; Kempkensteffen, Carsten; Roemer, Andreas; Kloeters, Christian; Rogalla, Patrik; Pecher, Gabriele; Miller, Kurt; Berndt, Alexander; Kosmehl, Hartwig; Trachsel, Eveline; Kaspar, Manuela; Lovato, Valeria; González-Iglesias, Reinerio; Giovannoni, Leonardo; Menssen, Hans D.; Neri, Dario; De Braud, Filippo.
In: European Journal of Cancer, Vol. 46, No. 16, 11.2010, p. 2926-2935.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The tumour-targeting human L19-IL2 immunocytokine
T2 - Preclinical safety studies, phase i clinical trial in patients with solid tumours and expansion into patients with advanced renal cell carcinoma
AU - Johannsen, Manfred
AU - Spitaleri, Gianluca
AU - Curigliano, Giuseppe
AU - Roigas, Jan
AU - Weikert, Steffen
AU - Kempkensteffen, Carsten
AU - Roemer, Andreas
AU - Kloeters, Christian
AU - Rogalla, Patrik
AU - Pecher, Gabriele
AU - Miller, Kurt
AU - Berndt, Alexander
AU - Kosmehl, Hartwig
AU - Trachsel, Eveline
AU - Kaspar, Manuela
AU - Lovato, Valeria
AU - González-Iglesias, Reinerio
AU - Giovannoni, Leonardo
AU - Menssen, Hans D.
AU - Neri, Dario
AU - De Braud, Filippo
PY - 2010/11
Y1 - 2010/11
N2 - Background: L19-IL2, a tumour-targeting immunocytokine composed of the recombinant human antibody fragment L19 (specific to the alternatively-spliced EDB domain of fibronectin, a well characterised marker of tumour neo-vasculature) and of human IL2, has demonstrated strong therapeutic activity in animal cancer models. This phase I/II trial was performed to evaluate safety, tolerability, recommended phase II dose (RD) and early signs of activity of L19-IL2. Patients and methods: Five cohorts of patients with progressive solid tumours (n = 21) received an intravenous infusion of L19-IL2 (from 5 to 30 Mio IU IL2 equivalent dose) on days 1, 3 and 5 every 3 weeks. This treatment cycle was repeated up to six times. In the following expansion phase, patients with metastatic renal cell carcinoma (RCC) (n = 12) were treated at the RD of L19-IL2. Clinical data and laboratory findings were analysed for safety, tolerability and activity. Results: Preclinical studies in rats and monkeys did not raise any safety concerns. The RD was defined to be 22.5 Mio IU IL2 equivalent. Pharmacokinetics of L19-IL2 was dose proportional over the tested range, with a terminal half-life of 2-3 h. Toxicities were manageable and reversible with no treatment-related deaths. We observed stable disease in 17/33 patients (51%) and 15/18 with mRCC (83%) after two cycles. Median progression-free survival of RCC patients in the expansion phase of the study was 8 months (1.5-30.5). Conclusions: L19-IL2 can be safely and repeatedly administered at the RD of 22.5 Mio IU IL2 equivalent in advanced solid tumours. Preliminary evaluation suggests clinical activity of L19-IL2 in patients with mRCC.
AB - Background: L19-IL2, a tumour-targeting immunocytokine composed of the recombinant human antibody fragment L19 (specific to the alternatively-spliced EDB domain of fibronectin, a well characterised marker of tumour neo-vasculature) and of human IL2, has demonstrated strong therapeutic activity in animal cancer models. This phase I/II trial was performed to evaluate safety, tolerability, recommended phase II dose (RD) and early signs of activity of L19-IL2. Patients and methods: Five cohorts of patients with progressive solid tumours (n = 21) received an intravenous infusion of L19-IL2 (from 5 to 30 Mio IU IL2 equivalent dose) on days 1, 3 and 5 every 3 weeks. This treatment cycle was repeated up to six times. In the following expansion phase, patients with metastatic renal cell carcinoma (RCC) (n = 12) were treated at the RD of L19-IL2. Clinical data and laboratory findings were analysed for safety, tolerability and activity. Results: Preclinical studies in rats and monkeys did not raise any safety concerns. The RD was defined to be 22.5 Mio IU IL2 equivalent. Pharmacokinetics of L19-IL2 was dose proportional over the tested range, with a terminal half-life of 2-3 h. Toxicities were manageable and reversible with no treatment-related deaths. We observed stable disease in 17/33 patients (51%) and 15/18 with mRCC (83%) after two cycles. Median progression-free survival of RCC patients in the expansion phase of the study was 8 months (1.5-30.5). Conclusions: L19-IL2 can be safely and repeatedly administered at the RD of 22.5 Mio IU IL2 equivalent in advanced solid tumours. Preliminary evaluation suggests clinical activity of L19-IL2 in patients with mRCC.
KW - Immunotherapy
KW - Phase I/II study
KW - Renal cell carcinoma
KW - Solid tumours
UR - http://www.scopus.com/inward/record.url?scp=78049264752&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78049264752&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2010.07.033
DO - 10.1016/j.ejca.2010.07.033
M3 - Article
C2 - 20797845
AN - SCOPUS:78049264752
VL - 46
SP - 2926
EP - 2935
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 16
ER -