A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors
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A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors. / Kebenko, Maxim; Goebeler, Marie-Elisabeth; Wolf, Martin; Hasenburg, Annette; Seggewiss-Bernhardt, Ruth; Ritter, Barbara; Rautenberg, Beate; Atanackovic, Djordje; Kratzer, Andrea; Rottman, James B; Friedrich, Matthias; Vieser, Eva; Elm, Stefanie; Patzak, Ingrid; Wessiepe, Dorothea; Stienen, Sabine; Fiedler, Walter.
in: ONCOIMMUNOLOGY, Jahrgang 7, Nr. 8, 2018, S. e1450710.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors
AU - Kebenko, Maxim
AU - Goebeler, Marie-Elisabeth
AU - Wolf, Martin
AU - Hasenburg, Annette
AU - Seggewiss-Bernhardt, Ruth
AU - Ritter, Barbara
AU - Rautenberg, Beate
AU - Atanackovic, Djordje
AU - Kratzer, Andrea
AU - Rottman, James B
AU - Friedrich, Matthias
AU - Vieser, Eva
AU - Elm, Stefanie
AU - Patzak, Ingrid
AU - Wessiepe, Dorothea
AU - Stienen, Sabine
AU - Fiedler, Walter
PY - 2018
Y1 - 2018
N2 - We assessed the tolerability and antitumor activity of solitomab, a bispecific T-cell engager (BiTE®) antibody construct targeting epithelial cell adhesion molecule (EpCAM). Patients with relapsed/refractory solid tumors not amenable to standard therapy received solitomab as continuous IV infusion in a phase 1 dose-escalation study with six different dosing schedules. The primary endpoint was frequency and severity of adverse events (AEs). Secondary endpoints included pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. Sixty-five patients received solitomab at doses between 1 and 96 µg/day for ≥28 days. Fifteen patients had dose-limiting toxicities (DLTs): eight had transient abnormal liver parameters shortly after infusion start or dose escalation (grade 3, n = 4; grade 4, n = 4), and one had supraventricular tachycardia (grade 3); all events resolved with solitomab discontinuation. Six patients had a DLT of diarrhea: four events resolved (grade 3, n = 3; grade 4, n = 1), one (grade 3) was ongoing at the time of treatment-unrelated death, and one (grade 3) progressed to grade 5 after solitomab discontinuation. The maximum tolerated dose was 24 µg/day. Overall, 95% of patients had grade ≥3 treatment-related AEs, primarily diarrhea, elevated liver parameters, and elevated lipase. Solitomab half-life was 4.5 hours; serum levels plateaued within 24 hours. One unconfirmed partial response was observed. In this study of a BiTE® antibody construct targeting solid tumors, treatment of relapsed/refractory EpCAM-positive solid tumors with solitomab was associated with DLTs, including severe diarrhea and increased liver enzymes, which precluded dose escalation to potentially therapeutic levels.
AB - We assessed the tolerability and antitumor activity of solitomab, a bispecific T-cell engager (BiTE®) antibody construct targeting epithelial cell adhesion molecule (EpCAM). Patients with relapsed/refractory solid tumors not amenable to standard therapy received solitomab as continuous IV infusion in a phase 1 dose-escalation study with six different dosing schedules. The primary endpoint was frequency and severity of adverse events (AEs). Secondary endpoints included pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. Sixty-five patients received solitomab at doses between 1 and 96 µg/day for ≥28 days. Fifteen patients had dose-limiting toxicities (DLTs): eight had transient abnormal liver parameters shortly after infusion start or dose escalation (grade 3, n = 4; grade 4, n = 4), and one had supraventricular tachycardia (grade 3); all events resolved with solitomab discontinuation. Six patients had a DLT of diarrhea: four events resolved (grade 3, n = 3; grade 4, n = 1), one (grade 3) was ongoing at the time of treatment-unrelated death, and one (grade 3) progressed to grade 5 after solitomab discontinuation. The maximum tolerated dose was 24 µg/day. Overall, 95% of patients had grade ≥3 treatment-related AEs, primarily diarrhea, elevated liver parameters, and elevated lipase. Solitomab half-life was 4.5 hours; serum levels plateaued within 24 hours. One unconfirmed partial response was observed. In this study of a BiTE® antibody construct targeting solid tumors, treatment of relapsed/refractory EpCAM-positive solid tumors with solitomab was associated with DLTs, including severe diarrhea and increased liver enzymes, which precluded dose escalation to potentially therapeutic levels.
KW - Journal Article
U2 - 10.1080/2162402X.2018.1450710
DO - 10.1080/2162402X.2018.1450710
M3 - SCORING: Journal article
C2 - 30221040
VL - 7
SP - e1450710
JO - ONCOIMMUNOLOGY
JF - ONCOIMMUNOLOGY
SN - 2162-402X
IS - 8
ER -
