TY - JOUR
T1 - A multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or lower oesophagus
T2 - The MONO study
AU - Türeci, O.
AU - Sahin, U.
AU - Schulze-Bergkamen, H.
AU - Zvirbule, Z.
AU - Lordick, F.
AU - Koeberle, D.
AU - Thuss-Patience, P.
AU - Ettrich, T.
AU - Arnold, D.
AU - Bassermann, F.
AU - Al-Batran, S. E.
AU - Wiechen, K.
AU - Dhaene, K.
AU - Maurus, D.
AU - Gold, M.
AU - Huber, C.
AU - Krivoshik, A.
AU - Arozullah, A.
AU - Park, J. W.
AU - Schuler, M.
N1 - Publisher Copyright:
© 2019 The Author(s). Published by Oxford University Press on behalf of the European Society for Medical Oncology.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Background: Claudin 18.2 (CLDN18.2) is physiologically confined to gastric mucosa tight junctions; however, upon malignant transformation, perturbations in cell polarity lead to CLDN18.2 epitopes being exposed on the cancer cell surface. The first-in-class monoclonal antibody, zolbetuximab (formerly known as IMAB362), binds to CLDN18.2 and can induce immune-mediated lysis of CLDN18.2-positive cells. Patients and methods: Patients with advanced gastric, gastro-oesophageal junction (GEJ) or oesophageal adenocarcinomas with moderate-to-strong CLDN18.2 expression in ≥50% of tumour cells received zolbetuximab intravenously every 2 weeks for five planned infusions. At least three patients were enrolled in two sequential cohorts (cohort 1300 mg/m2; cohort 2600 mg/m2); additional patients were enrolled into a dose-expansion cohort (cohort 3600 mg/m2). The primary end point was the objective response rate [ORR: complete and partial response (PR)]; secondary end points included clinical benefit [ORR+stable disease (SD)], progression-free survival, safety/tolerability, and zolbetuximab pharmacokinetic profile. Results: From September 2010 to September 2012, 54 patients were enrolled (cohort 1, n = 4; cohort 2, n = 6; cohort 3, n = 44). Three patients in cohort 1 and 25 patients in cohorts 2/3 received at least 5 infusions. Antitumour activity data were available for 43 patients, of whom 4 achieved PR (ORR 9%) and 6 (14%) had SD for a clinical benefit rate of 23%. In a subgroup of patients with moderate-to-high CLDN18.2 expression in ≥70% of tumour cells, ORR was 14% (n = 4/29). Treatment-related adverse events occurred in 81.5% (n = 44/54) patients; nausea (61%), vomiting (50%), and fatigue (22%) were the most frequent. Conclusions: Zolbetuximab monotherapy was well tolerated and exhibited antitumour activity in patients with CLDN18.2-positive advanced gastric or GEJ adenocarcinomas, with response rates similar to those reported for single-agent targeted agents in gastric/GEJ cancer trials. ClinicalTrials.gov number: NCT01197885.
AB - Background: Claudin 18.2 (CLDN18.2) is physiologically confined to gastric mucosa tight junctions; however, upon malignant transformation, perturbations in cell polarity lead to CLDN18.2 epitopes being exposed on the cancer cell surface. The first-in-class monoclonal antibody, zolbetuximab (formerly known as IMAB362), binds to CLDN18.2 and can induce immune-mediated lysis of CLDN18.2-positive cells. Patients and methods: Patients with advanced gastric, gastro-oesophageal junction (GEJ) or oesophageal adenocarcinomas with moderate-to-strong CLDN18.2 expression in ≥50% of tumour cells received zolbetuximab intravenously every 2 weeks for five planned infusions. At least three patients were enrolled in two sequential cohorts (cohort 1300 mg/m2; cohort 2600 mg/m2); additional patients were enrolled into a dose-expansion cohort (cohort 3600 mg/m2). The primary end point was the objective response rate [ORR: complete and partial response (PR)]; secondary end points included clinical benefit [ORR+stable disease (SD)], progression-free survival, safety/tolerability, and zolbetuximab pharmacokinetic profile. Results: From September 2010 to September 2012, 54 patients were enrolled (cohort 1, n = 4; cohort 2, n = 6; cohort 3, n = 44). Three patients in cohort 1 and 25 patients in cohorts 2/3 received at least 5 infusions. Antitumour activity data were available for 43 patients, of whom 4 achieved PR (ORR 9%) and 6 (14%) had SD for a clinical benefit rate of 23%. In a subgroup of patients with moderate-to-high CLDN18.2 expression in ≥70% of tumour cells, ORR was 14% (n = 4/29). Treatment-related adverse events occurred in 81.5% (n = 44/54) patients; nausea (61%), vomiting (50%), and fatigue (22%) were the most frequent. Conclusions: Zolbetuximab monotherapy was well tolerated and exhibited antitumour activity in patients with CLDN18.2-positive advanced gastric or GEJ adenocarcinomas, with response rates similar to those reported for single-agent targeted agents in gastric/GEJ cancer trials. ClinicalTrials.gov number: NCT01197885.
KW - CLDN18.2
KW - IMAB362
KW - gastric cancer
KW - gastro-oesophageal junction adenocarcinoma
KW - zolbetuximab
UR - http://www.scopus.com/inward/record.url?scp=85072747287&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdz199
DO - 10.1093/annonc/mdz199
M3 - Article
C2 - 31240302
AN - SCOPUS:85072747287
SN - 0923-7534
VL - 30
SP - 1487
EP - 1495
JO - Annals of Oncology
JF - Annals of Oncology
IS - 9
ER -
