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Tumor Discovery EpCAM-targeting cancer immunotherapies

monoclonal antibodies. Specifically, the antibody binds doses, and 12 patients in the study received the full dose.
to three different cell types: dendritic cells, macrophages, All patients had a histologically confirmed diagnosis
and NK cells – the immune system’s accessory cells which of gastric cancer, including metastatic esophagogastric
are activated when the Fc region binds to type I, IIa, and junction cancer types II and III, macroscopic peritoneal
III Fcγ receptors on these cells. In 2010, a pivotal clinical carcinomatosis (stages P1–4 according to Gilly’s
study led by Heiss et al. was conducted to investigate the classification), and an ECOG performance status of 0 or
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efficacy of catumaxomab in treating malignant ascites, a 1. Patients were also required to have a life expectancy of
common occurrence in aggressive cancers. A randomized at least 12 weeks, be medically fit to undergo gastrectomy
phase II/III clinical trial was conducted in patients with after primary systemic and intraperitoneal treatment and
EpCAM-positive tumors. In the trial, cancer patients (n = have adequate organ function. Regarding exclusion criteria,
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258) with recurrent symptomatic malignant ascites resistant patients with clinically significant cardiovascular disease
to conventional treatment were randomly assigned to within the past year, a history of human immunodeficiency
receive either paracentesis abdominis plus catumaxomab virus infection, chronic hepatitis B or C, active and
(experimental group) or to undergo paracentesis alone clinically serious infection, pre-existing neuropathy higher
(control group). The catumaxomab treatment involved than grade 1, or distant metastasis other than peritoneal
intraperitoneal administration on days 0, 3, 7, and 10 at carcinomatosis were deemed ineligible for enrolment. In
doses of 10, 20, 50, and 150 µg, respectively. The results this study design, catumaxomab was administered every
demonstrated that patients in the experimental group 3 days over a 10-day cycle using a constant infusion pump
had significantly increased puncture-free survival time system to control the delivery of the drug over a period
following paracentesis compared to the control group, of 3 h. Dosage escalation from 10 to 150 µg was initiated
with durations of 46 days versus 11 days and 77 days before the administration of catumaxomab and the
versus 13 days, respectively. In addition, patients treated intravenous injection of 1 g of paracetamol as prophylaxis
with catumaxomab exhibited fewer signs and symptoms for cytokine-release-associated symptoms. After 7 days
of ascites compared to the control group, with an overall and the final infusion of catumaxomab, six cycles of FLOT
survival of 77 days versus 44 days. The reported side effects chemotherapy were administered. The regimen consisted
were generally reversible and primarily associated with of 5-fluorouracil (2600 mg/m² as a 24-h infusion on day 1),
the immunologic mode of action. Overall, catumaxomab leucovorin (200 mg/m² on day 1), oxaliplatin (85 mg/m²
demonstrated a clear therapeutic benefit with an acceptable on day 1), and docetaxel (50 mg/m² on day 1), delivered
safety profile in patients with malignant ascites caused every 2 weeks. The median follow-up period for patients
by epithelial malignancies, particularly in gastric cancer. was 52 months. Observed side effects (grade 3 – 4)
This finding contradicts the results of a similar study in associated with catumaxomab included nausea, elevated
which a subset of patients with malignant pleural effusion levels of liver enzymes and bilirubin, and abdominal pain.
who were administered with catumaxomab developed The authors did not observe any significant differences
severe dose-limiting toxicities, including fatal sepsis, in median progression-free survival and overall survival
grade 3 erythema, and hepatobiliary tract disorders. This between the various treatment strategies. The addition of
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further raises concerns regarding patient selection and the catumaxomab to chemotherapy was well tolerated and
mechanism of action of catumaxomab. In this context, feasible for advanced gastric cancer. Although the study
successive evaluations of catumaxomab have concentrated did not demonstrate an improvement in the macroscopic
on its use for palliative intents for patients with late- complete remission rate of peritoneal carcinomatosis,
stage diseases characterized by significant tumor burden catumaxomab exhibited an acceptable safety profile, and
associated with malignant ascites. 33,34 Further evaluation the addition of chemotherapy did not result in unexpected
of catumaxomab was conducted to compare intravenous adverse reactions. Another anti-EpCAM BiTE, known
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to intraperitoneal routes of administration. This is based as solitomab, MT110, or AMG 110, was developed by
on the premise that there is a positive correlation in the Amgen. In a recent clinical trial, the bispecific single-
increased accumulation of fluid in the peritoneal cavity of chain antibody (scFv) construct/bispecific T-cell-engaging
patients with EpCAM-positive tumors. 35 solitomab demonstrated efficacy in patients with refractory

A multicenter, prospective, randomized, open-label solid tumors. 37,38 This multicenter phase I study enrolled
phase II study consisting of 31 patients (≥18 years), with 65 patients who received varying doses (ranging between
15 patients receiving catumaxomab and chemotherapy 1 and 96 µg/day) of solitomab via continuous intravenous
with 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel infusion over a period of approximately 28 days. Following
(FLOT), and 16 patients receiving only FLOT, was treatment, 15 patients experienced dose-limiting toxicities,
conducted. A full set of catumaxomab consisted of four whereas eight patients exhibited transient abnormal
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Volume 4 Issue 1 (2025) 6 doi: 10.36922/td.4926