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Tumor Discovery EpCAM-targeting cancer immunotherapies

liver parameters shortly after infusion initiation or dose 8. Adoptive cell therapy (ACT)
escalation (grade 3, n = 4; grade 4, n = 4). In addition, one
patient experienced grade 3 supraventricular tachycardia Clinical trials of ACT-based immunotherapy against
EpCAM-positive cancers have expanded within the last
resulting in treatment discontinuation in all affected 5 years based on promising pre-clinical data. For example,
patients. Furthermore, six patients experienced dose- an anti-EpCAM nanobody Chimeric antigen receptor
limiting toxicity in the form of diarrhea. Among these six T-cells (CAR T) with dectin-1 costimulatory domain
patients, four (grade 3, n = 3; grade 4, n = 1) experienced demonstrated higher T-cell activation and less exhaustive
resolution, one (grade 3) still experienced symptoms at phenotypes in xenograph mouse models, a finding that
the time of treatment-unrelated death, and one (grade 3) led to the initiation of clinical evaluation. In the study,
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progressed to grade 5 after cessation of therapy. The the authors conducted a phase I clinical investigation by
MTD was determined to be 24 µg/day. Diarrhea, elevated enrolling 12 patients who were diagnosed with EpCAM-
liver parameters, and high lipase levels were the most positive epithelial tumors (NCT02915445). During the
frequently observed grade ≥3 treatment-related adverse study, 50% of patients experienced grade 1/2 toxicities.
events, occurring in 95% of patients. However, solitomab A total of 384 enrolled patients with multiple advanced-
exhibited a half-life of 4.5 h, and serum levels reached a stage cancer types have been administered with anti-
plateau within 1 day. The treatment of relapsed/refractory EpCAM CAR T. In addition, an anti-EpCAM (scFv) CAR
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EpCAM-positive solid tumors with solitomab, a BiTE ® T therapy, indicated for antigen-positive colon, esophagus,
antibody construct targeting solid tumors, resulted in pancreas, and prostate tumors, concluded its Phase I/II
dose-limiting toxicities, including severe diarrhea and recruiting 60 patients (NCT03013712) concluded in 2020
elevated liver enzymes, thereby impeding dose escalation without further information on study outcome (https://
to potential therapeutic levels. Despite achieving the clinicaltrials.gov/study/NCT03013712). In the study, a
key endpoints of assessing the frequency and severity novel CAR consisting of an anti-EpCAM(scFv) fused
of adverse events, as well as understanding its PKs and to two intracellular co-stimulatory signaling domains
antitumor activity, further investigation and exploration derived from CD3-zeta and CD28 was administered at the
are required. Table 1 presents a general overview of infusion dose of 1 – 10 × 10 modified T cells/kg. Table 2
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antibody-based targeted immunotherapies, which have provides a list of the ongoing and completed anti-EpCAM
either received approval or are currently in various stages CAR T clinical studies, with the majority still in early
of clinical evaluation. phases. Out of the 10 ongoing clinical trials, five are clinical
Table 1. Selected anti‑EpCAM antibody‑based immunotherapies that have been approved or currently undergoing clinical
evaluation
Product name/Clinical trial # Status Indications Reported adverse effects
Catumaxomab Approved • EpCAM-positive tumors Fever, nausea, vomiting, abdominal pain, and
• Malignant Ascites elevated liver enzymes
Edrecolomab (17-1A) Phase III • Mucinous adenocarcinoma of the colon High immunogenicity, short serum half-life
• Adenocarcinoma of colon
• Stage IIA – IIC colon cancer
Adecatumumab (MT201) Phase II • Metastatic breast cancer Chills, nausea, fatigue, and diarrhea
M701 Phase I • Malignant ascites Grade 1 adverse drug events
• Advanced solid tumors
EMD 273066 Phase I • EpCAM-positive ovarian and colorectal carcinomas Unknown
• Non-small-cell lung cancer
• Prostate cancer
ING-1 Phase I • Advanced adenocarcinomas Acute pancreatitis, asthenia
Citatuzumab bogatox Phase I • Advanced epithelial tumors Fever, hypotension, and hypoalbuminemia
Opportuzumab monatox Phase I and II • Squamous cell carcinoma of the head and neck Pain at the site of injection, mild-to-moderate
• Non-muscle invasive bladder cancer adverse effects
• In situ urothelial carcinoma of the bladder
MOC31PE Phase I • Advanced adenocarcinomas Reversible liver toxicity
Solitomab (MT110) Phase 1 • Relapse/refractory tumors Elevated hepatic enzymes, and diarrhea
Abbreviation: EpCAM: Epithelial cell adhesion molecule.

Volume 4 Issue 1 (2025) 7 doi: 10.36922/td.4926