ETBX-011 (Ad5 [E1-, E2b-]-CEA): A Comprehensive Review of an Adenoviral Vector-Based Cancer Vaccine

Executive Summary

ETBX-011 (DrugBank ID: DB17464) is an investigational, second-generation therapeutic cancer vaccine designed to elicit a targeted immune response against tumors expressing the carcinoembryonic antigen (CEA). Developed initially by Etubics Corporation and later integrated into the ImmunityBio, Inc. pipeline, ETBX-011 is built upon a sophisticated adenoviral vector platform (Ad5 [E1-, E2b-]) engineered to overcome the challenge of pre-existing anti-vector immunity, a significant limitation of earlier viral vector-based therapies. This platform has demonstrated a consistent and favorable safety profile across multiple clinical trials, successfully inducing robust, antigen-specific T-cell responses in patients with advanced cancers.

The core mechanism of action involves using a replication-incompetent adenovirus to deliver the genetic code for a modified, highly immunogenic form of CEA into host cells, primarily antigen-presenting cells. This triggers the host's immune system to recognize CEA as a foreign threat, generating cytotoxic T-lymphocytes that can seek out and destroy CEA-expressing cancer cells. To combat tumor heterogeneity, ETBX-011 was frequently evaluated as part of a multi-antigen "Tri-Ad5" regimen, co-administered with vaccines targeting MUC1 (ETBX-061) and brachyury (ETBX-051).

Early clinical development showed considerable promise. A Phase 1/2 trial of ETBX-011 monotherapy in heavily pre-treated metastatic colorectal cancer (mCRC) patients demonstrated encouraging signals of clinical activity, with a median overall survival of 11 months and durable immune responses. Subsequent Phase 1 trials of the Tri-Ad5 combination confirmed its safety and ability to induce T-cell responses against all three target antigens without evidence of antigenic competition.