One Bispecific Antibody-Drug Conjugate, Three Gateways: What a Dual-Target Oncology Candidate's Regulatory Path Reveals About Parallel Health Canada, FDA, and EMA Clinical Trial Authorization

Bispecific antibody-drug conjugates (ADCs) that simultaneously engage two distinct cell-surface receptors and deliver a cytotoxic payload represent one of the more structurally complex biologic modalities currently advancing through oncology development, combining the target-engagement logic of bispecific antibody engineering with the potency and bystander-effect considerations of conventional ADC payload chemistry. This article uses a hypothetical multicentre Phase 1b combination trial of a bispecific ADC candidate in recurrent or metastatic head and neck squamous cell carcinoma, sponsored by a fictional company, to compare the Clinical Trial Application (CTA) process required by Health Canada, the Investigational New Drug (IND) process required by the U.S. Food and Drug Administration, and the Clinical Trial Application process required by the European Medicines Agency under Regulation (EU) No 536/2014. The comparison traces how the Common Technical Document's harmonized Modules 2 through 5 carry the shared scientific case for a complex biologic across all three regions, while each jurisdiction's administrative layer, Module 1 in Canada and the United States, Part II of the EU's Clinical Trials Information System filing, imposes region-specific requirements that a sponsor developing a combination-therapy oncology program cannot simply duplicate from one region to the next. The article addresses the particular operational challenges this modality and combination-trial design create, the specific ways artificial intelligence tools are used, and can responsibly be used, in preparing and administering this kind of complex, multi-document regulatory package, and closes with recommendations for regulatory operations teams managing bispecific ADC programs across these three jurisdictions.Keywords: bispecific antibody-drug conjugate; oncology combination therapy; Clinical Trial Application; Investigational New Drug; Regulation (EU) No 536/2014; CTIS; regulatory artificial intelligence