Context Therapeutics (Nasdaq: CNTX) has registered a first-in-human Phase I clinical trial for CT-202, a Nectin-4 × CD3 bispecific T cell engaging antibody, in adults with recurrent or metastatic triple-negative breast cancer (TNBC), colorectal cancer, or urothelial cancer. The CT-202 clinical trial (NCT07545122) was posted to ClinicalTrials.gov on April 22, 2026, and marks the first time the molecule — originally developed by BioAtla (Nasdaq: BCAB) under the code BA3362 and in-licensed by Context in September 2024 for up to USD 133.5 million in total potential payments — will be administered to human subjects. CT-202 is a potential first-in-class agent in that no other Nectin-4-directed T cell engager has, to the knowledge available from the source material, reached clinical testing.
The Phase Ia/Ib study, designated NCT07545122, will enroll approximately 162 adults with Nectin-4-positive, treatment-refractory TNBC, colorectal cancer, or urothelial cancer, with a planned start date of September 2026 and primary completion targeted for Q1 2030. Phase Ia follows a Bayesian Optimal Interval (BOIN) dose-escalation design across approximately six dose levels administered every two weeks using a step-up priming strategy; the primary endpoint for this stage is the incidence of dose-limiting toxicities within the first 28 days of dosing. Phase Ib expands into up to six cohorts at two or more dose levels and schedules, with overall response rate by RECIST v1.1 as the primary endpoint. Patients must have received prior standard therapies and have measurable disease; a history of severe skin toxicity is grounds for exclusion, a criterion relevant given the dermatologic profile associated with Nectin-4-targeted agents.
Nectin-4 (PVRL4) is a cell-surface adhesion molecule overexpressed across urothelial, TNBC, and colorectal tumors relative to normal tissue, and its clinical tractability as an oncology target is already established through the approval of the antibody-drug conjugate enfortumab vedotin (Padcev; Astellas/Pfizer) in urothelial carcinoma. CT-202 pursues the same antigen through an orthogonal mechanism: rather than delivering a cytotoxic payload, it physically bridges Nectin-4-expressing tumor cells to CD3ε on cytotoxic T lymphocytes, forming an immune synapse that directs T cell-mediated lysis. The molecule incorporates BioAtla's proprietary Conditionally Active Biologic (CAB) platform, in which both the Nectin-4 and CD3 binding arms are engineered to activate preferentially in the acidic tumor microenvironment (approximately pH 6.0–6.5) rather than at normal physiological pH, a design intended to confine T cell engagement to the tumor site and reduce systemic toxicity. The CD3 arm is also functionally monovalent with a silenced Fc region, a configuration intended to prevent antigen-independent T cell activation and the cytokine release associated with earlier-generation CD3 bispecifics.
The most direct comparator in the Nectin-4 space is Astellas/Pfizer's Padcev (enfortumab vedotin), an antibody drug conjugate (ADC) currently approved for urothelial carcinoma and in trials across other Nectin-4-expressing tumors. CT-202 does not deliver a cytotoxic payload and therefore carries a mechanistically distinct toxicity hypothesis. A second contextual comparator is the class of approved CD3-engaging bispecifics in hematologic malignancies, where cytokine release syndrome has been a consistent management challenge. CT-202's dual pH-gating and monovalent CD3 design represent an attempt to address that liability in solid tumors, where the immunosuppressive microenvironment has historically blunted T cell engager activity.
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