Context Therapeutics Advances Two Bispecific T Cell Engagers with Promising Early Clinical and Preclinical Data at SITC 2025
Key Insights
Context Therapeutics presented data on CT-95 and CT-202 bispecific T cell engagers at SITC 2025, targeting mesothelin and Nectin-4 (search) respectively for solid tumor treatment.
CT-95 Phase 1 trial has enrolled 6 patients with no cytokine release syndrome (search) greater than Grade 2 and no dose-limiting toxicity observed to date.
CT-202 demonstrates best-in-class potential in preclinical studies with a favorable safety profile, expected to enter first-in-human trials in Q2 2026.
Context Therapeutics Inc. (Nasdaq: CNTX) presented encouraging clinical and preclinical data for two bispecific T cell engagers (TCEs) at the Society for Immunotherapy of Cancer's 40th Annual Meeting in National Harbor, Maryland. The Philadelphia-based clinical-stage biopharmaceutical company showcased progress on CT-95, a mesothelin-targeting therapy currently in Phase 1 trials, and CT-202, a Nectin-4 (search)-directed candidate preparing for clinical entry.
CT-95 Demonstrates Favorable Safety Profile in Ongoing Phase 1 Trial
CT-95, a mesothelin x CD3 (search) bispecific TCE, has enrolled 6 patients as of October 30, 2025, in its ongoing Phase 1 dose-escalation study. The trial is currently enrolling Cohort 3 with a priming dose of 0.18 μg/kg and a full dose of 0.6 μg/kg. Notably, no cytokine release syndrome (search) (CRS) greater than Grade 2 has been observed across any cohort, and no dose-limiting toxicity (DLT) has occurred. The maximum tolerated dose (MTD) has not been reached, supporting continued dose escalation toward target levels.
Based on preclinical projections, CT-95 is expected to achieve target dose exposure starting at Cohort 4. Context Therapeutics anticipates providing initial Phase 1a data in mid-2026, representing a key milestone for the program.
The therapy addresses a significant challenge in mesothelin-targeted drug development. Mesothelin is overexpressed in approximately 30% of cancers, but therapeutic development has been complicated by shed mesothelin fragments in blood and the tumor microenvironment that act as decoys for targeting antibodies. CT-95 is engineered as a fully humanized bispecific with moderate affinity but high avidity for membrane-bound mesothelin, designed to minimize interference from these shed fragments.
CT-202 Shows Best-in-Class Potential in Preclinical Studies
CT-202, a Nectin-4 (search) x CD3 (search) bispecific TCE, demonstrated potent preclinical activity with a favorable pharmacokinetic and safety profile. The preclinical data supports what the company describes as best-in-class potential for this candidate. Context expects to complete necessary regulatory filings to support initiation of a first-in-human trial in the second quarter of 2026.
Nectin-4 (search) represents a clinically validated target highly and frequently overexpressed across various solid tumors (search), including bladder, colorectal, lung, and breast cancers. While traditional antibody-drug conjugates (ADCs) targeting Nectin-4 have shown efficacy, they are associated with adverse events including neuropathy and rash. CT-202 is engineered as a pH-dependent TCE designed for preferential activity within the acidic tumor microenvironment, potentially improving selectivity and reducing off-target toxicity.
Expanding TCE Portfolio for Solid Tumors
Context Therapeutics is building a portfolio of TCE bispecific therapeutics that includes CTIM-76 (Claudin 6 (search) x CD3 (search)), CT-95 (Mesothelin x CD3), and CT-202 (Nectin-4 (search) x CD3). The company's approach focuses on T cell engaging bispecific antibodies specifically designed for solid tumors (search), an area where traditional immunotherapies have faced significant challenges.
The CT-95 clinical trial (NCT06756035) is being conducted at clinical sites across the United States. Both CT-95 and CT-202 incorporate innovative design features intended to enhance therapeutic activity while minimizing systemic toxicity - CT-95 through its avidity-enhanced, affinity-tuned approach to overcome shed antigen interference, and CT-202 through pH-dependent activation for tumor-selective activity.