EvolveImmune Therapeutics Initiates First-in-Human Trial of EVOLVE104 Trispecific T Cell Engager
核心洞察
EvolveImmune Therapeutics (搜索) has dosed the first patient in a Phase 1 clinical trial of EVOLVE104, marking the company's transition to clinical-stage status.
EVOLVE104 is a first-in-class trispecific T cell engager featuring integrated CD2 (搜索) costimulation that targets ULBP2/5/6 (搜索) antigens on solid tumors.
The Phase 1 study will enroll up to 160 patients with advanced urothelial and squamous cell carcinomas that are relapsed or refractory to standard therapies.
EvolveImmune Therapeutics (搜索) has achieved a significant milestone by dosing the first patient in a Phase 1 clinical trial of EVOLVE104, a novel trispecific T cell engager that represents the company's transition from preclinical to clinical-stage development. The first-in-human study, designated EIU-104101 (NCT07217171), is evaluating the safety, efficacy, and pharmacokinetics of EVOLVE104 in patients with advanced urothelial and squamous cell carcinomas.
Novel Trispecific Design Targets ULBP2/5/6 Antigens
EVOLVE104 distinguishes itself as a next-generation trispecific T cell engager featuring integrated CD2 (搜索) costimulation, making it the first molecule from EvolveImmune's proprietary EVOLVE platform to enter clinical development. The compound targets a novel set of tumor-associated antigens, ULBP2/5/6 (搜索), which are highly expressed on bladder cancer (搜索) and various squamous cell carcinomas while having limited expression in normal human tissues.
"By providing integrated costimulation through binding of CD3 (搜索) and CD2 (搜索), our EVOLVE T cell engagers have consistently outperformed bispecific T cell engagers in preclinical models, suggesting their potential to deliver best-in-class therapeutic activity to cancer patients," said Stephen Bloch, M.D., chief executive officer of EvolveImmune. "We are focused on advancing this innovation through clinical development with the goal of delivering a new class of T cell engager therapies to cancer patients who have few treatment options."
Notably, EVOLVE104 represents the first T cell-redirecting therapeutic candidate targeting ULBP2/5/6 (搜索) to enter clinical development, positioning it as a potential first-in-class treatment option.
Phase 1 Study Design and Patient Population
The newly initiated study will begin with a Phase 1a dose escalation portion, followed by Phase 1b dose expansion, and will enroll up to 160 subjects. The trial targets patients with locally advanced or metastatic bladder cancer (搜索), including urothelial and pure squamous histologies, as well as squamous cell carcinomas of the lung, esophagus, skin, tongue, and anogenital region that are relapsed from or refractory to standard of care therapies.
Preclinical Evidence Supports Clinical Advancement
In preclinical studies, EVOLVE104 demonstrated compelling single-agent activity and combination activity with anti-PD-1 therapy (搜索). The compound showed the ability to reinvigorate dysfunctional T cells and maintained a promising safety profile, providing the foundation for its advancement into human testing.
EVOLVE Platform Technology
EvolveImmune's proprietary EVOLVE platform is designed to therapeutically co-opt key mechanisms central to efficient immune synapse formation and T cell effector function. This approach aims to bypass low tumor immunogenicity, conditionally activate adaptive immunity, and reduce T cell dysfunction, allowing for amplified and sustained T cell tumor killing capacity to address unmet medical needs in solid tumors and hematologic malignancies.
The EVOLVE platform leverages integrated CD2 (搜索) costimulation to overcome therapeutic challenges of cancer cell resistance to current immunotherapies. EVOLVE molecules bind CD3 (搜索) and CD2 on T cells while simultaneously targeting tumor-associated antigens, creating a trispecific engagement mechanism that has shown superior performance compared to traditional bispecific approaches in preclinical models.
"The dosing of the first subject in our EVOLVE104 phase 1 trial represents a significant milestone for EvolveImmune, marking our transition to a clinical-stage biotechnology company," Bloch noted, emphasizing the company's evolution from a research-focused organization to one actively testing therapies in patients.