CAMBRIDGE, Mass.– Clasp Therapeutics has dosed the first patient in its Phase 1 clinical trial of CLSP-1025, a first-in-class T-cell engager (TCE) designed to target cancer cells with absolute specificity. The investigational therapy zeroes in on the p53R175H mutation, one of the most common cancer-driving mutations found in a range of solid tumors, including colorectal, lung, pancreatic, and gynecological cancers.
The trial, known as GUARDIAN-101, marks the first clinical evaluation of a tumor-specific TCE developed using Clasp’s proprietary pHLAre™ (precise HLA redirecting engager) platform. This technology is engineered to recognize tumor-specific peptides resulting from genetic mutations—such as p53R175H—rather than targeting proteins shared between cancerous and healthy cells, a limitation of earlier-generation TCEs.
“Treating the first patient in the GUARDIAN-101 trial is a significant milestone for Clasp and reinforces our mission to deliver highly precise immunotherapies for cancer,” said Dr. Lauren Harshman, senior vice president of clinical development at Clasp Therapeutics. “Advancing CLSP-1025 into clinical testing brings us closer to validating the potential of our pHLAre platform to offer safer, more effective treatment options.”
Mutations in the p53 gene, particularly the R175H variant, play a central role in cancer development and are considered truncal mutations—early events in tumor formation that persist across all cancer cells. By targeting these mutations, CLSP-1025 aims to direct the immune system to attack the tumor comprehensively while sparing normal tissues.
Clasp’s preclinical data, presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting, showed that CLSP-1025 demonstrated potent anti-tumor activity and a favorable safety profile, with strong selectivity and pharmacokinetic properties supporting its advancement into human trials.
The company’s pHLAre platform is designed to replicate the natural interface between a T cell receptor and a cancer cell, optimizing immune engagement and minimizing off-target effects—an issue that has challenged traditional T-cell engager therapies.
The GUARDIAN-101 trial will continue to assess the safety, tolerability, and initial efficacy of CLSP-1025 in patients with advanced solid tumors harboring the p53R175H mutation.
