CLSP-1025 / Clasp Therapeutics - LARVOL DELTA

Preclinical characterization of CLSP-1025, a first-in-class, mutation-specific T-cell engager targeting a neoantigen derived from a common p53 mutation. (PubMed, Clin Cancer Res) - "These data establish CLSP-1025 as a highly selective, mutation-specific T-cell engager and support the feasibility of targeting shared intracellular neoantigens with pHLA-directed immunotherapies. This favorable preclinical activity and specificity support ongoing clinical investigation of CLSP-1025 in HLA-A*02:01+ patients with cancers harboring p53R175H and outline a framework for developing next-generation TCEs against additional driver mutations."

IO biomarker • Journal • P53mut • Preclinical • Oncology • CD4 • CD8 • HLA-A • TP53

CLSP-1025, a first-in-class precision T cell engager for the treatment of p53 mutant cancers (AACR 2025) - "The population frequency of HLA-A*02:01 in the US is ~41% (Gragert 2013).A mechanistically based, CLSP-1025-specific quantitative systems pharmacology (QSP) model incorporating target binding affinities, CD3 receptor occupancy, in vitro pharmacodynamics, and in vivo rodent PK profiles was developed to predict an efficacious dose range to inform the FIH study. The model predicted a terminal half-life for CLSP-1025 of approximately 16 days and the potential for tumor regression at target peptide-HLA densities as low as 2 molecules/cell.Clinical evaluation of CLSP-1025 will be initiated in early 2025 in the GUARDIAN-101 study, a FIH dose escalation and expansion trial to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of CLSP-1025 in HLA-A*02:01 positive patients with advanced solid tumors harboring the p53 R175H mutation."

First-in-human • P53mut • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Solid Tumor • HLA-A • TP53

GUARDIAN-101: A first in human, tumor agnostic phase I study evaluating safety and preliminary antitumor activity of CLSP-1025, a first in class, HLA-directed T cell engager (TCE) for advanced solid tumors harboring the p53 R175H mutation (ESMO 2025) - P1 | "Longitudinal ctDNA monitoring will track response kinetics and resistance evolution with correlative analyses to tissue NGS. Enrollment began April 2025."

Clinical • First-in-human • Metastases • P1 data • Pan tumor • Colorectal Cancer • Oncology • Solid Tumor • HLA-A • TP53

Clasp Therapeutics Doses First Patient in Phase 1 Clinical Trial With a First-in-Class T-Cell Engager Designed to Target Cancer Cells With Absolute Specificity (Businesswire) - "Clasp Therapeutics...announced dosing of the initial patient in the GUARDIAN-101 phase 1 trial of CLSP-1025, the first tumor-specific TCE to enter clinical development....At the 2025 American Association for Cancer Research (AACR) Annual Meeting this week, Clasp also presented nonclinical data supporting the clinical development of CLSP-1025, including data supporting the therapeutic candidate’s selectivity, activity, pharmacokinetics and safety profile."

Preclinical • Trial status • Bladder Cancer • Breast Cancer • Colorectal Cancer • Lung Cancer • Ovarian Cancer • Pancreatic Adenocarcinoma • Prostate Cancer • Squamous Cell Carcinoma of Head and Neck

GUARDIAN-101: A Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Clasp Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TP53

GUARDIAN-101: A Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation (clinicaltrials.gov) - P1 | N=90 | Not yet recruiting | Sponsor: Clasp Therapeutics, Inc.

New P1 trial • Bladder Cancer • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TP53

CLSP-1025, a novel bispecific T-cell engager targeting a p53 R175H mutant peptide presented by HLA-A*02:01 (SITC 2024) - "An IND application filing is planned for Q4 of 2024. Ethics Approval All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of Charles River Accelerator and Development Labs."

Oncology • Solid Tumor • HLA-A • TP53

Clasp Therapeutics Presents Comprehensive Preclinical Data Validating First-in-Class Precision T Cell Engager Against p53 Mutant Solid Tumors at SITC Annual Meeting (Businesswire) - "Clasp Therapeutics...announced new data validating the potential of its lead program, CLSP-1025. CLSP-1025 is a half-life extended TCE targeting cancer cells expressing the p53R175H mutant peptide presented by HLA-A*02:01....Data Highlights:...Sensitivity: CLSP-1025 activates T cells and effectively kills patient-derived organoids, demonstrating activity at endogenous target expression levels; Activity: CLSP-1025 induces the regression of established tumors in vivo."

Preclinical • Solid Tumor

Clasp Therapeutics to Present Preclinical Data Evaluating Novel T Cell Engager Targeting p53 Mutant Solid Tumors (Businesswire) - "Clasp Therapeutics, a biotechnology company bringing unparalleled precision to immuno-oncology using next-generation T cell engagers (TCEs), today announced it will present comprehensive preclinical data demonstrating the selectivity and activity of CLSP-1025, a TCE targeting a common p53 mutation, at the 2024 Annual Meeting of the Society for Immunotherapy of Cancer (SITC), being held November 8 - 10, 2024 in Houston, Texas and virtually."

Preclinical • Oncology • Solid Tumor