A Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation (GUARDIAN-101)

Clasp Therapeutics, Inc.

Status and phase: Enrolling; Phase 1

Conditions: Breast Cancer; Colorectal Adenocarcinoma; Bladder Cancer; Unresectable Solid Tumor; Pancreatic Adenocarcinoma; Advanced Solid Tumor; Lung Cancer; Ovarian Cancer; Prostate Cancer; Metastatic Solid Tumor; Head and Neck Squamous Cell Carcinoma

Treatments: Drug: CLSP-1025

Study type: Interventional

Funder types: Industry

Identifiers

NCT06778863

CLSP-1025-101

Details and patient eligibility

About

Phase 1 dose escalation and expansion study of CLSP-1025, a first-in-class HLA-A*02:01 specific T cell engager (TCE) targeting solid tumors that harbor the p53 R175H mutation.

Full description

This Phase 1, open-label, multicenter study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of CLSP-1025 when administered to HLA-A*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation. The study will be conducted in 2 parts: Part A Monotherapy Dose Escalation to determine the recommended dose(s) for expansion (RDE[s]) and Part B Monotherapy Expansion to explore the preliminary antitumor activity as well as further characterize the safety, tolerability, PK, and PD of CLSP-1025 at the RDE(s).

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Patients must be at least 18 years of age at the time of signing the informed consent.
• Patients must be willing and able to provide written informed consent
• Patients must have locally advanced or metastatic solid tumors that have progressed after standard of care therapy or for which no standard therapy exists
• Tumors must harbor a TP53 R175H variant mutation confirmed by an accredited laboratory-based test
• Patients must be HLA-A*02:01 positive by central assay
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of enrollment
• Adequate hematological, renal and hepatic function
• Per Investigator judgement, patient is willing and able to complete study visits and/or procedures per the protocol and comply with study requirements for study participation

Key Exclusion Criteria:

• Patients with Li-Fraumeni syndrome or other known germline p53 R175H mutation
• Patients who have received other p53 R175H-directed therapies
• Patients who have not fully recovered from adverse events due to previous anticancer therapies
• Patients with active infection requiring systemic antimicrobial therapy
• Any other primary malignancy within the 2 years prior to enrollment (except for non- melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast) or prostate cancer in remission.
• Known active central nervous system metastases and/or carcinomatous meningitis

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

90 participants in 2 patient groups

Part A: Monotherapy Dose Escalation of CLSP-1025

Experimental group

Description:

Dose escalation of CLSP-1025 in HLA-A\*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation

Treatment:

Drug: CLSP-1025

Part B: Monotherapy Dose Expansion of CLSP-1025

Experimental group

Description:

Dose expansion of CLSP-1025 in HLA-A\*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation

Treatment:

Drug: CLSP-1025